pH-responsive nanoparticles releasing tenofovir intended for the prevention of HIV transmission

Abstract

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.

Cationic PLGA/Eudragit RL nanoparticles for increasing retention time in synovial cavity after intra-articular injection in knee joint

“…26 In brief, 330 μL of DiR-encapsulated NP suspension and/or the aggregates contained in a dialysis bag was loaded to 60 mL of 1% (w/v) SLS-containing PBS solution (pH 7.4) at 37°C and rotated at 100 rpm. At scheduled intervals, 300 μL of the release medium was collected for the fluorescence assay (Flex station 3 microplate reader, Molecular Devices), with the excitation and emission wavelength selected at 748 and 792 nm, respectively.…”

Polyurethane/Poly(2-(Diethyl Amino)Ethyl Methacrylate) blend for drug delivery applications

“…Blends have many applications, but in particular they are being proposed for using in drug delivery based on polymers [2][3][4] ; or on composites [5] . pH-sensitive systems are a particular case and several materials were proposed for preparing them, including silica particles [6,7] , other inorganic particles [8] , polymeric blends [9][10][11][12] , copolymers [13][14][15] and hybrid materials [16,17] .…”

Novel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+ immune cells

“…For example, Zhang et al developed a pH-responsive NP formulation that can achieve increased sustained release of tenofovir in acidic environments as a potential intravaginal microbicide. 43 Das Neves et al also compared different types of polymeric NPs for delivering dapivirine as a microbicide, in terms of efficacy and cytotoxicity in various HIV-related cells. 44 Woodrow et al developed an intravaginal delivery system that can effectively silence herpes simplex virus genes with small interfering RNA.…”