Jianing Meng

Engineering Tenofovir Loaded Chitosan Nanoparticles: To Maximize Microbicide Mucoadhesion

The objective of this study was to engineer a model anti-HIV microbicide (tenofovir) loaded chitosan based nanoparticles (NPs). Box-Behnken design allowed to assess the influence of formulation variables on the size of NPs and drug encapsulation efficiency (EE%) that were analyzed by dynamic light scattering and UV spectroscopy, respectively. The effect of the NPs on vaginal epithelial cells and Lactobacillus crispatus viability and their mucoadhesion to porcine vaginal tissue were assessed by cytotoxicity assays and fluorimetry, respectively. In the optimal aqueous conditions, the EE% and NPs size were 5.83% and 207.97nm, respectively. With 50% (v/v) ethanol/water as alternative solvent, these two responses increased to 20% and 602 nm, respectively. Unlike small size (182nm) exhibiting burst release, drug release from medium (281 nm) and large (602 nm)-sized NPs fitted the Higuchi (r(2)=0.991) and first-order release (r(2)=0.999) models, respectively. These NPs were not cytotoxic to both the vaginal epithelial cell line and L. crispatus for 48h. When the diameter of the NPs decreased from 900 to 188 nm, the mucoadhesion increased from 6% to 12%. However, the combinatorial effect of EE% and percent mucoadhesion for larger size NPs was the highest. Overall, large-size, microbicide loaded chitosan NPs appeared to be promising nanomedicines for the prevention of HIV transmission.

Comparative biophysical properties of tenofovir-loaded, thiolated and nonthiolated chitosan nanoparticles intended for HIV prevention.

AIM This study is designed to test the hypothesis that tenofovir-loaded (an anti-HIV microbicide) chitosan-thioglycolic acid-conjugated (CS-TGA) nanoparticles (NPs) exhibit superior biophysical properties for mucoadhesion compared with those of native CS NPs. MATERIALS & METHODS The NPs are prepared by ionotropic gelation. The particle mean diameter, encapsulation efficiency and release profile are analyzed by dynamic light scattering and UV spectroscopy, respectively. The cytotoxicity, cellular uptake and uptake mechanism are assessed on VK2/E6E7 and End1/E6E7 cell lines by colorimetry/fluorimetry, and percentage mucoadhesion is assessed using porcine vaginal tissue. RESULTS The mean diameter of the optimal NP formulations ranges from 240 to 252 nm, with a maximal encapsulation efficiency of 22.60%. Tenofovir release from CS and CS-TGA NPs follows first-order and Higuchi models, respectively. Both NPs are noncytotoxic in 48 h. The cellular uptake, which is time dependent, mainly occurs via the caveolin-mediated pathway. The percentage of mucoadhesion of CS-TGA NPs is fivefold higher than that of CS NPs, and reached up to 65% after 2 h. CONCLUSION Collectively, CS-TGA NPs exhibit superior biophysical properties and can potentially maximize the retention time of a topical microbicide, such as tenofovir, intended for the prevention of HIV transmission.

Advances in Targeted Drug Delivery Approaches for the Central Nervous System Tumors: The Inspiration of Nanobiotechnology

At present, brain tumor is among the most challenging diseases to treat and the therapy is limited by the lack of effective methods to deliver anticancer agents across the blood-brain barrier (BBB). BBB is a selective barrier that separates the circulating blood from the brain extracellular fluid. In its neuroprotective function, BBB prevents the entry of toxins, as well as most of anticancer agents and is the main impediment for brain targeted drug delivery approaches. Nanotechnology-based delivery systems provide an attractive strategy to cross the BBB and reach the central nervous system (CNS). The incorporation of anticancer agents in various nanovehicles facilitates their delivery across the BBB. Moreover, a more powerful tool in brain tumor therapy has relied surface modifications of nanovehicles with specific ligands that can promote their passage through the BBB and favor the accumulation of the drug in CNS tumors. This review describes the physiological and anatomical features of the brain tumor and the BBB, and summarizes the recent advanced approaches to deliver anticancer drugs into brain tumor using nanobiotechnology-based drug carrier systems. The role of specific ligands in the design of functionalized nanovehicles for targeted delivery to brain tumor is reviewed. The current trends and future approaches in the CNS delivery of therapeutic molecules to tumors are also discussed.

Application of Design of Experiment and Simulation Methods to Liquid Chromatography Analysis of Topical HIV Microbicides Stampidine and HI443

This study intended to determine if experimental design and Monte Carlo simulation methods can be utilized to optimize the liquid chromatography (LC) analysis of active molecules. The method was applied for the simultaneous analysis of two topical microbicides, stampidine (STP) and HI443 in bulk and nanoformulations. The Plackett-Burman design was used for screening; whereas, Box-Behnken design was used to evaluate the main and interaction effects of the selected factors on the responses, namely peak area of STP (Y1), HI443 (Y2), tailing of STP (Y3), and HI443 (Y4). The Monte Carlo simulation was applied to get the minimum defect rate (DR) of the process. The optimized LC conditions were found to be X1; flow rate: 0.6 mL/min, X2; injection volume: 18 μL, and X3; initial gradient acetonitrile ratio: 92% v/v with a minimal DR of 0.077%. The optimized method was applied to determine the percent encapsulation efficiency (%EE) and in vitro release profile of STP and HI443 from solid lipid nanoparticles (SLNs). The %EE of STP and HI443 in SLNs was found to be 30.56 ± 9.44 and 94.80 ± 21.90% w/w, respectively, (n=3). It was observed that the release kinetics of STP followed the first order, whereas, HI443 followed the Peppas kinetic model in SLNs. The LC method was also applied for the estimation of molar extinction coefficients (ε270) of both drugs for the first time. These values were estimated to be 7,569.03 ± 217.96 and 17,823.67 ± 88.12 L/mol/cm for STP and HI443, respectively, (n=3). The results suggest that experimental design and Monte Carlo simulation can be effectively used to reduce the DR of a process and to optimize the chromatographic conditions for the analysis of bio-active agents as applied in this study.

Electrospun Nanofibers in Drug Delivery: Fabrication, Advances, and Biomedical Applications

Abstract Nanotechnology is an expanding and exciting technology. It has emerged as a vital scientific and commercial engine providing global economic benefits. With expanding knowledge of nanomaterials manufacturing techniques, research groups around the globe are focused more on the preparation of novel nanomaterials for various applications. Among the various techniques reported in the literature, electrospinning has gathered significant momentum due to its ability to fabricate nanostructures with unique properties such as a high surface area and inter/intrafibrous porosity. Electrospinning has been the most widely used technique in the 20th and early 21st centuries. Since its first application in the early 20th century, significant improvements have been made in the design, fabrication, and utility of the nanomaterials. The production of nanofibers via electrospinning is dependent on many operating parameters. This chapter provides an overview of the electrospinning (applied electric field, distance between the needle and collector, as well as flow rate and needle diameter), solution (polymer concentration, viscosity, solvent and solution conductivity), and environmental (relativity humidity and temperature) parameters. All of these parameters are crucial for the application of nanofibers in tissue engineering, drug delivery systems, wound dressings, antibacterial study, filtration, biosensors, and immunoassay.