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Successful oral peptide delivery faces two major hurdles: low enzymatic stability in the gastro-intestinal lumen and poor intestinal membrane permeability. While lipid-based formulations (LBF) have the potential to overcome these barriers, effective formulation of peptides remains challenging. Lipophilic salt (LS) technology can increase the apparent lipophilicity of peptides, making them more suitable for LBF. As a model therapeutic peptide, octreotide (OCT) was converted to the docusate LS (OCT.DoS2), and compared to the commercial acetate salt (OCT.OAc2) in oral absorption studies and related in vitro studies, including parallel artificial membrane permeability assay (PAMPA), Caco-2, in situ intestine perfusion, and simulated digestion in vitro models. The in vivo oral absorption of OCT.DoS2 and OCT.OAc2 formulated in self-emulsifying drug delivery systems (SEDDS) was studied in rats. LS formulation improved the solubility and loading of OCT in LBF excipients and OCT.DoS2 in combination with SEDDS showed higher OCT absorption than the acetate comparator in the in vivo studies in rats. The Caco-2 and in situ intestine perfusion models indicated no increases in permeability for OCT.DoS2. However, the in vitro digestion studies showed reduced enzymatic degradation of OCT.DoS2 when formulated in the SEDDS formulations. Further in vitro dissociation and release studies suggest that the enhanced bioavailability of OCT from SEDDS-incorporating OCT.DoS2 is likely a result of higher partitioning into and prolonged retention within lipid colloid structures. The combination of LS and LBF enhanced the in vivo oral absorption of OCT primarily via the protective effect of LBF sheltering the peptide from gastrointestinal degradation.
Peng Li; Leigh Ford; Shadabul Haque; Mitchell P. McInerney; Hywel D. Williams; Peter J. Scammells; Philip E. Thompson; Vincent Jannin; Christopher J. H. Porter; Hassan Benameur; Colin W. Pouton. Lipophilic Salts and Lipid-Based Formulations: Enhancing the Oral Delivery of Octreotide. Pharmaceutical Research 2021, 38, 1125 -1137.
AMA StylePeng Li, Leigh Ford, Shadabul Haque, Mitchell P. McInerney, Hywel D. Williams, Peter J. Scammells, Philip E. Thompson, Vincent Jannin, Christopher J. H. Porter, Hassan Benameur, Colin W. Pouton. Lipophilic Salts and Lipid-Based Formulations: Enhancing the Oral Delivery of Octreotide. Pharmaceutical Research. 2021; 38 (6):1125-1137.
Chicago/Turabian StylePeng Li; Leigh Ford; Shadabul Haque; Mitchell P. McInerney; Hywel D. Williams; Peter J. Scammells; Philip E. Thompson; Vincent Jannin; Christopher J. H. Porter; Hassan Benameur; Colin W. Pouton. 2021. "Lipophilic Salts and Lipid-Based Formulations: Enhancing the Oral Delivery of Octreotide." Pharmaceutical Research 38, no. 6: 1125-1137.
The aim of this study was to evaluate the effect of lipid digestion on the permeability and absorption of orally administered saquinavir (SQV), a biopharmaceutics classification system (BCS) class IV drug, in different lipid-based formulations. Three LBFs were prepared: a mixed short- and medium-chain lipid-based formulation (SMCF), a medium-chain lipid-based formulation (MCF), and a long-chain lipid-based formulation (LCF). SQV was loaded into these LBFs at 26.7 mg/g. To evaluate the pharmacokinetics of SQV in vivo, drug-loaded formulations were predispersed in purified water at 3% w/w and orally administered to rats. A low dose (0.8 mg/rat) was employed to limit confounding effects on drug solubilization, and consistent with this design, presolubilization of SQV in the LBFs did not increase in vivo exposure compared to a control suspension formulation. The areas under the plasma concentration–time curve were, however, significantly lower after administration of SQV as MCF and LCF compared to SMCF. To evaluate the key mechanisms underpinning absorption, each LBF containing SQV was digested, and the flux of SQV from the digests across a dialysis membrane was evaluated in in vitro permeation experiments. This study revealed that the absorption profiles were driven by the free concentration of SQV and that this varied due to differences in SQV solubilization in the digestion products generated by LBF digestion. The apparent first-order permeation rate constants of SQV (kapp,total) were estimated by dividing the flux of SQV in the dialysis membrane experiments by the concentration of total SQV on the donor side. kapp,total values strongly correlated with in vivo AUC. The data provide one of the first studies of the effect of digestion products on the free concentration of a drug in the GI fluid and oral absorption. This simple permeation model may be a useful tool for the evaluation of the impact of lipid digestion on apparent drug permeability from lipid-based formulations. These effects should be assessed alongside, and in addition to, the more well-known effects of lipids on enhancing intestinal solubilization of poorly water-soluble drugs.
Yusuke Tanaka; Tri-Hung Nguyen; Estelle J. A. Suys; Christopher J. H. Porter. Digestion of Lipid-Based Formulations Not Only Mediates Changes to Absorption of Poorly Soluble Drugs Due to Differences in Solubilization But Also Reflects Changes to Thermodynamic Activity and Permeability. Molecular Pharmaceutics 2021, 18, 1768 -1778.
AMA StyleYusuke Tanaka, Tri-Hung Nguyen, Estelle J. A. Suys, Christopher J. H. Porter. Digestion of Lipid-Based Formulations Not Only Mediates Changes to Absorption of Poorly Soluble Drugs Due to Differences in Solubilization But Also Reflects Changes to Thermodynamic Activity and Permeability. Molecular Pharmaceutics. 2021; 18 (4):1768-1778.
Chicago/Turabian StyleYusuke Tanaka; Tri-Hung Nguyen; Estelle J. A. Suys; Christopher J. H. Porter. 2021. "Digestion of Lipid-Based Formulations Not Only Mediates Changes to Absorption of Poorly Soluble Drugs Due to Differences in Solubilization But Also Reflects Changes to Thermodynamic Activity and Permeability." Molecular Pharmaceutics 18, no. 4: 1768-1778.
Heightened expression of human endogenous retrovirus (HERV) sequences has been associated with a range of malignancies, including prostate cancer, suggesting that they may serve as useful diagnostic or prognostic cancer biomarkers. We analysed the expression of HERV-K (Gag and Env/Np9 regions), HERV-E 4.1 (Pol and Env regions), HERV-H (Pol) and HERV-W (Gag) sequences in prostate cancer cells lines and normal prostate epithelial cells using qRT-PCR. HERV expression was also analysed in matched malignant and benign prostate tissue samples from men with prostate cancer (n = 27, median age 65.2 years (range 47–70)) and compared to prostate cancer-free male controls (n = 11). Prostate cancer epithelial cell lines exhibited a signature of HERV RNA overexpression, with all HERVs analysed, except HERV-E Pol, showing heightened expression in at least two, but more commonly all, cell lines analysed. Analysis of primary prostate material indicated increased expression of HERV-E Pol but decreased expression of HERV-E Env in both malignant and benign regions of the prostate in men with prostate cancer as compared to those without. Expression of HERV-K Gag was significantly higher in malignant regions of the prostate in men with prostate cancer as compared to matched benign regions and prostate cancer-free men (p < 0.001 for both), with 85.2% of prostate cancers donors showing malignancy-associated upregulation of HERV-K Gag RNA. HERV-K Gag protein was detected in 12/18 (66.7%) malignant tissues using immunohistochemistry, but only 1/18 (5.6%) benign tissue sections. Heightened expression of HERV-K Gag RNA and protein appears to be a sensitive and specific biomarker of prostate malignancy in this cohort of men with prostate carcinoma, supporting its potential utility as a non-invasive, adjunct clinical biomarker.
Simin Rezaei; Joshua Hayward; Sam Norden; John Pedersen; John Mills; Anna Hearps; Gilda Tachedjian. HERV-K Gag RNA and Protein Levels Are Elevated in Malignant Regions of the Prostate in Males with Prostate Cancer. Viruses 2021, 13, 449 .
AMA StyleSimin Rezaei, Joshua Hayward, Sam Norden, John Pedersen, John Mills, Anna Hearps, Gilda Tachedjian. HERV-K Gag RNA and Protein Levels Are Elevated in Malignant Regions of the Prostate in Males with Prostate Cancer. Viruses. 2021; 13 (3):449.
Chicago/Turabian StyleSimin Rezaei; Joshua Hayward; Sam Norden; John Pedersen; John Mills; Anna Hearps; Gilda Tachedjian. 2021. "HERV-K Gag RNA and Protein Levels Are Elevated in Malignant Regions of the Prostate in Males with Prostate Cancer." Viruses 13, no. 3: 449.
The mesenteric lymph nodes (MLN) are a key site for the generation of adaptive immune responses to gut-derived antigenic material and immune cells within the MLN contribute to the pathophysiology of a range of conditions including inflammatory and autoimmune diseases, viral infections, graft versus host disease and cancer. Targeting immunomodulating drugs to the MLN may thus be beneficial in a range of conditions. This paper investigates the potential benefit of targeting a model immunosuppressant drug, mycophenolic acid (MPA), to T cells in the MLN, using a triglyceride (TG) mimetic prodrug approach. We confirmed that administration of MPA in the TG prodrug form (MPA-TG), increased lymphatic transport of MPA-related species 83-fold and increased MLN concentrations of MPA >20 fold, when compared to MPA alone, for up to 4 h in mice. At the same time, the plasma exposure of MPA and MPA-TG was similar, limiting the opportunity for systemic side effects. Confocal microscopy and flow cytometry studies with a fluorescent model prodrug (Bodipy-TG) revealed that the prodrug accumulated in the MLN cortex and paracortex at 5 and 10 h following administration and was highly associated with B cells and T cells that are found in these regions of the MLN. Finally, we demonstrated that MPA-TG was significantly more effective than MPA at inhibiting CD4+ and CD8+ T cell proliferation in the MLN of mice in response to an oral ovalbumin antigen challenge. In contrast, MPA-TG was no more effective than MPA at inhibiting T cell proliferation in peripheral LN when mice were challenged via SC administration of ovalbumin. This paper provides the first evidence of an in vivo pharmacodynamic benefit of targeting the MLN using a TG mimetic prodrug approach. The TG mimetic prodrug technology has the potential to benefit the treatment of a range of conditions where aberrant immune responses are initiated in gut-associated lymphoid tissues.
Ruby Kochappan; Enyuan Cao; Sifei Han; Luojuan Hu; Tim Quach; Danielle Senyschyn; Vilena Ivanova Ferreira; Given Lee; Nathania Leong; Garima Sharma; Shea Fern Lim; Cameron J. Nowell; Ziqi Chen; Ulrich H. von Andrian; Daniel Bonner; Justine D. Mintern; Jamie S. Simpson; Natalie L. Trevaskis; Christopher J.H. Porter. Targeted delivery of mycophenolic acid to the mesenteric lymph node using a triglyceride mimetic prodrug approach enhances gut-specific immunomodulation in mice. Journal of Controlled Release 2021, 332, 636 -651.
AMA StyleRuby Kochappan, Enyuan Cao, Sifei Han, Luojuan Hu, Tim Quach, Danielle Senyschyn, Vilena Ivanova Ferreira, Given Lee, Nathania Leong, Garima Sharma, Shea Fern Lim, Cameron J. Nowell, Ziqi Chen, Ulrich H. von Andrian, Daniel Bonner, Justine D. Mintern, Jamie S. Simpson, Natalie L. Trevaskis, Christopher J.H. Porter. Targeted delivery of mycophenolic acid to the mesenteric lymph node using a triglyceride mimetic prodrug approach enhances gut-specific immunomodulation in mice. Journal of Controlled Release. 2021; 332 ():636-651.
Chicago/Turabian StyleRuby Kochappan; Enyuan Cao; Sifei Han; Luojuan Hu; Tim Quach; Danielle Senyschyn; Vilena Ivanova Ferreira; Given Lee; Nathania Leong; Garima Sharma; Shea Fern Lim; Cameron J. Nowell; Ziqi Chen; Ulrich H. von Andrian; Daniel Bonner; Justine D. Mintern; Jamie S. Simpson; Natalie L. Trevaskis; Christopher J.H. Porter. 2021. "Targeted delivery of mycophenolic acid to the mesenteric lymph node using a triglyceride mimetic prodrug approach enhances gut-specific immunomodulation in mice." Journal of Controlled Release 332, no. : 636-651.
Lipid based formulations (LBFs) can enhance oral bioavailability, however, their utility may be restricted by low drug loading in the formulation. Converting drugs to drug-ionic liquids (drug-ILs) or lipophilic salts can significantly increase lipid solubility but this approach is complicated in some cases by salt disproportionation, leading to a reduction in solubility and physical instability. Here we explore the physical stability of the weakly basic model drug, cinnarizine (CIN), when paired with a decanoate counterion (Dec) to form the drug-IL, cinnarizine decanoate (CIN.Dec). Consistent with published studies of salt disproportionation in aqueous solution, weakly acidic counterions such as Dec lead to the generation of drug-IL lipid solutions with pHs below pHmax. This leads to CIN deprotonation to the less soluble free base and precipitation. Subsequent studies however, show that these effects can be reversed by acidification of the formulation (either with excess decanoic acid or other lipid soluble acids), stimulating a pH shift to the salt plateau of CIN.Dec and the formation of stable lipid solutions of CIN.Dec. Altering formulation pH to more acidic conditions, therefore stabilises drug-ILs formed using weakly acidic lipophilic counterions, and is a viable method to promote formulation stability via inhibition of disproportionation of some drug-ILs.
Anthony Lai; Yasemin Sahbaz; Leigh Ford; Tri-Hung Nguyen; Shadabul Haque; Hywel D. Williams; Hassan Benameur; Peter J. Scammells; Christopher J.H. Porter. Stabilising disproportionation of lipophilic ionic liquid salts in lipid-based formulations. International Journal of Pharmaceutics 2021, 597, 120292 .
AMA StyleAnthony Lai, Yasemin Sahbaz, Leigh Ford, Tri-Hung Nguyen, Shadabul Haque, Hywel D. Williams, Hassan Benameur, Peter J. Scammells, Christopher J.H. Porter. Stabilising disproportionation of lipophilic ionic liquid salts in lipid-based formulations. International Journal of Pharmaceutics. 2021; 597 ():120292.
Chicago/Turabian StyleAnthony Lai; Yasemin Sahbaz; Leigh Ford; Tri-Hung Nguyen; Shadabul Haque; Hywel D. Williams; Hassan Benameur; Peter J. Scammells; Christopher J.H. Porter. 2021. "Stabilising disproportionation of lipophilic ionic liquid salts in lipid-based formulations." International Journal of Pharmaceutics 597, no. : 120292.
Aim: Delivery of nanoparticles (NPs) to tumors can be impeded by high levels of hyaluronan (HA) in the stroma. Enzymatic depolymerization of HA with PEGylated hyaluronidase (PEGPH20) improves the delivery of antibodies to tumors. However, it is unknown whether NP delivery is enhanced by this strategy. Methods: The impact of PEGPH20 pretreatment on the uptake and tumor penetration of model PEGylated polystyrene NPs was studied in mice with orthotopic breast cancers. Results: Tumor oxygenation and NP penetration, but not overall tumor uptake, of 50 nm NPs, was significantly enhanced by PEGPH20 pre-administration. Conclusion: PEGPH20 has the potential to improve intratumoral penetration of NP-based drug delivery systems and enhance access to cancer cells in poorly vascularized regions of the tumor.
Daniel Hs Brundel; Orlagh M Feeney; Cameron J Nowell; Estelle Ja Suys; Gracia Gracia; Lisa M Kaminskas; Michelle M McIntosh; David W Kang; Christopher Jh Porter. Depolymerization of hyaluronan using PEGylated human recombinant hyaluronidase promotes nanoparticle tumor penetration. Nanomedicine 2021, 16, 275 -292.
AMA StyleDaniel Hs Brundel, Orlagh M Feeney, Cameron J Nowell, Estelle Ja Suys, Gracia Gracia, Lisa M Kaminskas, Michelle M McIntosh, David W Kang, Christopher Jh Porter. Depolymerization of hyaluronan using PEGylated human recombinant hyaluronidase promotes nanoparticle tumor penetration. Nanomedicine. 2021; 16 (4):275-292.
Chicago/Turabian StyleDaniel Hs Brundel; Orlagh M Feeney; Cameron J Nowell; Estelle Ja Suys; Gracia Gracia; Lisa M Kaminskas; Michelle M McIntosh; David W Kang; Christopher Jh Porter. 2021. "Depolymerization of hyaluronan using PEGylated human recombinant hyaluronidase promotes nanoparticle tumor penetration." Nanomedicine 16, no. 4: 275-292.
Drug absorption from lipid-based formulations (LBFs) in the gastrointestinal (GI) tract is the result of a series of processes, including formulation dispersion, interaction with biliary and pancreatic secretions, drug solubilisation and supersaturation, and finally intestinal permeability. Optimal formulation design is dependent on a good understanding of the limitations to, and drivers of, absorption, but for LBFs the complexity of these processes makes data interpretation complex. The current study has re-examined a previous in vitro digestion–in situ perfusion model to increase physiological relevance and has used this model to examine drug absorption from LBFs. The composition of rat bile and jejunal fluid was also characterised to identify in vivo-relevant conditions. Digestion was initiated using rat bile/pancreatic fluid and the formulation and digestive enzymes mixed immediately prior to entry into the jejunum (allowing dilution/digestion to occur at the absorptive site). These conditions were employed to study drug absorption from LBFs of high (fenofibrate, FFB) and low (saquinavir, SQV) permeability compounds. The impact of polymeric precipitation inhibitors (PPIs) was also evaluated. For FFB, supersaturation, initiated by formulation interaction with biliary/pancreatic fluids, appeared to drive absorption and the addition of the PPIs poly(glycidyl methacrylate) (PPGAE) and hydroxypropylmethyl cellulose (HPMC), reduced drug precipitation, increased FFB supersaturation and increased absorption from a Type IV LBF of FFB. For a Type IIIB LBF however, PPIs were ineffective at increasing absorption. The impact of PPIs on the absorption of a less permeable drug, SQV, was similarly evaluated and again drug absorption appeared to be related to the extent of supersaturation, although in this case PPI were unable to promote absorption. For both FFB and SQV, drug absorption patterns obtained with the in vitro digestion–in situ perfusion mode, correlated well with in vitro supersaturation data and in vivo drug exposure data from oral bioavailability studies. The data are consistent with a mode of drug absorption where rapid dilution of LBFs with biliary and pancreatic secretions at the absorptive site in the upper small intestine drives transient supersaturation, that supersaturation is a significant driver of drug absorption for both low and high permeability drugs, and that PPIs delay drug precipitation, enhance supersaturation and promote drug absorption in a drug and formulation specific manner.
Estelle J.A. Suys; Daniel H.S. Brundel; David K. Chalmers; Colin W. Pouton; Christopher J.H. Porter. Interaction with biliary and pancreatic fluids drives supersaturation and drug absorption from lipid-based formulations of low (saquinavir) and high (fenofibrate) permeability poorly soluble drugs. Journal of Controlled Release 2021, 331, 45 -61.
AMA StyleEstelle J.A. Suys, Daniel H.S. Brundel, David K. Chalmers, Colin W. Pouton, Christopher J.H. Porter. Interaction with biliary and pancreatic fluids drives supersaturation and drug absorption from lipid-based formulations of low (saquinavir) and high (fenofibrate) permeability poorly soluble drugs. Journal of Controlled Release. 2021; 331 ():45-61.
Chicago/Turabian StyleEstelle J.A. Suys; Daniel H.S. Brundel; David K. Chalmers; Colin W. Pouton; Christopher J.H. Porter. 2021. "Interaction with biliary and pancreatic fluids drives supersaturation and drug absorption from lipid-based formulations of low (saquinavir) and high (fenofibrate) permeability poorly soluble drugs." Journal of Controlled Release 331, no. : 45-61.
This year marked the fifth meeting of the International Workshop on Microbiome in HIV held at the NIH1-4. In the past year, appreciation for the interplay between the human microbiome and HIV infection has continued to grow. New studies presented here help clarify the role of the microbiome on chronic inflammation and vaccine design and reveal the interaction between the effects of genetics, environment, sexual practice and HIV infection on the microbiome. Further, reports on the development and clinical trials of microbiome-based therapeutic approaches investigate the potential of microbiome alterations to decrease the probability of acquisition/transmission or ameliorate sequellae of HIV. Essential to all studies is the continued development and standardization of best methods for data analysis and consistency across studies and approaches. The keynote address by Dr. Jacques Ravel focused on his work to improve the analysis and resolution of microbiome data.
Scott Sherrill-Mix; Kaleigh Connors; Grace M. Aldrovandi; Jason M. Brenchley; Charles Boucher; Frederic D. Bushman; Ronald G. Collman; Satya Dandekar; Nichole R. Klatt; Laurel A. Lagenaur; Roger Paredes; Gilda Tachedjian; Jim A. Turpin; Alan L. Landay; Mimi Ghosh. A Summary of the Fifth Annual Virology Education HIV Microbiome Workshop. AIDS Research and Human Retroviruses 2020, 36, 886 -895.
AMA StyleScott Sherrill-Mix, Kaleigh Connors, Grace M. Aldrovandi, Jason M. Brenchley, Charles Boucher, Frederic D. Bushman, Ronald G. Collman, Satya Dandekar, Nichole R. Klatt, Laurel A. Lagenaur, Roger Paredes, Gilda Tachedjian, Jim A. Turpin, Alan L. Landay, Mimi Ghosh. A Summary of the Fifth Annual Virology Education HIV Microbiome Workshop. AIDS Research and Human Retroviruses. 2020; 36 (11):886-895.
Chicago/Turabian StyleScott Sherrill-Mix; Kaleigh Connors; Grace M. Aldrovandi; Jason M. Brenchley; Charles Boucher; Frederic D. Bushman; Ronald G. Collman; Satya Dandekar; Nichole R. Klatt; Laurel A. Lagenaur; Roger Paredes; Gilda Tachedjian; Jim A. Turpin; Alan L. Landay; Mimi Ghosh. 2020. "A Summary of the Fifth Annual Virology Education HIV Microbiome Workshop." AIDS Research and Human Retroviruses 36, no. 11: 886-895.
Drug delivery to the lymphatic system is gaining increasing attention, particularly in fields such as immunotherapy where drug access to lymphocytes is central to activity. We have previously described a prodrug strategy that facilitates the lymphatic delivery of a model immunomodulator, mycophenolic acid (MPA) via incorporation into intestinal triglyceride transport pathways. The current study explored a series of structurally related glyceride and phospholipid mimetic prodrugs of MPA in an attempt to enhance lymph targeting and to better elucidate the design criteria for lipid mimetic prodrugs. MPA was conjugated to a glyceride or phospholipid backbone at various positions using different spacers employing ester, ether, carbonate and amide bonds. Patterns of prodrug hydrolysis were evaluated in rat digestive fluid, and lymphatic transport and plasma pharmacokinetics were assessed in lymph duct cannulated rats. Prodrugs with different spacers between MPA and the glyceride backbone resulted in up to 70-fold differences in gastrointestinal stability. MPA conjugation at the 2 position of the glyceride backbone and via an ester bond were most effective in promoting lymphatic transport. Phospholipid prodrug derivatives, or glyceride derivatives with MPA attached at the 1 position or when linked via ether, carbonate or amide bonds were poorly incorporated into lymphatic transport pathways.
Sifei Han; Tim Quach; Luojuan Hu; Shea Fern Lim; Gracia Gracia; Natalie L. Trevaskis; Jamie S. Simpson; Christopher J.H. Porter. The Impact of Conjugation Position and Linker Chemistry on the Lymphatic Transport of a Series of Glyceride and Phospholipid Mimetic Prodrugs. Journal of Pharmaceutical Sciences 2020, 110, 489 -499.
AMA StyleSifei Han, Tim Quach, Luojuan Hu, Shea Fern Lim, Gracia Gracia, Natalie L. Trevaskis, Jamie S. Simpson, Christopher J.H. Porter. The Impact of Conjugation Position and Linker Chemistry on the Lymphatic Transport of a Series of Glyceride and Phospholipid Mimetic Prodrugs. Journal of Pharmaceutical Sciences. 2020; 110 (1):489-499.
Chicago/Turabian StyleSifei Han; Tim Quach; Luojuan Hu; Shea Fern Lim; Gracia Gracia; Natalie L. Trevaskis; Jamie S. Simpson; Christopher J.H. Porter. 2020. "The Impact of Conjugation Position and Linker Chemistry on the Lymphatic Transport of a Series of Glyceride and Phospholipid Mimetic Prodrugs." Journal of Pharmaceutical Sciences 110, no. 1: 489-499.
The advent of immunotherapy has revolutionised the treatment of some cancers. Harnessing the immune system to improve tumour cell killing is now standard clinical practice and immunotherapy is the first line of defence for many cancers that historically, were difficult to treat. A unifying concept in cancer immunotherapy is the activation of the immune system to mount an attack on malignant cells, allowing the body to recognise, and in some cases, eliminate cancer. However, in spite of a significant proportion of patients that respond well to treatment, there remains a subset who are non-responders and a number of cancers that cannot be treated with these therapies. These limitations highlight the need for targeted delivery of immunomodulators to both tumours and the effector cells of the immune system, the latter being highly concentrated in the lymphatic system. In this context, macromolecular therapies may provide a significant advantage. Macromolecules are too large to easily access blood capillaries and instead typically exhibit preferential uptake via the lymphatic system. In contexts where immune cells are the therapeutic target, particularly in cancer therapy, this may be advantageous. In this review, we examine in brief the current immunotherapy approaches in cancer and how macromolecular and nanomedicine strategies may improve the therapeutic profiles of these drugs. We subsequently discuss how therapeutics directed either by parenteral or mucosal administration, can be taken up by the lymphatics thereby accessing a larger proportion of the body's immune cells. Finally, we detail drug delivery strategies that have been successfully employed to target the lymphatics.
Orlagh M. Feeney; Gracia Gracia; Daniel H.S. Brundel; Natalie L. Trevaskis; Enyuan Cao; Lisa M. Kaminskas; Christopher J.H. Porter. Lymph-directed immunotherapy – Harnessing endogenous lymphatic distribution pathways for enhanced therapeutic outcomes in cancer. Advanced Drug Delivery Reviews 2020, 160, 115 -135.
AMA StyleOrlagh M. Feeney, Gracia Gracia, Daniel H.S. Brundel, Natalie L. Trevaskis, Enyuan Cao, Lisa M. Kaminskas, Christopher J.H. Porter. Lymph-directed immunotherapy – Harnessing endogenous lymphatic distribution pathways for enhanced therapeutic outcomes in cancer. Advanced Drug Delivery Reviews. 2020; 160 ():115-135.
Chicago/Turabian StyleOrlagh M. Feeney; Gracia Gracia; Daniel H.S. Brundel; Natalie L. Trevaskis; Enyuan Cao; Lisa M. Kaminskas; Christopher J.H. Porter. 2020. "Lymph-directed immunotherapy – Harnessing endogenous lymphatic distribution pathways for enhanced therapeutic outcomes in cancer." Advanced Drug Delivery Reviews 160, no. : 115-135.
Editorial: Interplay of Infection and Microbiome
Wilhelmina M. Huston; Gilda Tachedjian. Editorial: Interplay of Infection and Microbiome. Frontiers in Cellular and Infection Microbiology 2020, 10, 304 .
AMA StyleWilhelmina M. Huston, Gilda Tachedjian. Editorial: Interplay of Infection and Microbiome. Frontiers in Cellular and Infection Microbiology. 2020; 10 ():304.
Chicago/Turabian StyleWilhelmina M. Huston; Gilda Tachedjian. 2020. "Editorial: Interplay of Infection and Microbiome." Frontiers in Cellular and Infection Microbiology 10, no. : 304.
The Australasian Virology Society (AVS) aims to promote, support and advocate for the discipline of virology in the Australasian region. The society was incorporated in 2011 after 10 years operating as the Australian Virology Group (AVG) founded in 2001, coinciding with the inaugural biennial scientific meeting. AVS conferences aim to provide a forum for the dissemination of all aspects of virology, foster collaboration, and encourage participation by students and post-doctoral researchers. The tenth Australasian Virology Society (AVS10) scientific meeting was held on 2–5 December 2019 in Queenstown, New Zealand. This report highlights the latest research presented at the meeting, which included cutting-edge virology presented by our international plenary speakers Ana Fernandez-Sesma and Benjamin tenOever, and keynote Richard Kuhn. AVS10 honoured female pioneers in Australian virology, Lorena Brown and Barbara Coulson. We report outcomes from the AVS10 career development session on “Successfully transitioning from post-doc to lab head”, winners of best presentation awards, and the AVS gender equity policy, initiated in 2013. Plans for the 2021 meeting are underway which will celebrate the 20th anniversary of AVS where it all began, in Fraser Island, Queensland, Australia.
Karla J. Helbig; Rowena A. Bull; Rebecca Ambrose; Michael R. Beard; Helen Blanchard; Till Böcking; Brendon Chua; Agathe M. G. Colmant; Keaton M. Crosse; Damian F. J. Purcell; Johanna Fraser; Joshua A. Hayward; Stuart T. Hamilton; Matloob Husain; Robin MacDiarmid; Jason M. MacKenzie; Gregory W. Moseley; Thi H. O. Nguyen; Miguel E. Quiñones-Mateu; Karl Robinson; Chaturaka Rodrigo; Julio Rodriguez-Andres; Penny A. Rudd; Anja Werno; Peter White; Paul Young; Peter Speck; Merilyn Hibma; Heidi E. Drummer; Gilda Tachedjian. Tenth Scientific Biennial Meeting of the Australasian Virology Society—AVS10 2019. Viruses 2020, 12, 621 .
AMA StyleKarla J. Helbig, Rowena A. Bull, Rebecca Ambrose, Michael R. Beard, Helen Blanchard, Till Böcking, Brendon Chua, Agathe M. G. Colmant, Keaton M. Crosse, Damian F. J. Purcell, Johanna Fraser, Joshua A. Hayward, Stuart T. Hamilton, Matloob Husain, Robin MacDiarmid, Jason M. MacKenzie, Gregory W. Moseley, Thi H. O. Nguyen, Miguel E. Quiñones-Mateu, Karl Robinson, Chaturaka Rodrigo, Julio Rodriguez-Andres, Penny A. Rudd, Anja Werno, Peter White, Paul Young, Peter Speck, Merilyn Hibma, Heidi E. Drummer, Gilda Tachedjian. Tenth Scientific Biennial Meeting of the Australasian Virology Society—AVS10 2019. Viruses. 2020; 12 (6):621.
Chicago/Turabian StyleKarla J. Helbig; Rowena A. Bull; Rebecca Ambrose; Michael R. Beard; Helen Blanchard; Till Böcking; Brendon Chua; Agathe M. G. Colmant; Keaton M. Crosse; Damian F. J. Purcell; Johanna Fraser; Joshua A. Hayward; Stuart T. Hamilton; Matloob Husain; Robin MacDiarmid; Jason M. MacKenzie; Gregory W. Moseley; Thi H. O. Nguyen; Miguel E. Quiñones-Mateu; Karl Robinson; Chaturaka Rodrigo; Julio Rodriguez-Andres; Penny A. Rudd; Anja Werno; Peter White; Paul Young; Peter Speck; Merilyn Hibma; Heidi E. Drummer; Gilda Tachedjian. 2020. "Tenth Scientific Biennial Meeting of the Australasian Virology Society—AVS10 2019." Viruses 12, no. 6: 621.
The intestinal lymphatic system transports fluid, immune cells, dietary lipids, and highly lipophilic drugs from the intestine to the systemic circulation. These transport functions are important to health and when dysregulated contribute to pathology. This has generated significant interest in approaches to deliver drugs to the lymphatics. Most of the current understanding of intestinal lymph flow, and lymphatic lipid and drug transport rates, comes from in vitro studies and in vivo animal studies. In contrast, intestinal lymphatic transport studies in human subjects have been limited. Recently, three surgical patients had cannulation of the thoracic lymph duct for collection of lymph before and during a stepwise increase in enteral feed rate. We compared these data to studies where we previously enterally administered controlled quantities of lipid and the lipophilic drug halofantrine to mice, rats and dogs and collected lymph and blood (plasma). The collected lymph was analyzed to compare lymph flow rate, triglyceride (TG) and drug transport rates, and plasma was analyzed for drug concentrations, as a function of enteral lipid dose across species. Lymph flow rate, TG and drug transport increased with lipid administration in all species tested, and scaled allometrically according to the equation A = aME where A is the lymph transport parameter, M is animal body mass, a is constant and E is the allometric exponent. For lymph flow rate and TG transport, the allometric exponents were 0.84–0.94 and 0.80–0.96, respectively. Accordingly, weight normalized lymph flow and TG mass transport were generally lower in larger compared to smaller species. In comparison, mass transport of drug via lymph increased in a greater than proportional manner with species body mass with an exponent of ∼1.3. The supra-proportional increase in lymphatic drug transport with species body mass appeared to be due to increased partitioning of drug into lymph rather than blood following absorption. Overall, this study proposes that intestinal lymphatic flow, and lymphatic lipid and drug transport in humans is most similar to species with higher body mass such as dogs and underestimated by studies in rodents. Notably, lymph flow and lipid transport in humans can be predicted from animal data via allometric scaling suggesting the potential for similar relationships with drug transport.
Natalie L. Trevaskis; Given Lee; Alistair Escott; Kian Liun Phang; Jiwon Hong; Enyuan Cao; Kasiram Katneni; Susan A. Charman; Sifei Han; William N. Charman; Anthony R. J. Phillips; John A. Windsor; Christopher J. H. Porter. Intestinal Lymph Flow, and Lipid and Drug Transport Scale Allometrically From Pre-clinical Species to Humans. Frontiers in Physiology 2020, 11, 458 .
AMA StyleNatalie L. Trevaskis, Given Lee, Alistair Escott, Kian Liun Phang, Jiwon Hong, Enyuan Cao, Kasiram Katneni, Susan A. Charman, Sifei Han, William N. Charman, Anthony R. J. Phillips, John A. Windsor, Christopher J. H. Porter. Intestinal Lymph Flow, and Lipid and Drug Transport Scale Allometrically From Pre-clinical Species to Humans. Frontiers in Physiology. 2020; 11 ():458.
Chicago/Turabian StyleNatalie L. Trevaskis; Given Lee; Alistair Escott; Kian Liun Phang; Jiwon Hong; Enyuan Cao; Kasiram Katneni; Susan A. Charman; Sifei Han; William N. Charman; Anthony R. J. Phillips; John A. Windsor; Christopher J. H. Porter. 2020. "Intestinal Lymph Flow, and Lipid and Drug Transport Scale Allometrically From Pre-clinical Species to Humans." Frontiers in Physiology 11, no. : 458.
Bats are reservoirs of emerging viruses that are highly pathogenic to other mammals, including humans. Despite the diversity and abundance of bat viruses, to date they have not been shown to harbor exogenous retroviruses. Here we report the discovery and characterization of a group of koala retrovirus-related (KoRV-related) gammaretroviruses in Australian and Asian bats. These include the Hervey pteropid gammaretrovirus (HPG), identified in the scat of the Australian black flying fox (Pteropus alecto), which is the first reproduction-competent retrovirus found in bats. HPG is a close relative of KoRV and the gibbon ape leukemia virus (GALV), with virion morphology and Mn2+-dependent virion-associated reverse transcriptase activity typical of a gammaretrovirus. In vitro, HPG is capable of infecting bat and human cells, but not mouse cells, and displays a similar pattern of cell tropism as KoRV-A and GALV. Population studies reveal the presence of HPG and KoRV-related sequences in several locations across northeast Australia, as well as serologic evidence for HPG in multiple pteropid bat species, while phylogenetic analysis places these bat viruses as the basal group within the KoRV-related retroviruses. Taken together, these results reveal bats to be important reservoirs of exogenous KoRV-related gammaretroviruses.
Joshua A. Hayward; Mary Tachedjian; Claudia Kohl; Adam Johnson; Megan Dearnley; Brianna Jesaveluk; Christine Langer; Philip D. Solymosi; Georg Hille; Andreas Nitsche; Cecilia A. Sánchez; Adam Werner; Dimitri Kontos; Gary Crameri; Glenn A. Marsh; Michelle L. Baker; Pantelis Poumbourios; Heidi E. Drummer; Edward C. Holmes; Lin-Fa Wang; Ina Smith; Gilda Tachedjian. Infectious KoRV-related retroviruses circulating in Australian bats. Proceedings of the National Academy of Sciences 2020, 117, 9529 -9536.
AMA StyleJoshua A. Hayward, Mary Tachedjian, Claudia Kohl, Adam Johnson, Megan Dearnley, Brianna Jesaveluk, Christine Langer, Philip D. Solymosi, Georg Hille, Andreas Nitsche, Cecilia A. Sánchez, Adam Werner, Dimitri Kontos, Gary Crameri, Glenn A. Marsh, Michelle L. Baker, Pantelis Poumbourios, Heidi E. Drummer, Edward C. Holmes, Lin-Fa Wang, Ina Smith, Gilda Tachedjian. Infectious KoRV-related retroviruses circulating in Australian bats. Proceedings of the National Academy of Sciences. 2020; 117 (17):9529-9536.
Chicago/Turabian StyleJoshua A. Hayward; Mary Tachedjian; Claudia Kohl; Adam Johnson; Megan Dearnley; Brianna Jesaveluk; Christine Langer; Philip D. Solymosi; Georg Hille; Andreas Nitsche; Cecilia A. Sánchez; Adam Werner; Dimitri Kontos; Gary Crameri; Glenn A. Marsh; Michelle L. Baker; Pantelis Poumbourios; Heidi E. Drummer; Edward C. Holmes; Lin-Fa Wang; Ina Smith; Gilda Tachedjian. 2020. "Infectious KoRV-related retroviruses circulating in Australian bats." Proceedings of the National Academy of Sciences 117, no. 17: 9529-9536.
Bats are recognised as important reservoirs of viruses deadly to other mammals, including humans. These infections are typically nonpathogenic in bats raising questions about host response differences that might exist between bats and other mammals. Tetherin is a restriction factor which inhibits the release of a diverse range of viruses from host cells, including retroviruses, coronaviruses, filoviruses, and paramyxoviruses, some of which are deadly to humans and transmitted by bats. Here we characterise the tetherin genes from 27 species of bats, revealing that they have evolved under strong selective pressure, and that fruit bats and vesper bats express unique structural variants of the tetherin protein. Tetherin was widely and variably expressed across fruit bat tissue-types and upregulated in spleen tissue when stimulated with Toll-like receptor agonists. The expression of two computationally predicted splice isoforms of fruit bat tetherin was verified. We identified an additional third unique splice isoform which includes a C-terminal region that is not homologous to known mammalian tetherin variants but was functionally capable of restricting the release of filoviral particles. We also report that vesper bats possess and express at least five tetherin genes, including structural variants, a greater number than any other mammal reported to date. These findings support the hypothesis of differential antiviral gene evolution in bats relative to other mammals.
Joshua Adam Hayward; Mary Tachedjian; Adam Johnson; Aaron T. Irving; Tamsin B. Gordon; Jie Cui; Alexis Nicolas; Ina Smith; Vicky Boyd; Glenn A. Marsh; Michelle L. Baker; Lin-Fa Wang; Gilda Tachedjian. Unique Evolution of Antiviral Tetherin in Bats. 2020, 1 .
AMA StyleJoshua Adam Hayward, Mary Tachedjian, Adam Johnson, Aaron T. Irving, Tamsin B. Gordon, Jie Cui, Alexis Nicolas, Ina Smith, Vicky Boyd, Glenn A. Marsh, Michelle L. Baker, Lin-Fa Wang, Gilda Tachedjian. Unique Evolution of Antiviral Tetherin in Bats. . 2020; ():1.
Chicago/Turabian StyleJoshua Adam Hayward; Mary Tachedjian; Adam Johnson; Aaron T. Irving; Tamsin B. Gordon; Jie Cui; Alexis Nicolas; Ina Smith; Vicky Boyd; Glenn A. Marsh; Michelle L. Baker; Lin-Fa Wang; Gilda Tachedjian. 2020. "Unique Evolution of Antiviral Tetherin in Bats." , no. : 1.
Structure/property relationship of API IL counterions and salt physicochemical properties are investigated, the results highlight the complex interplay involved.
Leigh Ford; Erin Tay; Tri-Hung Nguyen; Hywel D. Williams; Hassan Benameur; Peter J. Scammells; Christopher J. H. Porter. API ionic liquids: probing the effect of counterion structure on physical form and lipid solubility. RSC Advances 2020, 10, 12788 -12799.
AMA StyleLeigh Ford, Erin Tay, Tri-Hung Nguyen, Hywel D. Williams, Hassan Benameur, Peter J. Scammells, Christopher J. H. Porter. API ionic liquids: probing the effect of counterion structure on physical form and lipid solubility. RSC Advances. 2020; 10 (22):12788-12799.
Chicago/Turabian StyleLeigh Ford; Erin Tay; Tri-Hung Nguyen; Hywel D. Williams; Hassan Benameur; Peter J. Scammells; Christopher J. H. Porter. 2020. "API ionic liquids: probing the effect of counterion structure on physical form and lipid solubility." RSC Advances 10, no. 22: 12788-12799.
Non-optimal vaginal microbiota, as observed in bacterial vaginosis (BV), is typically characterized by a depletion of beneficial lactobacilli and an abundance of numerous anaerobes. These non-optimal conditions are associated with subclinical cervicovaginal inflammation and an increased risk of HIV infection compared to women colonized with optimal vaginal microbiota dominated by lactobacilli. Lactic acid (LA) is a major organic acid metabolite produced by vaginal lactobacilli that elicits anti-inflammatory effects from cervicovaginal epithelial cells and is dramatically depleted during BV. However, it is unclear if LA retains its anti-inflammatory activity in the presence of vaginal microbiota metabolites comprising short chain fatty acids (SCFAs) and succinic acid, which are also produced by an optimal vaginal microbiota. Furthermore, the immunomodulatory effect of SCFAs and succinic acid on cervicovaginal epithelial cells at higher concentrations present during BV is unknown. Here we report that in the presence of physiologically relevant concentrations of SCFAs and succinic acid at pH 3.9 (as found in women with lactobacillus-dominated microbiota) LA induced an anti-inflammatory state in cervicovaginal epithelial cells and inhibited inflammation elicited by the toll-like receptor (TLR) agonists polyinosinic:polycytidylic acid and Pam3CSK4. When cervicovaginal epithelial cells were treated with a vaginal microbiota metabolite mixture representative of BV, containing a lower concentration of LA but higher concentrations of SCFA/succinic acid at pH 7, no anti-inflammatory was observed. Rather, the vaginal microbiota metabolite mixture representative of BV dysregulated the immune response of cervicovaginal epithelial cells during prolonged and sustained treatments. This was evidenced by increased basal and TLR-induced production of pro-inflammatory cytokines including tumor necrosis factor-α, but decreased basal production of chemokines including RANTES and IP-10. Further characterization of individual components of the BV vaginal microbiota mixture suggested that acetic acid is an important vaginal microbiota metabolite capable of eliciting diverse immunomodulatory effects on a range of cervicovaginal epithelial cell targets. These findings indicate that elevated levels of SCFAs are a potential source of cervicovaginal inflammation in women experiencing BV, and support the unique anti-inflammatory properties of LA on cervicovaginal epithelial cells as well as a role for LA or LA-producing lactobacilli to reverse genital inflammation associated with increased HIV risk.
David J. Delgado-Diaz; David Tyssen; Joshua A. Hayward; Raffi Gugasyan; Anna C. Hearps; Gilda Tachedjian. Distinct Immune Responses Elicited From Cervicovaginal Epithelial Cells by Lactic Acid and Short Chain Fatty Acids Associated With Optimal and Non-optimal Vaginal Microbiota. Frontiers in Cellular and Infection Microbiology 2020, 9, 446 .
AMA StyleDavid J. Delgado-Diaz, David Tyssen, Joshua A. Hayward, Raffi Gugasyan, Anna C. Hearps, Gilda Tachedjian. Distinct Immune Responses Elicited From Cervicovaginal Epithelial Cells by Lactic Acid and Short Chain Fatty Acids Associated With Optimal and Non-optimal Vaginal Microbiota. Frontiers in Cellular and Infection Microbiology. 2020; 9 ():446.
Chicago/Turabian StyleDavid J. Delgado-Diaz; David Tyssen; Joshua A. Hayward; Raffi Gugasyan; Anna C. Hearps; Gilda Tachedjian. 2020. "Distinct Immune Responses Elicited From Cervicovaginal Epithelial Cells by Lactic Acid and Short Chain Fatty Acids Associated With Optimal and Non-optimal Vaginal Microbiota." Frontiers in Cellular and Infection Microbiology 9, no. : 446.
Background HIV and bacterial sexually transmissible infection (STI) notifications among men who have sex with men (MSM) have increased in Australia and many other countries. The relationship between HIV infection and other STIs has been demonstrated previously. However, the relationship between the cumulative history of STIs and subsequent HIV infection remains largely unexplored and limits our understanding of the mechanisms underpinning the elevated HIV risk. Methods Data from HIV-negative MSM who attended high–HIV caseload primary care clinics in Melbourne, Australia, from 2007 to 2014 with 2 or more HIV and STI tests were included. Controlling for sexual behaviors self-reported at clinic visits, discrete time survival analyses using generalized linear modeling estimated the effect of an STI at the prior test event and the cumulative history of STIs (none, 1, 2, or more [repeated]) on risk of HIV infection. Results A total of 8941 MSM met the study criteria; 227 (2.5%) were diagnosed with HIV over the follow-up period. Adjusting for sexual behaviors, a cumulative history of repeated rectal gonorrhea infections (adjusted hazard ratio [aHR], 6.27; 95% confidence interval [CI], 2.68–14.50) and a single rectal gonorrhea infection (aHR, 2.09; 95% CI, 1.15–3.79) were associated with increased HIV infection risk. Conclusions Repeated and single rectal gonorrhea infections were independently associated with increased HIV infection risk. These findings suggest that MSM with any history of rectal gonorrhea, particularly repeat rectal gonorrhea, represent a group for whom preventive interventions for HIV should be emphasized.
Brendan L Harney; Paul Agius; Carol El-Hayek; Christopher K Fairley; Eric Pui Fung Chow; Norman Roth; B K Tee; David Leslie; Gilda Tachedjian; Margaret Hellard; Mark Stoové. Risk of Subsequent HIV Infection Following Sexually Transmissible Infections Among Men Who Have Sex With Men. Open Forum Infectious Diseases 2019, 6, ofz376 .
AMA StyleBrendan L Harney, Paul Agius, Carol El-Hayek, Christopher K Fairley, Eric Pui Fung Chow, Norman Roth, B K Tee, David Leslie, Gilda Tachedjian, Margaret Hellard, Mark Stoové. Risk of Subsequent HIV Infection Following Sexually Transmissible Infections Among Men Who Have Sex With Men. Open Forum Infectious Diseases. 2019; 6 (10):ofz376.
Chicago/Turabian StyleBrendan L Harney; Paul Agius; Carol El-Hayek; Christopher K Fairley; Eric Pui Fung Chow; Norman Roth; B K Tee; David Leslie; Gilda Tachedjian; Margaret Hellard; Mark Stoové. 2019. "Risk of Subsequent HIV Infection Following Sexually Transmissible Infections Among Men Who Have Sex With Men." Open Forum Infectious Diseases 6, no. 10: ofz376.
Supraparticles (SPs) assembled from smaller colloidal nanoparticles can serve as depots of therapeutic compounds and are of interest for long-term, sustained drug release in biomedical applications. However, a key challenge to achieving temporal control of drug release from SPs is the occurrence of an initial rapid release of the loaded drug (i.e., "burst" release) that limits sustained release and potentially causes burst release-associated drug toxicity. Herein, a biocoating strategy is presented for silica-SPs (Si-SPs) to reduce the extent of burst release of the loaded model protein lysozyme. Specifically, Si-SPs were coated with a fibrin film, formed by enzymatic conversion of fibrinogen into fibrin. The fibrin-coated Si-SPs, FSi-SPs, which could be loaded with 7.9 ± 0.9 μg of lysozyme per SP, released >60% of cargo protein over a considerably longer period of time of >20 days when compared with the uncoated Si-SPs that released the same amount of the cargo protein, however, within the first 3 days. Neurotrophins that support the survival and differentiation of neurons could also be loaded at ∼7.3 μg per SP, with fibrin coating also delaying neurotrophin release (only 10% of cargo released over 21 days compared with 60% from Si-SPs). In addition, the effects of incorporating a hydrogel-based system for surgical delivery and the opportunity to control drug release kinetics were investigated-an alginate-based hydrogel scaffold was used to encapsulate FSi-SPs. The introduction of the hydrogel further extended the initial release of the encapsulated lysozyme to ∼40 days (for the same amount of cargo released). The results demonstrate the increasing versatility of the SP drug delivery platform, combining large loading capacity with sustained drug release, that is tailorable using different modes of controlled delivery approaches.
Yutian Ma; Christina Cortez-Jugo; Jianhua Li; Zhixing Lin; Rachael Richardson; Yiyuan Han; Jiajing Zhou; Mattias Björnmalm; Orlagh M. Feeney; Qi-Zhi Zhong; Christopher J. H. Porter; Andrew K. Wise; Frank Caruso. Engineering Biocoatings To Prolong Drug Release from Supraparticles. Biomacromolecules 2019, 20, 3425 -3434.
AMA StyleYutian Ma, Christina Cortez-Jugo, Jianhua Li, Zhixing Lin, Rachael Richardson, Yiyuan Han, Jiajing Zhou, Mattias Björnmalm, Orlagh M. Feeney, Qi-Zhi Zhong, Christopher J. H. Porter, Andrew K. Wise, Frank Caruso. Engineering Biocoatings To Prolong Drug Release from Supraparticles. Biomacromolecules. 2019; 20 (9):3425-3434.
Chicago/Turabian StyleYutian Ma; Christina Cortez-Jugo; Jianhua Li; Zhixing Lin; Rachael Richardson; Yiyuan Han; Jiajing Zhou; Mattias Björnmalm; Orlagh M. Feeney; Qi-Zhi Zhong; Christopher J. H. Porter; Andrew K. Wise; Frank Caruso. 2019. "Engineering Biocoatings To Prolong Drug Release from Supraparticles." Biomacromolecules 20, no. 9: 3425-3434.
Over-the-counter intra-vaginal lactic-acid containing douches are marketed as vaginal hygiene products that support optimal vaginal pH balance. We report the effect of a commercially available douche (Etos®) on the vaginal microbiota (VM) in a prospective study. Twenty-five healthy women were recruited through advertisements in 2015–2017 (ethical approval: METC-2014_413) and followed over three menstrual cycles. The participants had a median age of 24 years [IQR: 22–29], were mostly Dutch-Caucasian (88%), and 60% used combined oral contraceptives. All participants douched three times a week during the second cycle, starting on the first day of that cycle. Participants completed a questionnaire at baseline, kept a daily diary to report douching, menses, and sexual activity, self-collected vaginal swabs every other day during the first and third cycle and daily during the second cycle, and measured vaginal pH mid-cycle. A median of 44 vaginal swabs [inter-quartile range (IQR): 41–50] were assessed per participant by 16S rRNA gene (V3-V4 region) sequencing and a Candida albicans PCR was done at four time-points. At baseline, 21 participants (84%) had Lactobacillus-dominated VM (Lactobacillus crispatus (n = 14), L. iners (n = 6), or diverse Lactobacillus species (n = 1) and 4 participants (16%) had VM consisting of diverse anaerobes. In multinomial logistic regression models, a trend towards increased odds were observed for having diverse anaerobic VM in the second and third cycle, compared to the first cycle, after adjusting for menses [odds ratio (OR) = 1.4 (95% CI: 0.9–2.1) and OR = 1.7 (95% CI: 0.9–3.1), respectively] (p = 0.376). Douching did not affect vaginal pH. Menses increased the odds for having VM consisting of diverse anaerobes almost two-fold (OR = 1.7; 95% CI: 1.0–2.8), while douching during menses increased the odds 2.6 fold (OR = 2.6; 95% CI: 1.0–6.5), compared to not menstruating (p = 0.099). Participants were more likely to test positive for C. albicans after cycle 2, compared to cycle 1 [OR = 3.0 (95% CI: 1.2–7.2); p = 0.017]. The Etos® douche did not significantly affect the vaginal pH or VM composition, although increased odds for having diverse anaerobic VM was observed, especially when douching during menses. Furthermore, douching may promote C. albicans infections.
C. Van Der Veer; S. M. Bruisten; R. Van Houdt; A. A. Matser; G. Tachedjian; J. H. H. M. Van De Wijgert; H. J. C. De Vries; J. J. Van Der Helm. Effects of an over-the-counter lactic-acid containing intra-vaginal douching product on the vaginal microbiota. BMC Microbiology 2019, 19, 1 -13.
AMA StyleC. Van Der Veer, S. M. Bruisten, R. Van Houdt, A. A. Matser, G. Tachedjian, J. H. H. M. Van De Wijgert, H. J. C. De Vries, J. J. Van Der Helm. Effects of an over-the-counter lactic-acid containing intra-vaginal douching product on the vaginal microbiota. BMC Microbiology. 2019; 19 (1):1-13.
Chicago/Turabian StyleC. Van Der Veer; S. M. Bruisten; R. Van Houdt; A. A. Matser; G. Tachedjian; J. H. H. M. Van De Wijgert; H. J. C. De Vries; J. J. Van Der Helm. 2019. "Effects of an over-the-counter lactic-acid containing intra-vaginal douching product on the vaginal microbiota." BMC Microbiology 19, no. 1: 1-13.