Resveratrol (RES) is a naturally existing polyphenol which exhibits anti-oxidant, anti-inflammatory, and anti-cancer properties. In recent years, RES has attracted attention for its synergistic effect with other anti-cancer drugs for the treatment of drug resistant cancers. However, RES faces the issues of poor pharmacokinetics, stability and low solubility which limits its clinical application. In present study, RES has been loaded onto uniformly sized (~60 nm) mesoporous silica nanoparticles (MSNs) to improve its in vitro anti-proliferative activity and sensitization of Docatexal in hypoxia induced drug resistance in prostate cancer. RES was efficiently encapsulated within phosphonate (negatively charged) and amine (positively charged) modified MSNs. The effect of surface functionalization was studied on the loading, in vitro release, anti-proliferative and cytotoxic potential of RES using prostate cancer cell line. At pH 7.4 both free and NH₂-MSNs loaded RES showed burst release which was plateaued with almost 90% of drug released in first 12 h. On the other hand, PO₃-MSNs showed significantly slower release kinetics with only 50% drug release in first 12 h at pH 7.4. At pH 5.5, however, both the PO₃-MSNs and NH₂-MSNs showed significant control over release (around 40% less release compared with free RES in 24 h). Phosphonate modified MSNs significantly enhanced the anti-proliferative potential of RES with an IC₅₀ of 7.15 μM as compared to 14.86 μM of free RES whereas amine modified MSNs didn't affect proliferation with an IC₅₀ value higher than free RES (20.45 μM). Furthermore, RES loaded onto PO₃-MSNs showed robust and dose dependent sensitization of Docatexal in hypoxic cell environment which was comparable to pure RES solution. This study provides an example of applicability of MSNs loaded with polyphenols such as RES as next generation anticancer formulations for treating drug resistant cancers such as prostate cancer.

Photoacoustic (PA) imaging is gaining momentum due to its greater depth of field, low background, and 3D imaging capabilities. However, traditional PA imaging agents (e.g. dyes, quantum dots, etc.) are usually unstable in plasma and bind to serum proteins, and thus cleared rapidly. Because of this, the nanoparticle encapsulation of PA imaging agents is becoming increasingly popular. Therefore, the rational design of carrier nanoparticles for this purpose is necessary for strong imaging signal intensity, high biosafety, and precise targeting. Herein, we systematically evaluate the influence of the chemical and physical surface functionalization of mesoporous silica nanoparticles (MSNs) on the photo-stability, loading, release, and photoacoustic (PA) signal strength of the FDA approved small molecule contrast agent, indocyanine green (ICG). Chemical functionalization involved the modification of MSNs with silanes having amine (NH₂) or phosphonate (PO₃) terminal groups, whereas physical modifications were performed by capping the ICG loaded MSNs with lipid bilayer (LB) or layer-by-layer (LBL) polyelectrolyte coatings. The NH₂-MSNs display the highest ICG mass loading capacity (16.5 wt%) with a limited release of ICG (5%) in PBS over 48 h, while PO₃-MSNs only loaded ICG around 3.5 wt%. The physically modified MSNs (i.e. LBMSNs and LBLMSNs) were vacuum loaded resulting in approximately 9 wt% loading and less than 10% ICG release in 48 h. Pure ICG was highly photo-unstable and showed 20% reduction in photoluminescence (PL) within 3 h of exposure to 800 nm, while the ICG loaded onto functionalized MSNs did not photo-degrade. Among the tested formulations, NH₂-MSNs and LBLMSNs presented 4-fold in vitro PA signal intensity enhancement at a 200 μg mL⁻¹ equivalent ICG dose. Similar to the in vitro PA imaging, NH₂-MSNs and LBLMSNs performed the best when subcutaneously injected into mouse cadavers with 1.29- and 1.43-fold PA signal enhancement in comparison to the pure ICG, respectively.

This study evaluated the effect of solubilized and dispersed bacterial cellulose (BC) on the physicochemical characteristics and drug release profile of hydrogels synthesized using biopolymers. Superabsorbent hydrogels were synthesized by graft polymerization of acrylamide on BC solubilized in an NaOH/urea solvent system and on dispersed BC by usingN,N′-methylenebisacrylamide as a crosslinker under microwave irradiation. Fourier transform infrared spectroscopy analysis of the resulting hydrogels confirmed the grafting, and an X-ray diffraction pattern showed a decrease in the crystallinity of BC after the grafting process. The hydrogels exhibited pH and ionic responsive swelling behavior, with hydrogels prepared using solubilized BC (SH) having higher swelling ratios. Furthermore, compared to the hydrogels synthesized using dispersed BC, the hydrogels synthesized using solubilized BC showed higher porosity, drug loading efficiency, and release. These results suggest the superiority of the hydrogels prepared using solubilized BC and that they should be explored further for oral drug delivery.

Type 2 diabetes makes up approximately 85% of all diabetic cases and it is linked to approximately one-third of all hospitalisations. Newer therapies with long-acting biologics such as glucagon-like peptide-1 (GLP-1) analogues have been promising in managing the disease, but they cannot reverse the pathology of the disease. Additionally, their parenteral administration is often associated with high healthcare costs, risk of infections, and poor patient adherence associated with phobia of needles. Oral delivery of these compounds would significantly improve patient compliance; however, poor enzymatic stability and low permeability across the gastrointestinal tract makes this task challenging. In the present work, large pore dendritic silica nanoparticles (DSNPs) with a pore size of ~10 nm were prepared, functionalized, and optimized in order to achieve high peptide loading and improve intestinal permeation of exenatide, a GLP-1 analogue. Compared to the loading capacity of the most popular, Mobil Composition of Matter No. 41 (MCM-41) with small pores, DSNPs showed significantly high loading owing to their large and dendritic pore structure. Among the tested DSNPs, pristine and phosphonate-modified DSNPs (PDSNPs) displayed remarkable loading of 40 and 35% w/w, respectively. Furthermore, particles successfully coated with positively charged chitosan reduced the burst release of exenatide at both pH 1.2 and 6.8. Compared with free exenatide, both chitosan-coated and uncoated PDSNPs enhanced exenatide transport through the Caco-2 monolayer by 1.7 fold. Interestingly, when a triple co-culture model of intestinal permeation was used, chitosan-coated PDSNPs performed better compared to both PDSNPs and free exenatide, which corroborated our hypothesis behind using chitosan to interact with mucus and improve permeation. These results indicate the emerging role of large pore silica nanoparticles as promising platforms for oral delivery of biologics such as exenatide.