Design and in vitro evaluation of tenofovir-loaded vaginal gels for the prevention of HIV infections.

Infection with the human immunodeficiency virus (HIV) is affecting women disproportionally with increasing incidence rates over the last decades. Tenofovir is one of the most commonly used antiretroviral agents, which belongs to the nucleoside/nucleotide reverse transcriptase inhibitor family, for the prevention of HIV acquisition. In scope of this study, a thermogelling system containing tenofovir-loaded chitosan nanoparticles for the controlled release of tenofovir was developed and characterized. The in vitro release studies have shown that the burst release effect was decreased to 27% with f-TFV CS NPs-Gel. Gelation temperature of developed formulation was found as 26.6 ± 0.2 °C, which provides ease of administration while gelation occurs after the administration to the vagina. The work of adhesion values was used as parameters for comparison of mucoadhesive performance and the mucoadhesion of f-TFV CS NPs-Gel was found as 0.516 ± 0.136 N.s at 37 °C. The biocompatibility of blank formulations was evaluated by cell viability studies using L929 cells, in which Gel + CS NPs formulation was found to be safe with 82.4% and 90.2% cell viability for 1:16 and 1:32 dilutions, respectively. In conclusion, an improved tenofovir containing vaginal gel formulation was successfully developed and evaluated for preventing HIV transmission.

Design and In Vitro Evaluation of Bispecific Complexes and Drug Conjugates of Anticancer Peptide, LyP-1 in Human Breast Cancer.

PURPOSE: LyP-1, a nine-amino-acid tumor homing peptide, selectively binds to its cognate receptor, p32. Overexpression of p32 in certain tumors should allow use of LyP-1 as a targeting agent for the delivery of therapeutic or diagnostic agents. Peptide conjugates are developed for enhanced pre-targeting of MDA-MB-231 breast cancer cells with peptide-antibody bispecific complexes and targeting with multiple-drug/-fluorophore-conjugated nano-polymers. METHODS: LyP-1-anti-DTPA bispecific antibody complexes (LyP-1-bsAbCx) were generated by conjugation of anti-DTPA antibody and LyP-1. LyP-1-doxorubicin (Dox), Dox-DTPA-succinyl-polylysine (Dox-DSPL), Dox-DSPL-LyP-1, DTPA-Dox-poly glutamic acid (D-Dox-PGA) or DTPA-rhodamine conjugated polylysine (DSPL-RITC) were prepared. In vitro therapeutic efficacy and targeting by immunofluorescence in MDA-MB-231 breast cancer cells were assessed with Dox-LyP-1. Immunofluorescence visualization of cancer cells was evaluated after pretargeting with LyP-1-bsAbCx and targeting with DSPL-RITC. RESULTS: Cytotoxicity of Dox-LyP-1 conjugates was significantly greater than free doxorubicin (p < 0.0001). For fluorescent-labeled LyP-1, internalization occurred in 30 min in tumor cells. Fluorescence intensity of two-step targeted cells showed that pretargeting with LyP-1-bsAbC, followed by targeting with DSPL-RITC was greater than non-pretargeted DSPL-RITC (p < 0.05). CONCLUSIONS: Peptide-conjugates are effective targeting agents for MDA-MB-231 breast cancer cells in culture. LyP-1-bsAbCx and Dox-LyP-1 conjugates may allow development of novel targeted cancer therapy and diagnosis.

Effect of topically applied sildenafil citrate on wound healing: experimental study.

Wound healing is a complex process that necessitates organization of different cell types and several signalling molecules. The aim of this study is to evaluate the effect of different concentrations of sildenafil citrate, which decreases cGMP degradation, on wound healing by secondary intention.This study was performed using 25 Sprague Dawley rats weighing 200-250 grams. 4 dorsal defects were created. Four different treatment modalities which were 1% and 5% sildenafil citrate gel prepared with carbopol, pure carbopol gel without any drug in it and 0,9% NaCl solution; were applied to each lesion of the same rat. Randomly selected five rats (25 rats in total) were sacrificed on 3rd, 5th, 7th, 10th, and 14th days; and the effect of each modality was evaluated by means of defect area measurement, histopathological examination and measurement of tissue hydroxyproline levels.Sildenafil citrate gel application decreased the defect areas in a dose independent manner starting from 3rd day and dose dependent manner after 7th day. By means of vascularization, sildenafil citrate increased vascularity starting from 3rd day. The strength of acute inflammation was superior in sildenafil groups starting from 5th day; and the amount and maturation of granulation in the wound bed, as well as the strength of chronic inflammation were superior in defects treated with sildenafil citrate as early as 7th day.

Design and characterization of nanocrystal formulations containing ezetimibe.

Ezetimibe is a lipid-lowering compound that selectively inhibits the absorption of cholesterol and related phytosterols from the intestine. As ezetimibe is almost insoluble in water, its bioavailability is too low to be detected. Thus, the objective of this study was to improve the solubility and dissolution rate of ezetimibe by preparing drug nanocrystals utilizing ball milling, high speed homogenization techniques. Pluronic F127 was chosen as a surface modifier to stabilize the nanocrystal formulations. Nanocrystal formulations of ezetimibe were prepared by using ball milling and high speed homogenization techniques. Additionally, the physicochemical characteristics of ezetimibe and nanocrystal formulations were determined by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray analysis and particle size analysis. Tablets were prepared containing ezetimibe nanocrystals formed by high speed homogenization (ultrasonic) and ball milling according to the results of particle size measurements and in vitro dissolution rates of the nanocrystal formulations. As a result of these experiments, it was found that the dissolution rate of the nanocrystal formulations increased and although tablet formulations which did not contain any solubilizing agent like sodium lauryl sulfate (SDS), the dissolution profile of these formulations were found similar to the commercial product.