Purpose The aim of this study was to prepare fluconazole (FLC) nanoparticles coated with polyethylene glycol (PEG) in the form of FLC-PEG-NPs and optimize the size and entrapment efficiency. Methods Nine formulae were prepared by solvent antisolvent precipitation technique according to full 3 2 factorial designs. The effects of PEG molecular weight (X 1 ) and the drug polymer ratio (X 2 ) on the particle size (Y 1 ) and entrapment efficiency (Y 2 ) were explored. The prepared FLC-PEG-NPs were investigated for particle size, count rate, PDI, zeta potential, and morphology. Carbopol hydrogel was prepared, loaded with optimized FLC-PEG-NPs, and characterized for pH, FLC content, viscosity, homogeneity and spreadability, in vitro release, skin permeation, and antifungal activity. Results The formulated nanoparticles were uniform in size and spherical in shape with slightly rough surface and free from aggregations. The effect of PEG molecular was antagonistic on the particle size and was agonistic on EE %. The release of drug from hydrogel containing pure FLC was always lower than that from hydrogel containing FLC-PEG-NPs. The kinetic analysis of drug release obeys first-order release model and super case II transport mechanism. The cumulative amount of drug permeated applying hydrogel containing optimized FLC-PEG-NPs was significantly higher than the amount permeated using pure fluconazole containing hydrogel. The antifungal activity of hydrogel containing FLC in the form of optimized PEG-coated nanoparticles was better than hydrogel containing pure drug as indicated by relatively high inhibition zone using agar well-diffusion method. Conclusion Small spherical FLC nanoparticles with enhanced in vitro drug release as well as improved antifungal activity could be achieved by using PEG-coated fluconazole nanoparticles.
Objective
To enhance bioavailability of timolol (TML) and utilize alternatives for traditional eye drops for more patient compliance, this study was aiming to develop biodegradable orally dissolving strips (ODSs) of TML for treatment of primary open‐angle glaucoma (POAG).
Methods
Novel ODSs of TML were formulated and optimized using solvent casting method according to full factorial design (31.22). TML ODSs were characterized with respect to many parameters. In‐vivo test was carried out using four groups of 24 New Zealand albino rabbits. POAG was induced by subconjunctival treatment of betamethasone. Histopathological examination and oxidative stress markers assay were carried out.
Key findings
The optimized formula (F9) exhibited a remarkably 15‐s disintegration time and 96% dissolution rate after 10 min. The results revealed a potent significant inhibitory effect of the optimized TML ODS to reduce IOP in induced rabbits in comparison with control rabbits and TML eye drops‐treated rabbits. The formula showed also high activity against oxidative stress and absence of histopathological changes in iridocorneal angle and cornea.
Conclusion
The ODSs could be a promising alternative delivery system for eye drops with more compliance to enhance delivery and therapeutic activity of TML in treatment of POAG.
Resveratrol (RSV), a non-flavonoid stilbene polyphenol, possesses anti-carcinogenic activities against all the major stages of cancer. Zein nanoparticles (ZN NPs) have been utilized successfully in delivery of variant therapeuticals by virtue of their histocompatible nature. The goal of this work was to comparatively explore the antiproliferative, pro-apoptotic and oxidative stress potentials of RSV-ZN NPs versus RSV against human colorectal carcinoma HCT-116 cells. ZN-RSV NPs were developed and assayed for particle size analysis and RSV diffusion. The selected formula obtained 137.6 ± 8.3 nm as mean particle size, 29.4 ± 1.8 mV zeta potential, 92.3 ± 3.6% encapsulation efficiency. IC50 of the selected formula was significantly lower against HCT-116 cells versus Caco-2 cells. Also, significantly enhanced cellular uptake was generated from RSV-ZN NPs versus free RSV. Enhanced apoptosis was concluded due to increased percentage cells in G2-M and pre-G1 phases. The pro-apoptotic potential was explained by caspase-3 and cleaved caspase-3 increased mRNA expression in addition to NF-κB and miRNA125b decreased expression. Biochemically, ZN-RSV NPs induced oxidative stress as demonstrated by enhanced reactive oxygen species (ROS) generation and endothelial nitric oxide synthase (eNOS) isoenzyme increased levels. Conclusively, ZN-RSV NPs obtained cell cycle inhibition supported with augmented cytotoxicity, uptake and oxidative stress markers levels in HCT-116 tumor cells in comparison with free RSV. These results indicated intensified chemopreventive profile of RSV due to effective delivery utilizing ZN nano-dispersion against colorectal carcinoma HCT-116 cells.
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