Influence of chitosan and Cissus quandrangularis coating on osseointegration in titanium implants in rabbits: A preclinical in vivo study.

BACKGROUND: Titanium (Ti) implants has been criticized for the tiring wait for osseointegration, often making the patient reconsider implant treatment. Surface treated Ti implants are emerging as a promising solution with superior osseointegration, early loading protocols and shortened period of edentulousness. The aim of this study is to assess the osseointegration of Ti surface coated with novel Cissus quandrangularis Chitosan Hydrogel (CqChH) compared to Commercially pure (Cp) implants. METHODS: 24 Cp Ti implants were divided into 2 subgroups (n = 12). The test group consisted of Ti implants surface treated with the novel hydrogel and control group consisted of Cp Ti implants. 3 % CqChH was prepared and was coated on the Ti implants prior to placement in the femur and tibial heads of rabbits. Implant Stability Quotient (ISQ) was recorded at the 6th and 12th week. Animals were sacrificed and subjected to Removal Torque Quotient (RTQ). The samples were retrieved en bloc and stained for histopathologic analysis. The collected data was subjected to statistical analysis using Unpaired student t-Test. RESULTS: At the end of 6th week CqChH coated implants did not show any statistically significant difference in both ISQ and RTQ values compared to Cp ones. However, at the end of the 12th week CqChH coated implants demonstrated significantly higher ISQ (73.91 ± 4.39) and RTQ (75.96 ± 14.10) compared to Cp ones. CONCLUSIONS: This study demonstrated that the novel hydrogel coating applied to the implant's surface exhibited not only enhanced bone regeneration but also elicited a new bone formation.

Vaginal expression of efflux transporters and the potential impact on the disposition of microbicides in vitro and in rabbits.

In order to reach sufficiently high tissue concentrations and thus be effective, vaginally applied anti-HIV microbicides that are active at the level of the immune cells must permeate across the cervicovaginal mucosal layer. Cellular efflux transporters, such as Pgp, BCRP, and MRP-2, have been demonstrated to greatly affect drug disposition at different sites in the body including the intestine and the blood-brain barrier; their possible role on drug uptake from the female genital tract, however, has not been elucidated yet. In the present study, the protein expression of Pgp, BCRP, and MRP-2 in endocervical and vaginal tissue of premenopausal women was confirmed by Western blot analysis. To enable the assessment of transporter effects in vitro, the identification of an appropriate cervicovaginal cell line was pursued. The cervical SiHa cell line was observed to express mRNA of the 3 studied transporters, but only MRP-2 was found to be active. Consequently, the established Caco-2 cell line was utilized as an alternative in which the interaction of 10 microbicide candidates with the efflux transporters was studied. Darunavir, saquinavir, and maraviroc were identified as Pgp and MRP-2 substrates. The impact of Pgp on in vivo drug disposition was further examined for the model Pgp substrate talinolol in rabbits. Its vaginal uptake was significantly reduced by Pgp-mediated efflux when formulated in a neutral but not in an acidic gel. Our findings indicate the expression of a functional Pgp transporter in the vaginal mucosa that may severely reduce the vaginal uptake of Pgp substrates, including certain microbicide candidates, especially in women with an increased vaginal pH.

Development and characterization of a solid dispersion film for the vaginal application of the anti-HIV microbicide UAMC01398.

The purpose of this work was to design and evaluate a vaginal film delivery system for UAMC01398, a novel non-nucleoside reverse transcriptase inhibitor currently under investigation for use as an anti-HIV microbicide. UAMC01398 (1mg) films consisting of hydroxypropylmethylcellulose (HPMC) and polyethylene glycol 400 (PEG400) in different ratios were prepared by solvent evaporation. Based on its flexibility, softness and translucent appearance, the 30% PEG400 and 70% HPMC containing film was selected for further assessment. The vaginal film formulation was fast-dissolving (<10 min in 1 mL of vaginal fluid simulant), stable up to at least one month and safe toward epithelial cells and lactobacilli. Furthermore, formulating UAMC01398 into the film dosage form did not influence its antiviral activity. Powder X-ray diffraction revealed the amorphous nature of the UAMC01398 film, resulting in enhanced compound permeation across the epithelial HEC-1A cell layer, presumably owing to the induction of supersaturation. The in vivo vaginal tissue uptake of UAMC01398 in rabbits, as measured by systemic concentrations, was increased compared to the previously established non-solubilizing gel (significant difference) and sulfobutyl ether-ß-cyclodextrin (5%) containing gel. To conclude, we identified a film formulation suitable for the vaginal delivery of UAMC01398.