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 was 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. Drug release from medium (281 nm) and large size (602 nm)-sized NPs fitted the Higuchi (r2=0.991) and first-order release (r2=0.999) models, respectively. These NPs were not cytotoxic to both the vaginal epithelial cell line and Lactobacillus for 48 hours. When the diameter of the NPs decreased from 900 nm to 188 nm, the mucoadhesion increased from 6% to 12%. However, the combinatorial effect of EE% × 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.

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This study is designed to test the hypothesis that Tenofovir(TNF)ortenofovir disoproxil fumarate (TDF) loaded nanoparticles (NPs)prepared with a blend of poly(lactic-co-glycolic acid) (PLGA) and methacrylic acid copolymer (Eudragit® S-100, or S-100)are noncytotoxic and exhibit significant pH-responsive release of anti-HIV microbicides in presence of human semen. After NPs preparation by emulsification diffusion, their size, encapsulation efficiency (EE%), drug release profile, morphology, and cytotoxicity are characterized by dynamic light scattering, spectrophotometry, transmission electron microscopy, and cellular viability assay/transepithelial electrical resistance measurement, respectively. Cellular uptake was elucidated by fluorescence spectroscopy and confocal microscopy. The NP shavean average size of 250 nm, maximal EE% of 16.1% and 37.2% for TNF and TDF, respectively. There is a 4-fold increase in the drug release rate from 75% S-100 blendin the presence of semen fluid simulant over 72 hr. At a concentration up to 10 mg/ml, the PLGA/S-100 NPs are noncytotoxic for 48 hr to vaginal endocervical/epithelial cells and Lactobacillus crispatus. The particle uptake (~50% in 24hr.) by these vaginal cell lines mostly occurred through caveolin-mediated pathway. These data suggest the promise of using PLGA/S-100 NP as an alternative controlled drug delivery system in intravaginal delivery of an anti-HIV/AIDS microbicide.

Once metastatic, melanoma remains one of the most aggressive and morbid malignancies. Moreover, in past decades, the overall survival for advanced unresectable melanoma exhibited a constancy of poor prognosis. Low response rates and serious adverse effects have been characteristic of standard therapy based on a combination of chemotherapeutic agents or immunotherapy with IL-2. For example, the chemotherapy including dacarbazine, carmustin, cisplatin and tamoxifen is known as ‘Dartmouth regimen’ while the CVD regimen comprises carmustine, vinblastine and dacarbazine. Thus, there is an urgent and critical need to reformulate these bioactive agents using nanoscience and nanotechnology as alternative strategies. This article overviews current design and evaluation of nanomedicine undertaken to address this unmet medical need. The nanomedicines studied include polymeric nanoparticles, liposomes, polymersomes, dendrimers, cubosomes, niosomes and nanodiamonds. In this preclinical article, nanotechnology provides hope for effective treatment of this aggressive and largely treatment-resistant disease.