RESUMEN

This study aims to develop chitosan-coated PLGA nanoparticles intended for nose-to-brain delivery of carmustine. Formulations were prepared by the double emulsion solvent evaporation method and optimized by using Box-Behnken Design. The optimized nanoparticles were obtained to satisfactory levels in terms of particle size, PDI, entrapment efficiency, and drug loading. In vitro drug release and ex-vivo permeation showed sustained release and enhanced permeability (approx. 2 fold) of carmustine compared to drug suspension. The AUC0-t of brain obtained with carmustine-loaded nanoparticles via nasal administration in Albino Wistar rats was 2.8 and 14.7 times that of intranasal carmustine suspension and intravenous carmustine, respectively. The MTT assay on U87 MG cell line showed a significant decrease (P < 0.05) in the IC50 value of the formulation (71.23 µg ml-1) as compared to drug suspension (90.02 µg ml-1).These findings suggest chitosan coated nanoparticles could be used to deliver carmustine via intranasal administration to treat Glioblastoma multiforme.

Asunto(s)

Quitosano , Glioblastoma , Nanopartículas , Animales , Ratas , Administración Intranasal , Quitosano/metabolismo , Carmustina/metabolismo , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Portadores de Fármacos/metabolismo , Encéfalo/metabolismo , Tamaño de la Partícula , Ratas Wistar , Sistemas de Liberación de Medicamentos/métodos

RESUMEN

Growing antibiotic resistance has become a major health problem and has encouraged many researchers to find an alternative class of antibiotics. Combination therapy (covalent/noncovalent) is supposed to increase antibacterial activity leading to a decrease in administration dosage, thus lowering the risk of adverse side effects. The covalent coupling sometimes leads to instability and loss in the structure of AMPs. Therefore, herein, we have reported innovative research involving the noncovalent coupling of melittin (MEL), an antimicrobial peptide with a series of synthesized less toxic pyrrolidinium-based ionic liquids (ILs) for which MTT assay was performed. The antibacterial results of conjugates showed remarkable improvement in the MIC value as compared to MEL and ILs alone against Escherichia coli and Staphylococcus aureus . In addition, hemocompatibility results suggested good selectivity of the noncovalent conjugate as a potential antibiotic agent. Further, the docking study was employed to acquire the most favorable conformation of MEL in the presence of ILs. The best possible complex was further studied using various spectroscopic techniques, which showed appreciable binding and stability of the complex.