Stealth Nanoparticle Formulation of Rifampicin Using PEGylated Chitosan for Enhanced Pulmonary Retention and Reduced Systemic Toxicity

Background:The treatment of tuberculosis (TB) necessitates continuous and frequent administration of multiple pharmacological agents, posing significant challenges related to patient adherence as a primary disadvantage.Objectives: The current research endeavor was directed towards the formulation and evaluation of Rifampicin (RIF) stealth nanoparticles designed to enhance circulation duration (Stealth) while mitigating systemic toxicity.Methods: The ionic gelation technique was employed to fabricate nanoparticles using specifically engineered carriers, including chitosan (CS) and polyethylene glycol (PEG) with molecular weights of 4000, 6000, and 9000, for the encapsulation of RIF.The synthesized nanoparticles underwent comprehensive characterization, including Fourier-transform infrared spectroscopy (FT-IR) to assess drug-polymer compatibility, scanning electron microscopy (SEM) for surface morphology and particle size analysis, zeta potential measurements to determine surface charge, as well as evaluations of drug content, in vitro release profiles, stability assessments, and drug deposition studies.Results: The physicochemical properties and surface characteristics of the chitosan-rifampicin (CS-RIF) stealth nanoparticles exhibited alterations post-PEG incorporation, resulting in increased particle size and enhanced drug encapsulation efficiency.Notably, the PEG-coated CS-RIF nanoparticles demonstrated significantly prolonged retention in circulation when juxtaposed with unmodified RIF powder.Fouriertransform infrared spectroscopy analyses corroborated the absence of any interaction between the drug and the polymer matrix.Particle size characterization indicated that the optimized RIF stealth nanoparticles exhibited dimensions ranging from 58.75 to 493.4 nm, with entrapment efficiencies recorded between 70.5 and 90.71%.The cumulative percentage of in vitro drug release was observed to lie between 65.81 and 85.17% over 12 hours.The release kinetics adhered to a non-Fickian diffusion mechanism across all experimental batches, and stability studies confirmed the robustness of the formulated nanoparticles.In vivo drug deposition investigations conducted on Wistar albino rats revealed a significantly reduced accumulation in hepatic and renal tissues relative to the free drug, attributable to the PEG coating. Conclusion:The overarching objective of this study, which is to diminish toxicity while augmenting the retention time of the drug within the biological system, can be effectively realized through the application of CS-RIF stealth nanoparticles.