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The current study introduces two novel, smart polymer three-dimensional (3D)-printable interpenetrating polymer network (IPN) hydrogel biomaterials with favorable chemical, mechanical, and morphological properties for potential applications in traumatic brain injury (TBI) such as potentially assisting in the restoration of neurological function through closure of the wound deficit and neural tissue regeneration. Additionally, removal of injury matter to allow for the appropriate scaffold grafting may assist in providing a TBI treatment. Furthermore, due to the 3D printability of the IPN biomaterials, complex structures can be designed and fabricated to mimic the native shape and structure of the injury sight, which can potentially assist with neural tissue regeneration after TBI. In this study, a peptide-only approach was employed, wherein collagen and elastin in a blend with gelatin methacryloyl were prepared and crosslinked using either Irgacure or Irgacure and Genipin to form either a semi or full IPN hydrogel 3D-printable neuromimicking platform system, respectively. The scaffolds displayed favorable thermal stability and were amorphous in nature with high full width at half-maximum values. Furthermore, no alteration to the peptide secondary structure was noted using Fourier transform infrared spectroscopy. The IPN biomaterials have a stiffness of around 600 Pa and are suitable for softer tissue engineering applications—that is, the brain. Scanning electron micrographs indicated that the IPN biomaterials had a morphological structure with a significant resemblance to the native rat cortex. Both biomaterial scaffolds were shown to support the growth of PC12 cells over a 72 h period. Furthermore, the increased nuclear eccentricity and nuclear area were shown to support the postulation that the IPN biomaterials maintain the cells in a healthy state encouraging cellular mitosis and proliferation. The Genipin component of the full IPN was further shown to exhibit antimicrobial properties and this suggests that Genipin can prevent the growth of pathogens associated with postsurgical brain infections. In addition to these findings, the study presents an anomaly, wherein the full IPN is found to be more brittle than the semi IPN, a finding that is in contradiction with the literature. This research, therefore, contributes to the collection of potential biomaterials for TBI applications coupled with 3D printing and can assist in the progression of neural treatments toward patient-specific scaffolds through the development of custom scaffolds.
Kate Da Silva; Pradeep Kumar; Sandy F. van Vuuren; Viness Pillay; Yahya E. Choonara. Three-Dimensional Printability of an ECM-Based Gelatin Methacryloyl (GelMA) Biomaterial for Potential Neuroregeneration. ACS Omega 2021, 6, 21368 -21383.
AMA StyleKate Da Silva, Pradeep Kumar, Sandy F. van Vuuren, Viness Pillay, Yahya E. Choonara. Three-Dimensional Printability of an ECM-Based Gelatin Methacryloyl (GelMA) Biomaterial for Potential Neuroregeneration. ACS Omega. 2021; 6 (33):21368-21383.
Chicago/Turabian StyleKate Da Silva; Pradeep Kumar; Sandy F. van Vuuren; Viness Pillay; Yahya E. Choonara. 2021. "Three-Dimensional Printability of an ECM-Based Gelatin Methacryloyl (GelMA) Biomaterial for Potential Neuroregeneration." ACS Omega 6, no. 33: 21368-21383.
The development of nanoparticulate systems has been shown to be highly effective in the advancement of pharmaceutical drug delivery technology. The use of these systems, however, has been shown to have significant physical and chemical effects on blood constituents, especially when delivered via intravenous injection. These effects have been shown to impact not only the individual blood constituents and their physiological roles but also the efficacy of the nanoparticulate formulation as well. Numerous studies have therefore focused on the impacts of nanoparticulate delivery on blood and have detailed the modifications undertaken to ensure hemocompatibility. This chapter will therefore focus on the interactions between nanoparticulate delivery systems and blood constituents upon delivery, the effect of these interactions and the newer research that has been performed to overcome the known issues of nanoparticle blood compatibility.
Mershen Govender; Sunaina Indermun; Pradeep Kumar; Yahya E. Choonara; Viness Pillay. Injectable Nanosystems and Inherent Nanoparticulate-Serum Interactions. Emerging Technologies for Nanoparticle Manufacturing 2021, 561 -572.
AMA StyleMershen Govender, Sunaina Indermun, Pradeep Kumar, Yahya E. Choonara, Viness Pillay. Injectable Nanosystems and Inherent Nanoparticulate-Serum Interactions. Emerging Technologies for Nanoparticle Manufacturing. 2021; ():561-572.
Chicago/Turabian StyleMershen Govender; Sunaina Indermun; Pradeep Kumar; Yahya E. Choonara; Viness Pillay. 2021. "Injectable Nanosystems and Inherent Nanoparticulate-Serum Interactions." Emerging Technologies for Nanoparticle Manufacturing , no. : 561-572.
: Among all the anti-schistosomal drug, praziquantel has been the most widely used. However, some major challenges have been faced using the drug in the treatment of schistosome infections. : Several approaches used in the synthesis of praziquantel aimed at reducing the time and cost of production, the toxicity and experimental harsh conditions are discussed. Also, patented methods involved in the pharmaceutical reformulation of praziquantel in the treatment of diverse endoparasitic infestation are reported. Additionally, future perspectives in terms of nanomedicine approach in the formulation of praziquantel are highlighted. : Lipid-based nanosystems (LBNSs) formulations can be used to overcome the shortcomings associated with the used of praziquantel in the schistosomiasis treatment due to their amphiphatic nature. This could be a promising vehicle for the delivery of praziquantel, which could in turn improve the bioavailability, as well as reduce the frequent dose of the drug and improve patient compliance. This may sustain release of the drug and improve the rapid conversion of the drug into inactive metabolite due to rapid metabolism. Additionally, LBNSs approach could increase and improve the lipophilicity of the drug, which could make it easier to interact with the hydrophobic cores of the worm tegument.
Tayo A. Adekiya; Pradeep Kumar; Pierre P.D. Kondiah; Viness Pillay; Yahya E. Choonara. Synthesis and therapeutic delivery approaches for praziquantel: a patent review (2010-present). Expert Opinion on Therapeutic Patents 2021, 1 -15.
AMA StyleTayo A. Adekiya, Pradeep Kumar, Pierre P.D. Kondiah, Viness Pillay, Yahya E. Choonara. Synthesis and therapeutic delivery approaches for praziquantel: a patent review (2010-present). Expert Opinion on Therapeutic Patents. 2021; ():1-15.
Chicago/Turabian StyleTayo A. Adekiya; Pradeep Kumar; Pierre P.D. Kondiah; Viness Pillay; Yahya E. Choonara. 2021. "Synthesis and therapeutic delivery approaches for praziquantel: a patent review (2010-present)." Expert Opinion on Therapeutic Patents , no. : 1-15.
This investigation focused on the design of an injectable nano-enabled thermogel (nano-thermogel) system to attain controlled delivery of p11 anti-angiogenic peptide for proposed effective prevention of neovascularisation and to overcome the drawbacks of the existing treatment approaches for ocular disorders characterised by angiogenesis, which employ multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) antibodies. Synthesis of a polyethylene glycol-polycaprolactone-polyethylene glycol (PEG-PCL-PEG) triblock co-polymer was undertaken, followed by characterisation employing Fourier-transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy and differential scanning calorimetry (DSC) to ascertain the chemical stability and integrity of the co-polymer instituted for nano-thermogel formulation. The p11 anti-angiogenic peptide underwent encapsulation within poly(lactic-co-glycolic acid) (PLGA) nanoparticles via a double emulsion solvent evaporation method and was incorporated into the thermogel following characterisation by scanning electron microscopy (SEM), zeta size and zeta-potential analysis. The tube inversion approach and rheological analysis were employed to ascertain the thermo-sensitive sol-gel conversion of the nano-thermogel system. Chromatographic assessment of the in vitro release of the peptide was performed, with stability confirmation via Tris-Tricine PAGE (Polyacrylamide Gel Electrophoresis). In vitro biocompatibility of the nano-thermogel system was investigated employing a retinal cell line (ARP-19). A nanoparticle size range of 100–200 nm and peptide loading efficiency of 67% was achieved. Sol-gel conversion of the nano-thermogel was observed between 32–45 °C. Release of the peptide in vitro was sustained, with maintenance of stability, for 60 days. Biocompatibility assessment highlighted 97–99% cell viability with non-haemolytic ability, which supports the potential applicability of the nano-thermogel system for extended delivery of peptide for ocular disorder treatment.
Lisa Toit; Yahya Choonara; Viness Pillay. An Injectable Nano-Enabled Thermogel to Attain Controlled Delivery of p11 Peptide for the Potential Treatment of Ocular Angiogenic Disorders of the Posterior Segment. Pharmaceutics 2021, 13, 176 .
AMA StyleLisa Toit, Yahya Choonara, Viness Pillay. An Injectable Nano-Enabled Thermogel to Attain Controlled Delivery of p11 Peptide for the Potential Treatment of Ocular Angiogenic Disorders of the Posterior Segment. Pharmaceutics. 2021; 13 (2):176.
Chicago/Turabian StyleLisa Toit; Yahya Choonara; Viness Pillay. 2021. "An Injectable Nano-Enabled Thermogel to Attain Controlled Delivery of p11 Peptide for the Potential Treatment of Ocular Angiogenic Disorders of the Posterior Segment." Pharmaceutics 13, no. 2: 176.
Aim: In this study, curcumin was encapsulated in niosomes (Nio-Curc) to increase its effectiveness for the treatment of asthma. Materials & methods: The formulation underwent various physicochemical characterization experiments, an in vitro release study, molecular simulations and was evaluated for in vitro anti-inflammatory activity. Results: Results showed that Nio-Curc had a mean particle size of 284.93 ± 14.27 nm, zeta potential of -46.93 and encapsulation efficacy of 99.62%, which demonstrates optimized physicochemical characteristics. Curcumin release in vitro could be sustained for up to 24 h. Additionally, Nio-Curc effectively reduced mRNA transcript expression of pro-inflammatory markers; IL-6, IL-8, IL-1β and TNF-α in immortalized human airway basal cell line (BCi-NS1.1). Conclusion: In this study, we have demonstrated that Nio-Curc mitigated the mRNA expression of pro-inflammatory markers in an in vitro study, which could be applied to treatment of asthma with further studies.
Jin-Ying Wong; Zhao Yin Ng; Meenu Mehta; Shakti D Shukla; Jithendra Panneerselvam; Thiagarajan Madheswaran; Gaurav Gupta; Poonam Negi; Pradeep Kumar; Viness Pillay; Alan Hsu; Nicole G Hansbro; Peter Wark; Mary Bebawy; Philip Michael Hansbro; Kamal Dua; Dinesh Kumar Chellappan. Curcumin-loaded niosomes downregulate mRNA expression of pro-inflammatory markers involved in asthma: an in vitro study. Nanomedicine 2020, 15, 2955 -2970.
AMA StyleJin-Ying Wong, Zhao Yin Ng, Meenu Mehta, Shakti D Shukla, Jithendra Panneerselvam, Thiagarajan Madheswaran, Gaurav Gupta, Poonam Negi, Pradeep Kumar, Viness Pillay, Alan Hsu, Nicole G Hansbro, Peter Wark, Mary Bebawy, Philip Michael Hansbro, Kamal Dua, Dinesh Kumar Chellappan. Curcumin-loaded niosomes downregulate mRNA expression of pro-inflammatory markers involved in asthma: an in vitro study. Nanomedicine. 2020; 15 (30):2955-2970.
Chicago/Turabian StyleJin-Ying Wong; Zhao Yin Ng; Meenu Mehta; Shakti D Shukla; Jithendra Panneerselvam; Thiagarajan Madheswaran; Gaurav Gupta; Poonam Negi; Pradeep Kumar; Viness Pillay; Alan Hsu; Nicole G Hansbro; Peter Wark; Mary Bebawy; Philip Michael Hansbro; Kamal Dua; Dinesh Kumar Chellappan. 2020. "Curcumin-loaded niosomes downregulate mRNA expression of pro-inflammatory markers involved in asthma: an in vitro study." Nanomedicine 15, no. 30: 2955-2970.
In the last chapter, Das and Das have presented the advantages of biodegradable polymeric nanoparticles in biomedical use, and have also provided an overview of general methods of fabricating and designing nanoparticles. In this chapter, we will continue to talk about nanoparticles as carriers of therapeutics, but will narrow down the focus of the discussions to the context of neurological aging. In fact, neurological disorders such as Parkinson’s disease, Alzheimer’s diseases, neuropathic pain, and cerebrovascular accidents affect approximately 1.5 billion people globally. Over the years, an array of bioactive molecules have been found to be effective for the treatment of neurological conditions but not to be clinically effective due to the presence of the blood–brain barrier (BBB). The BBB is primarily responsible for the separation of extracellular fluid and blood within the CNS, generating a selectively permeable barrier restricting the passage of an array of substances, such as drugs, biomolecules, and potentially pathogenic substances. Nanomedicine is an attractive non-invasive technology that can be employed to circumvent this barrier. In this chapter, we will review the current advancements and limitations for the employment of nanomedicine to treat neurological diseases, and will also delineate the clinical and regulatory requirement for market entry of these products.
Previn Ramiah; Pierre P. D. Kondiah; Yahya E. Choonara; Lisa C. Du Toit; Viness Pillay. Use of Nanoparticulate Systems for Tackling Neurological Aging. Healthy Ageing and Longevity 2020, 187 -218.
AMA StylePrevin Ramiah, Pierre P. D. Kondiah, Yahya E. Choonara, Lisa C. Du Toit, Viness Pillay. Use of Nanoparticulate Systems for Tackling Neurological Aging. Healthy Ageing and Longevity. 2020; ():187-218.
Chicago/Turabian StylePrevin Ramiah; Pierre P. D. Kondiah; Yahya E. Choonara; Lisa C. Du Toit; Viness Pillay. 2020. "Use of Nanoparticulate Systems for Tackling Neurological Aging." Healthy Ageing and Longevity , no. : 187-218.
Traumatic brain injury (TBI) presents a serious challenge for modern medicine due to the poor regenerative capabilities of the brain, complex pathophysiology, and lack of effective treatment for TBI to date. Tissue-engineered scaffolds have shown some experimental success in vivo; unfortunately, none have yielded consummate results of clinical efficacy. N-acetylcysteine has shown neuroprotective potential. To this end, we developed a N-acetylcysteine (NAC)-loaded poly(lactic-co-glycolic acid) (PLGA) electrospun system for potential neural tissue application for TBI. Scanning electron microscopy showed nanofiber diameters ranging 72–542 nm and 124–592 nm for NAC-free and NAC-loaded PLGA nanofibers, respectively. NAC loading was obtained at 28%, and drug entrapment efficacy was obtained at 84%. A biphasic NAC release pattern that featured an initial burst release (13.9%) stage and a later sustained release stage was noted, thus enabling the prolonged replenishing of NAC and drastically improving cell viability and proliferation. This was evidenced by a significantly higher cell viability and proliferation on NAC-loaded nanofibers for rat pheochromocytoma (PC12) and human glioblastoma multiform (A172) cell lines in comparison to PLGA-only nanofibers. The increased cell viability and cell proliferation on NAC-loaded nanofiber substantiates for the repositioning of NAC as a pharmacological agent in neural tissue regeneration applications.
Gillian Mahumane; Pradeep Kumar; Viness Pillay; Yahya Choonara. Repositioning N-Acetylcysteine (NAC): NAC-Loaded Electrospun Drug Delivery Scaffolding for Potential Neural Tissue Engineering Application. Pharmaceutics 2020, 12, 934 .
AMA StyleGillian Mahumane, Pradeep Kumar, Viness Pillay, Yahya Choonara. Repositioning N-Acetylcysteine (NAC): NAC-Loaded Electrospun Drug Delivery Scaffolding for Potential Neural Tissue Engineering Application. Pharmaceutics. 2020; 12 (10):934.
Chicago/Turabian StyleGillian Mahumane; Pradeep Kumar; Viness Pillay; Yahya Choonara. 2020. "Repositioning N-Acetylcysteine (NAC): NAC-Loaded Electrospun Drug Delivery Scaffolding for Potential Neural Tissue Engineering Application." Pharmaceutics 12, no. 10: 934.
Synthesis of a novel theranostic molecule for targeted cancer intervention. A reaction between curcumin and lawsone was carried out to yield the novel curcumin naphthoquinone (CurNQ) molecule (2,2′-((((1E,3Z,6E)-3-hydroxy-5-oxohepta-1,3,6-triene-1,7-diyl) bis(2-methoxy-4,1-phenylene))bis(oxy))bis(naphthalene-1,4-dione). CurNQ’s structure was elucidated and was fully characterized. CurNQ was demonstrated to have pH specific solubility, its saturation solubility increased from 11.15 µM at pH 7.4 to 20.7 µM at pH 6.8. This pH responsivity allows for cancer targeting (Warburg effect). Moreover, CurNQ displayed intrinsic fluorescence, thus enabling imaging and detection applications. In vitro cytotoxicity assays demonstrated the chemotherapeutic properties of CurNQ as CurNQ reduced cell viability to below 50% in OVCAR-5 and SKOV3 ovarian cancer cell lines. CurNQ is a novel theranostic molecule for potential targeted cancer detection and treatment.
Lara Freidus; Pradeep Kumar; Thashree Marimuthu; Priyamvada Pradeep; Viness Pillay; Yahya Choonara. Synthesis and Properties of CurNQ for the Theranostic Application in Ovarian Cancer Intervention. Molecules 2020, 25, 4471 .
AMA StyleLara Freidus, Pradeep Kumar, Thashree Marimuthu, Priyamvada Pradeep, Viness Pillay, Yahya Choonara. Synthesis and Properties of CurNQ for the Theranostic Application in Ovarian Cancer Intervention. Molecules. 2020; 25 (19):4471.
Chicago/Turabian StyleLara Freidus; Pradeep Kumar; Thashree Marimuthu; Priyamvada Pradeep; Viness Pillay; Yahya Choonara. 2020. "Synthesis and Properties of CurNQ for the Theranostic Application in Ovarian Cancer Intervention." Molecules 25, no. 19: 4471.
Poor circulation stability and inadequate cell membrane penetration are significant impediments in the implementation of nanocarriers as delivery systems for therapeutic agents with low bioavailability. This research discusses the fabrication of a biocompatible poly(lactide-co-glycolide) (PLGA) based nanocarrier with cationic and hydrophilic surface properties provided by natural polymer chitosan and coating polymer polyethylene glycol (PEG) for the entrapment of the hydrophobic drug disulfiram. The traditional emulsification solvent evaporation method was compared to a microfluidics-based method of fabrication, with the optimisation of the parameters for each method, and the PEGylation densities on the experimental nanoparticle formulations were varied. The size and surface properties of the intermediates and products were characterised and compared by dynamic light scattering, scanning electron microscopy and X-ray diffraction, while the thermal properties were investigated using thermogravimetric analysis and differential scanning calorimetry. Results showed optimal particle properties with an intermediate PEG density and a positive surface charge for greater biocompatibility, with nanoparticle surface characteristics shielding physical interaction of the entrapped drug with the exterior. The formulations prepared using the microfluidic method displayed superior surface charge, entrapment and drug release properties. The final system shows potential as a component of a biocompatible nanocarrier for poorly soluble drugs.
Divesha Essa; Yahya E. Choonara; Pierre P. D. Kondiah; Viness Pillay. Comparative Nanofabrication of PLGA-Chitosan-PEG Systems Employing Microfluidics and Emulsification Solvent Evaporation Techniques. Polymers 2020, 12, 1882 .
AMA StyleDivesha Essa, Yahya E. Choonara, Pierre P. D. Kondiah, Viness Pillay. Comparative Nanofabrication of PLGA-Chitosan-PEG Systems Employing Microfluidics and Emulsification Solvent Evaporation Techniques. Polymers. 2020; 12 (9):1882.
Chicago/Turabian StyleDivesha Essa; Yahya E. Choonara; Pierre P. D. Kondiah; Viness Pillay. 2020. "Comparative Nanofabrication of PLGA-Chitosan-PEG Systems Employing Microfluidics and Emulsification Solvent Evaporation Techniques." Polymers 12, no. 9: 1882.
Three Dimensional Printing (3DP) technology has evolved as an emerging technique with huge potential having a promising impact on the production of pharmaceuticals using simple and rapid strategies for product fabrication. The applications of 3DP have found an amazing and incredible approach in drug delivery field including space pharmaceuticals. The increasing human explorations to space demand an overview of the available medications that could help in the maintenance of wellness of astronauts and their performance during long space travel to weightlessness since there exists a huge difference between the microgravity and terrestrial environments. The absorption, distribution, metabolism, and excretion of active agents might be different in space owing to the physiological alterations that occur during spaceflights viz-a-viz muscle loss and cardiovascular changes, fluid loss, and fluid shifts. In addition to the potential implications of the microgravity on drug therapeutic effect and safety due to the changes in pharmacokinetic and/or pharmacodynamic profiles of medication, changes in stability of drug in weightlessness could also affect drug efficiency during spaceflights. Based on these knowledge gaps, studies that seek to understand drug effects in space should be given preference, for example, based on their usage. Such investigations are likely to depend more on newer, less-invasive techniques such as 3DP strategies, unmanned space vehicles due to automatization, which decreases astronauts’ workload. In this regard, customized dosage forms can be fabricated in-flight with multi-faceted drug release kinetics for precision and personalized therapy. In-depth understanding of space pharmacology can assist in the choice of space pharmaceuticals with predictable therapeutic responses in prolonged missions such as the expected alterations of their receptor binding, or major route of elimination, flexible dosage, and ultimately effective and enhanced treatment outcomes.
Viness Pillay; Samson A. Adeyemi; Pradeep Kumar; Lisa C. Du Toit; Yahya E. Choonara. Three Dimensional Printing (3DP) for Space Pharmaceuticals. Handbook of Space Pharmaceuticals 2020, 1 -38.
AMA StyleViness Pillay, Samson A. Adeyemi, Pradeep Kumar, Lisa C. Du Toit, Yahya E. Choonara. Three Dimensional Printing (3DP) for Space Pharmaceuticals. Handbook of Space Pharmaceuticals. 2020; ():1-38.
Chicago/Turabian StyleViness Pillay; Samson A. Adeyemi; Pradeep Kumar; Lisa C. Du Toit; Yahya E. Choonara. 2020. "Three Dimensional Printing (3DP) for Space Pharmaceuticals." Handbook of Space Pharmaceuticals , no. : 1-38.
Background/issues: Nanomaterials have been effectively and widely utilized in a variety of scientific disciplines to enhance biomedical applications. These nanomaterials are often organic or inorganic and often comprised of polymers or metal derivatives. The therapeutic safety of these often-toxic materials, however, is of paramount importance to ensure therapeutic safety. The safety of nanomaterials is therefore a widely undertaken research discipline evaluated both in vitro and in vivo. Major advances: This review provides for the currently undertaken research for the determination of therapeutic safety in inorganic nanomaterials. The importance of therapeutic safety, toxicity, and regulation of nanomaterials has been provided prior to the review of the respective nanomaterials. Specific focus has been given to metal-derived nanomaterials including gold, silver, silica, copper, iron, zinc, and titanium nanomaterials. Toxicology profiling and cytotoxicity studies of these nanomaterials have also been provided in addition to the in vivo studies that have been undertaken and the potential for alternative nanomaterial safety assessments.
Sunaina Indermun; Mershen Govender; Pradeep Kumar; Yahya E. Choonara; Viness Pillay. Inorganic Nanomaterials for Enhanced Therapeutic Safety. Nanosensors for Environment, Food and Agriculture Vol. 1 2020, 1 -24.
AMA StyleSunaina Indermun, Mershen Govender, Pradeep Kumar, Yahya E. Choonara, Viness Pillay. Inorganic Nanomaterials for Enhanced Therapeutic Safety. Nanosensors for Environment, Food and Agriculture Vol. 1. 2020; ():1-24.
Chicago/Turabian StyleSunaina Indermun; Mershen Govender; Pradeep Kumar; Yahya E. Choonara; Viness Pillay. 2020. "Inorganic Nanomaterials for Enhanced Therapeutic Safety." Nanosensors for Environment, Food and Agriculture Vol. 1 , no. : 1-24.
Tankyrase enzymes (TNKS), a core part of the canonical Wnt pathway, are a promising target in the search for potential anti-cancer agents. Although several hundreds of the TNKS inhibitors are currently known, identification of their novel chemotypes attracts considerable interest. In this study, the molecular docking and machine learning-based virtual screening techniques combined with the physico-chemical and ADMET (absorption, distribution, metabolism, excretion, toxicity) profile prediction and molecular dynamics simulations were applied to a subset of the ZINC database containing about 1.7 M commercially available compounds. Out of seven candidate compounds biologically evaluated in vitro for their inhibition of the TNKS2 enzyme using immunochemical assay, two compounds have shown a decent level of inhibitory activity with the IC50 values of less than 10 nM and 10 μM. Relatively simple scores based on molecular docking or MM-PBSA (molecular mechanics, Poisson-Boltzmann, surface area) methods proved unsuitable for predicting the effect of structural modification or for accurate ranking of the compounds based on their binding energies. On the other hand, the molecular dynamics simulations and Free Energy Perturbation (FEP) calculations allowed us to further decipher the structure-activity relationships and retrospectively analyze the docking-based virtual screening performance. This approach can be applied at the subsequent lead optimization stages.
Vladimir Berishvili; Alexander Kuimov; Andrew Voronkov; Eugene Radchenko; Pradeep Kumar; Yahya Choonara; Viness Pillay; Ahmed Kamal; Vladimir Palyulin. Discovery of Novel Tankyrase Inhibitors through Molecular Docking-Based Virtual Screening and Molecular Dynamics Simulation Studies. Molecules 2020, 25, 3171 .
AMA StyleVladimir Berishvili, Alexander Kuimov, Andrew Voronkov, Eugene Radchenko, Pradeep Kumar, Yahya Choonara, Viness Pillay, Ahmed Kamal, Vladimir Palyulin. Discovery of Novel Tankyrase Inhibitors through Molecular Docking-Based Virtual Screening and Molecular Dynamics Simulation Studies. Molecules. 2020; 25 (14):3171.
Chicago/Turabian StyleVladimir Berishvili; Alexander Kuimov; Andrew Voronkov; Eugene Radchenko; Pradeep Kumar; Yahya Choonara; Viness Pillay; Ahmed Kamal; Vladimir Palyulin. 2020. "Discovery of Novel Tankyrase Inhibitors through Molecular Docking-Based Virtual Screening and Molecular Dynamics Simulation Studies." Molecules 25, no. 14: 3171.
The present study aimed to formulate celastrol into liquid crystalline nanoparticles (LCNPs) through ultrasonication to enhance its therapeutic efficacy in the treatment of asthma. The physiochemical characteristics, in-vitro release studies were determined along with molecular simulations. Celastrol-loaded LCNPs showed the mean particle size of 194.1 ± 9.78 nm and high entrapment efficiency of 99.1 ± 0.02%. TEM revealed cubical-like structure of the nanoparticles and in-vitro release study demonstrated sustained drug release. They also demonstrated significant activity in reducing IL-1β production, when evaluated using immortalized human bronchial epithelial cell lines (BCi-NS1.1), that may help alleviate the symptoms of asthma.
Yinghan Chan; Sin Wi Ng; Dinesh Kumar Chellappan; Thiagarajan Madheswaran; Farrukh Zeeshan; Pradeep Kumar; Viness Pillay; Gaurav Gupta; Ridhima Wadhwa; Meenu Mehta; Peter Wark; Alan Hsu; Nicole G Hansbro; Philip Michael Hansbro; Kamal Dua; Jithendra Panneerselvam. Celastrol-loaded liquid crystalline nanoparticles as an anti-inflammatory intervention for the treatment of asthma. International Journal of Polymeric Materials and Polymeric Biomaterials 2020, 70, 754 -763.
AMA StyleYinghan Chan, Sin Wi Ng, Dinesh Kumar Chellappan, Thiagarajan Madheswaran, Farrukh Zeeshan, Pradeep Kumar, Viness Pillay, Gaurav Gupta, Ridhima Wadhwa, Meenu Mehta, Peter Wark, Alan Hsu, Nicole G Hansbro, Philip Michael Hansbro, Kamal Dua, Jithendra Panneerselvam. Celastrol-loaded liquid crystalline nanoparticles as an anti-inflammatory intervention for the treatment of asthma. International Journal of Polymeric Materials and Polymeric Biomaterials. 2020; 70 (11):754-763.
Chicago/Turabian StyleYinghan Chan; Sin Wi Ng; Dinesh Kumar Chellappan; Thiagarajan Madheswaran; Farrukh Zeeshan; Pradeep Kumar; Viness Pillay; Gaurav Gupta; Ridhima Wadhwa; Meenu Mehta; Peter Wark; Alan Hsu; Nicole G Hansbro; Philip Michael Hansbro; Kamal Dua; Jithendra Panneerselvam. 2020. "Celastrol-loaded liquid crystalline nanoparticles as an anti-inflammatory intervention for the treatment of asthma." International Journal of Polymeric Materials and Polymeric Biomaterials 70, no. 11: 754-763.
The loss of tissues and organs through injury and disease has stimulated the development of therapeutics that have the potential to regenerate and replace the affected tissue. Such therapeutics have the benefit of reducing the reliance and demand for life‐saving organ transplants. Of the several regenerative strategies, 3D printing has emerged as the forerunner in regenerative attempts due to the fact that biologically and anatomically correct 3D structures can be fabricated according to the specified need. Despite the progress in this field, improvement is still limited by the difficulty in fabricating scaffolds that adequately mimic the native cellular microenvironment. In response, despite the complexities of the native extracellular matrix (ECM), the inclusion of ECM components into bioinks has emerged as a cutting‐edge research area in terms of providing possible ECM‐mimicking abilities of the 3D printed constructs. Furthermore, the development of ECM‐mimicking scaffolds can potentially assist in improving personalised patient treatments. This review provides a critical analysis of selected naturally occurring ECM components as well as synthetic self‐assembling peptides in their ability to provide the required ECM microenvironment for tissue regeneration. The success and possible short comings of each material, as well as the specific characteristics of each bioink, is evaluated. This article is protected by copyright. All rights reserved.
Kate Da Silva; Pradeep Kumar; Yahya E. Choonara; Lisa C. Du Toit; Viness Pillay. Three‐dimensional printing of extracellular matrix ( ECM )‐mimicking scaffolds: A critical review of the current ECM materials. Journal of Biomedical Materials Research Part A 2020, 108, 2324 -2350.
AMA StyleKate Da Silva, Pradeep Kumar, Yahya E. Choonara, Lisa C. Du Toit, Viness Pillay. Three‐dimensional printing of extracellular matrix ( ECM )‐mimicking scaffolds: A critical review of the current ECM materials. Journal of Biomedical Materials Research Part A. 2020; 108 (12):2324-2350.
Chicago/Turabian StyleKate Da Silva; Pradeep Kumar; Yahya E. Choonara; Lisa C. Du Toit; Viness Pillay. 2020. "Three‐dimensional printing of extracellular matrix ( ECM )‐mimicking scaffolds: A critical review of the current ECM materials." Journal of Biomedical Materials Research Part A 108, no. 12: 2324-2350.
Three-dimensional (3D) printing of biomaterials provides an interesting alternative for the production of allograft tissues and organs to circumvent the incidences of donor scarcity and organ shortages. With the current deficit of readily available and viable organs for transplantation, the medical sector is faced with an increasing demand for organs and the shortfall in supply. Over the past decades, tissue engineering (TE) and regenerative medicine continue to provide alternative strategies for artificial tissues and organs. Current research shows that employing hydrogels as a cell-laden bioinks for the fabrication of 3D tissue constructs enables a lack of immunogenicity, since the hydrogel-based bioink is patient-specific and derived from biopolymers that demonstrate excellent biocompatibility and biodegradability, decreased organ rejection, increased organ viability, and enhanced the supply in accordance to the demand. While sufficient evidence directs researchers to conclude the safe and efficacious process of seeding cells, biomolecules, and biomaterials using 3D bioprinting, there are multiple limitations, which requires significant attention, such as cost, volumetric bioprinting, integrity, and strength of biomaterials, as well as multicellular and multimaterial bioprinting. In this review, the focus is on the applications of hydrogels as bioinks employed in 3D bioprinting and, where applicable, considerations of note and challenges encountered. This review proposes to highlight not only the progress forged in this area, but also the limitations of hydrogel-based bioink investigations to date and the need for further multidisciplinary investigation and progression to the stage of clinical testing of human-scale tissue constructs.
Previn Ramiah; Lisa C. Du Toit; Yahya E. Choonara; Pierre P. D. Kondiah; Viness Pillay. Hydrogel-Based Bioinks for 3D Bioprinting in Tissue Regeneration. Frontiers in Materials 2020, 7, 1 .
AMA StylePrevin Ramiah, Lisa C. Du Toit, Yahya E. Choonara, Pierre P. D. Kondiah, Viness Pillay. Hydrogel-Based Bioinks for 3D Bioprinting in Tissue Regeneration. Frontiers in Materials. 2020; 7 ():1.
Chicago/Turabian StylePrevin Ramiah; Lisa C. Du Toit; Yahya E. Choonara; Pierre P. D. Kondiah; Viness Pillay. 2020. "Hydrogel-Based Bioinks for 3D Bioprinting in Tissue Regeneration." Frontiers in Materials 7, no. : 1.
Recent research has been successful in demonstrating the importance of the addition of platelets to the field of cell-mediated therapeutics, by making use of different platelet forms to design modalities able to positively impact a wide range of diseases. A key obstacle hindering the success of conventional therapeutic interventions is their inability to produce targeted treatment, resulting in a number of systemic side effects and a longer duration for the onset of action to occur. An additional challenge facing current popular therapeutic interventions is biocompatibility of the system, resulting in the decline of patient compliance to treatment. In an attempt to address these challenges, the past few decades have been witness to the discovery and innovation of precision therapy, in order to achieve targeted treatment for an array of conditions, thereby superseding alternative mechanisms of treatment. Platelet-mediated therapeutics, as well as employing platelets as drug delivery vehicles, are key components in advancing precision therapy within research and in clinical settings. This novel approach is designed with the objective that the platelets retain their original structure and functions within the body, thereby mitigating biocompatibility challenges. In this article, we review the current significant impact that the addition of platelet-inspired systems has made on the field of therapeutics; explore certain limitations of each system, together with ideas on how to overcome them; and discuss the clinical implications and future potential of platelet-inspired therapeutics. Graphical
Sarah M. Kola; Yahya E. Choonara; Pradeep Kumar; Pierre P. D. Kondiah; Viness Pillay. Platelet-inspired therapeutics: current status, limitations, clinical implications, and future potential. Drug Delivery and Translational Research 2020, 11, 24 -48.
AMA StyleSarah M. Kola, Yahya E. Choonara, Pradeep Kumar, Pierre P. D. Kondiah, Viness Pillay. Platelet-inspired therapeutics: current status, limitations, clinical implications, and future potential. Drug Delivery and Translational Research. 2020; 11 (1):24-48.
Chicago/Turabian StyleSarah M. Kola; Yahya E. Choonara; Pradeep Kumar; Pierre P. D. Kondiah; Viness Pillay. 2020. "Platelet-inspired therapeutics: current status, limitations, clinical implications, and future potential." Drug Delivery and Translational Research 11, no. 1: 24-48.
Targeted and controlled drug delivery employing “smart materials” is a widely investigated field, within which stimuli-responsive polymers, particularly those which are thermo-responsive, have received considerable attention. Thermo-responsive polymers have facilitated the formulation of in situ gel forming systems which undergo a sol-gel transition at physiological body temperature, and have revolutionized the fields of tissue engineering, cell encapsulation, and controlled, sustained delivery of both drugs and genes. However, the use of single thermo-responsive polymers in the creation of these systems has posed numerous problems in terms of physico-mechanical properties, such as poor mechanical strength, high critical gelation concentrations (CGC) resulting in increased production costs and solutions that are too viscous, toxicity, as well as gelation temperatures that are incompatible with physiological body temperatures. Hybridization of these thermo-responsive polymers with other polymers has therefore been employed, resulting in the creation of tailor-made drug delivery systems that have optimal gelation temperatures and concentrations, ideal viscosities and improved gel strengths. This article reviews various thermo-responsive polymers that have been employed in the formulation of thermo-gelling systems. Special attention has been given to the hybridization of each of these polymers, the resulting systems that have been created, and their biomedical applications.
Taskeen Sarwan; Pradeep Kumar; Yahya E. Choonara; Viness Pillay. Hybrid Thermo-Responsive Polymer Systems and Their Biomedical Applications. Frontiers in Materials 2020, 7, 1 .
AMA StyleTaskeen Sarwan, Pradeep Kumar, Yahya E. Choonara, Viness Pillay. Hybrid Thermo-Responsive Polymer Systems and Their Biomedical Applications. Frontiers in Materials. 2020; 7 ():1.
Chicago/Turabian StyleTaskeen Sarwan; Pradeep Kumar; Yahya E. Choonara; Viness Pillay. 2020. "Hybrid Thermo-Responsive Polymer Systems and Their Biomedical Applications." Frontiers in Materials 7, no. : 1.
Currently, there is a lack of ultrasensitive diagnostic tool to detect some diseases such as ischemic stroke, thereby impacting effective and efficient intervention for such diseases at an embryonic stage. In addition to the lack of proper detection of the neurological diseases, there is also a challenge in the treatment of these diseases. Carbon nanotubes have a potential to be employed in solving the theragnostic challenges in those diseases. In this study, carbon nanotubes were successfully synthesized for potential application in the detection and treatment of the neurological diseases such as ischemic stroke. Vertically aligned multiwalled carbon nanotubes (VA-MWCNTs) were purified with HCl, carboxylated with H2SO4:HNO3 (3:1) and acylated with SOCl2 for use in potential targeting studies and for the design of a carbon-based electrode for possible application in the diagnosis of neurological diseases, including ischemic stroke. MWCNTs were washed, extracted from the filter membranes and dried in a vacuum oven at 60 °C for 24 h prior to functionalization and PEGylation. CNTs were characterized by SEM, TEM, OCA, DLS, CV and EIS. The HCl-treated CNT obtained showed an internal diameter, outer diameter and thickness of 8 nm, 34 nm and 75 µm, while these parameters for the H2SO4-HNO3-treated CNT were 8 nm, 23 nm and 41µm, respectively. PEGylated CNT demonstrated zeta potential, polydispersive index and particle size distribution of 6 mV, 0.41 and 98 nm, respectively. VA-MWCNTs from quartz tube were successfully purified, carboxylated, acylated and PEGylated for potential functionalization for use in targeting studies. For designing the carbon-based electrode, VA-MWCNTs on silicon wafer were successfully incorporated into epoxy resin for diagnostic applications. Functionalized MWCNTs were nontoxic towards PC-12 neuronal cells. In conclusion, vertically super-aligned MWCNTs have been successfully synthesized and functionalized for possible theragnostic biomedical applications in neurological disorders such as ischemic stroke.
Patrick P. Komane; Pradeep Kumar; Yahya E. Choonara; Viness Pillay. Functionalized, Vertically Super-Aligned Multiwalled Carbon Nanotubes for Potential Biomedical Applications. International Journal of Molecular Sciences 2020, 21, 2276 .
AMA StylePatrick P. Komane, Pradeep Kumar, Yahya E. Choonara, Viness Pillay. Functionalized, Vertically Super-Aligned Multiwalled Carbon Nanotubes for Potential Biomedical Applications. International Journal of Molecular Sciences. 2020; 21 (7):2276.
Chicago/Turabian StylePatrick P. Komane; Pradeep Kumar; Yahya E. Choonara; Viness Pillay. 2020. "Functionalized, Vertically Super-Aligned Multiwalled Carbon Nanotubes for Potential Biomedical Applications." International Journal of Molecular Sciences 21, no. 7: 2276.
There are many challenges involved in ocular drug delivery. These are a result of the many tissue barriers and defense mechanisms that are present with the eye; such as the cornea, conjunctiva, the blinking reflex, and nasolacrimal drainage system. This leads to many of the conventional ophthalmic preparations, such as eye drops, having low bioavailability profiles, rapid removal from the administration site, and thus ineffective delivery of drugs. Hydrogels have been investigated as a delivery system which is able to overcome some of these challenges. These have been formulated as standalone systems or with the incorporation of other technologies such as nanoparticles. Hydrogels are able to be formulated in such a way that they are able to change from a liquid to gel as a response to a stimulus; known as “smart” or stimuli-responsive biotechnology platforms. Various different stimuli-responsive hydrogel systems are discussed in this article. Hydrogel drug delivery systems are able to be formulated from both synthetic and natural polymers, known as biopolymers. This review focuses on the formulations which incorporate biopolymers. These polymers have a number of benefits such as the fact that they are biodegradable, biocompatible, and non-cytotoxic. The biocompatibility of the polymers is essential for ocular drug delivery systems because the eye is an extremely sensitive organ which is known as an immune privileged site.
Courtney R. Lynch; Pierre P. D. Kondiah; Yahya E. Choonara; Lisa C. Du Toit; Naseer Ally; Viness Pillay. Hydrogel Biomaterials for Application in Ocular Drug Delivery. Frontiers in Bioengineering and Biotechnology 2020, 8, 228 .
AMA StyleCourtney R. Lynch, Pierre P. D. Kondiah, Yahya E. Choonara, Lisa C. Du Toit, Naseer Ally, Viness Pillay. Hydrogel Biomaterials for Application in Ocular Drug Delivery. Frontiers in Bioengineering and Biotechnology. 2020; 8 ():228.
Chicago/Turabian StyleCourtney R. Lynch; Pierre P. D. Kondiah; Yahya E. Choonara; Lisa C. Du Toit; Naseer Ally; Viness Pillay. 2020. "Hydrogel Biomaterials for Application in Ocular Drug Delivery." Frontiers in Bioengineering and Biotechnology 8, no. : 228.
Routes of drug administration and their corresponding physiochemical characteristics play major roles in drug therapeutic efficiency and biological effects. Each route of delivery has favourable aspects and limitations. The oral route of delivery is the most convenient, widely accepted and safe route. However, the oral route of chemotherapeutics to date have displayed high gastric degradation, low aqueous solubility, poor formulation stability and minimum intestinal absorption. Thus, mainstream anti-cancer drugs in current formulations are not suitable as oral chemotherapeutic formulations. The use of biopolymers such as chitosan, gelatin, hyaluronic acid and polyglutamic acid, for the synthesis of oral delivery platforms, have potential to help overcome problems associated with oral delivery of chemotherapeutics. Biopolymers have favourable stimuli-responsive properties, and thus can be used to improve oral bioavailability of anti-cancer drugs. These biopolymeric formulations can protect gastric-sensitive drugs from pH degradation, target specific binding sites for targeted absorption and consequently control drug release. In this review, the use of various biopolymers as oral drug delivery systems for chemotherapeutics will be discussed.
Vanessa T. Chivere; Pierre P. D. Kondiah; Yahya E. Choonara; Viness Pillay. Nanotechnology-Based Biopolymeric Oral Delivery Platforms for Advanced Cancer Treatment. Cancers 2020, 12, 522 .
AMA StyleVanessa T. Chivere, Pierre P. D. Kondiah, Yahya E. Choonara, Viness Pillay. Nanotechnology-Based Biopolymeric Oral Delivery Platforms for Advanced Cancer Treatment. Cancers. 2020; 12 (2):522.
Chicago/Turabian StyleVanessa T. Chivere; Pierre P. D. Kondiah; Yahya E. Choonara; Viness Pillay. 2020. "Nanotechnology-Based Biopolymeric Oral Delivery Platforms for Advanced Cancer Treatment." Cancers 12, no. 2: 522.