Photocatalytic degradation of nevirapine with a heterostructure of few-layer black phosphorus coupled with niobium (V) oxide nanoflowers (FL-BP@Nb2O5).

The degradation and removal of antiviral drugs in water has emerged remains a major challenge. This work presents, the photodegradation of nevirapine (NVP) with a novel p-n heterostructure of FL-BP@Nb2O5 nanoparticles synthesized via hydrothermal method. Several characterization techniques revealed a successful formation of the heterostructure with well aligned band positions that promoted excellent separation of charge carriers. A systematic study was conducted on the effect of initial pH, initial catalyst loading and initial concentration on the degradation kinetics of NVP. Degradation efficiency of 68% was achieved with the FL-BP@Nb2O5 after 3 h with 5 ppm initial concentration solution of NVP, at a working pH of 3 and 15 mg of photocatalyst. The stable fragment resulting from the degradation of NVP was n-butanol as evidenced by LC/MS. The successful degradation of NVP transpired with synergistic effect exhibited by the heterostructure that led to accelerated formation of reactive species that were responsible for the breaking down of NVP into smaller fragments. A TOC removal percentage of 19.03% after the photodegradation of NVP was observed, suggesting a successful break down of NVP to simpler non-toxic carbon-containing compounds.

Nevirapine induces testicular toxicity in Wistar rats: reversal effect of kolaviron (biflavonoid from Garcinia kola seeds).

BACKGROUND: Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used in the treatment of HIV infections and has been reported to be toxic to the male reproductive system. This study was designed to evaluate the ameliorative effects of kolaviron (KV), a biflavonoid from Garcinia kola, on NVP-induced testicular toxicity. METHODS: The adult male Wistar rats were given two and four times therapeutic doses of NVP (NVP-2T and NVP-4T; 18 and 36 mg/kg NVP) alone or in combination with KV (200 mg/kg). NVP was given daily, whereas KV was administered five times in a week by oral gavage. RESULTS: Treatment with NVP did not alter the body weight gain and relative weight of testis of the rats. NVP-4T significantly (p<0.05) decreased the sperm motility, protein content, and live-dead ratio and also increased the percentage sperm abnormalities of the rats. Although NVP-4T significantly increased sperm abnormalities, it has no effect on epididymal sperm count. Also, NVP-4T caused a significant (p<0.05) elevation of serum aminotransferases and γ-glutamyl transferase activities. In addition, NVP-4T significantly (p<0.05) decreased the levels of testicular superoxide dismutase, catalase, glutathione S-transferase, and glutathione with marked elevation of malondialdehyde (index of lipid peroxidation) in the rats. In contrast, NVP-2T did not produce an adverse effect on the biochemical indices studied in testes and sperm of rats. Supplementation with KV significantly ameliorated the biochemical changes caused by NVP-4T. CONCLUSIONS: Taken together, KV reversed the adverse effects of NVP-4T on testicular antioxidant enzymes and markers of oxidative stress in the rats.

Design and development of nevirapine loaded surfactant free chitosan microemulsion.

Emulsification of liquid paraffin oil in aqueous solutions of chitosan without adding any additional surfactant is studied. The main objective of this study was to evaluate the dispersion of castor oil in aqueous phase in the presence of chitosan, and how this polymer promotes the stability of the obtained emulsions. Nevertheless, chitosan promotes emulsion production by increasing the matrix viscosity and provides stabilization of the oil-water interface by forming a dense hydrophilic polyelectrolytic brush on the water side of interface, which presents a significant barrier for coalescence--both steric and electrostatic. Chitosan stabilizes the emulsion mainly by the steric effect. These steric effects generate Van der Waals repulsion forces when two particles are too close. After loading with antiviral drug nevirapine, these emulsions were characterized in terms of phase contrast microscopy, hot stage microscopy, fluorescence microscopy, particle size, zeta potential, viscosity, entrapment efficiency and release studies using dialysis bag method. The prepared emulsions were stable in terms of mean globule size, change in drug content and retain they cationicity. The formulated emulsions are a promising carrier for nevirapine and other lipophilic drugs.

Non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors: past, present, and future perspectives.

Along with nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) have gained a definitive and important place in the treatment of HIV-1 infections, and are in rapid development. These compounds can be grouped into two classes: the first generation NNRTIs, mainly discovered by random screening, and the second generation NNRTIs, developed as a result of comprehensive strategies involving molecular modelling, rationale-based drug synthesis, biological and pharmacokinetic evaluations. The recent boom of NNRTIs is mainly due to their antiviral potency, high specificity and low toxicity. The rapid emergence of drug-resistant HIV-1 strains induced by the first generation drugs is a disadvantage bypassed, in part, by the broad spectrum second generation NNRTIs. Starting from the first generation, this review will focus on the second generation NNRTIs dealing with the recent and most interesting published results, highlighting the guidelines for the development of a third generation of NNRTIs.

Novel nonnucleoside inhibitors of HIV-1 reverse transcriptase. 8. 8-Aryloxymethyl- and 8-arylthiomethyldipyridodiazepinones.

Nevirapine (I) is the first human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitor to reach regulatory approval. As a result of a second generation program around the tricyclic core system of nevirapine, 2-chloro-5, 11-dihydro-11-ethyl-5-methyl-8-(2-(pyridin-4-yl)ethyl)-6H-dipyrido[3, 2-b:2',3'-e][1,4]diazepin-6-one (II)1a and 2-chloro-5, 11-dihydro-11-ethyl-5-methyl-8-phenylethyl-6H-dipyrido[3,2-b:2', 3'-e][1,4]diazepin-6-one (III)1a were identified as broad spectrum HIV-1 RT inhibitors. A detailed examination of replacing either of the methylenes of the 8-ethyl linker of II or III is presented. It was found that 8-aryloxymethyl and 8-arylthiomethyl are the preferred pattern of substitution for potency against RT. The most potent compounds were further evaluated against a panel of clinically significant mutant RT enzymes (K103N, V106A, G190A, P236L) and in cytotoxicity and in vitro metabolism assays. The most potent compound was 2-chloro-8-phenylthiomethyl analogue 37 which displayed sub-100 nM activity against all HIV-1 RT enzymes tested.