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

Abstract

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.

Mucosal Applications of Poloxamer 407-Based Hydrogels: An Overview

“…Timur et al combined the mucoadhesive properties of chitosan and the thermo-sensitive characteristics of poloxamer 407, in order to develop a thermo-gelling system containing chitosan nanoparticles for the vaginal delivery of tenofovir (TFV), an antiviral agent that is used in the treatment of the human immunodeficiency virus (HIV) [ 130 ]. An amount of TFV was entrapped in the gel, with the aim of controlling the leakage of drugs from the nanoparticles.…”

“…Both of these values were dramatically better than that obtained by the drug solution, which evidenced full leakage of the active compound over a 3 h period. The entrapment of TFV within the nanoparticles retained by the poloxamer-gel had two peculiar features: (1) the burst-release effect, induced by the presence of the free drug within the gel network, and (2) sustained drug leakage for up to 24 h due to the presence of the colloidal systems in the polymeric matrix [ 130 ].…”

Modifying the Properties of Thermogelling Poloxamer 407 Solutions through Covalent Modification and the Use of Polymer Additives

“…Thermogelling solutions containing tenofovir (TFV), an antiretroviral agent for the prevention of HIV acquisition, loaded into chitosan nanoparticles was prepared by Timur et al The P407 formulation containing chitosan nanoparticles had a Tgel of 26.6 °C which is slightly lower than the P407 20% w/v formulation with TFV only which was 28.2 °C . At 35 °C, the formulation containing nanoparticles had higher viscosity than the gel with the TFV only (100.24 Pa s and 87.8 Pa s, respectively) …”

“…Out of necessity, the findings have been simplified and the original articles should be consulted to fully understand the findings. Most studies report a decrease in Tgel when polymer or nanoparticle additives are incorporated into P407 solutions, which may be a result of the increased overall solute content. Whilst some studies report an increase in Tgel, this occurs only at lower (≈15% w/v) P407 concentration and low (≈<0.1% w/v) additive concentration.…”

Expansible thermal gelling foam aerosol for vaginal drug delivery

“…It is reported that prolonged carrier retention and extended drug release could be achieved by gel because of its better mucosal adhesion and superior gel strength (Mei et al, 2017;Timur et al, 2017;Tugcu-Demiroz, 2017). However, the application of gel in vaginal drug delivery is limited by its low penetration efficiency to the deep vaginal rugae because of its high viscoelasticity (Caramella et al, 2015;Johal et al, 2016).…”