Development and evaluation of Chitosan nanoparticles based dry powder inhalation formulations of Prothionamide

Abstract

Prothionamide (PTH), a second line antitubercular drug is used to administer in conventional oral route. However, its unpredictable absorption and frequent administration limit its use. An alternate approach was thought of administering PTH through pulmonary route in a form of nanoparticles, which can sustain the release for several hours in lungs. Chitosan, a bio-degradable polymer was used to coat PTH and further freeze dried to prepare dry powder inhaler (DPI) with aerodynamic particle size of 1.76μm. In vitro release study showed initial burst release followed by sustained release up to 96.91% in 24h. In vitro release further correlated with in vivo study. Prepared DPI maintained the PTH concentration above MIC for more than 12h after single dose administration and increased the PTH residency in the lungs tissue more than 24h. Animal study also revealed the reduction of dose in pulmonary administration, which will improve the management of tuberculosis.

Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs

“…Chitosan NPs-loaded-killed SwIAV antigen (KAg) (CNPs-KAg) formulation was prepared by the ionic gelation method as described previously ( 23 , 30 – 32 ) with some modifications. Briefly, 1.0% (w/v) low-molecular weight chitosan polymeric (Sigma, MO, USA) solution was prepared in an aqueous solution of 4.0% acetic acid under magnetic stirring until the solution became clear.…”

Molecular Mechanisms of Chitosan Interactions with Fungi and Plants

“…This makes it suitable for clinical application. Nanotechnology allows new chitosan formulations (e.g., nanofibres, nanocomposites, or nanocapsules) with potential for drug delivery, in medical mycology and biotechnology [24,56,57,58,59,60,61]. These findings open-up new possibilities to develop chitosan as a natural antifungal compound for practical use.…”

Nanotechnology‐Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

“…Comparison of inhalation techniques: oropharyngeal aspiration and intratracheal instillation using Microsprayer Aerosolizer or BioLite Intubation System in Swiss Webster mice; oropharyngeal aspiration showed microsphere deposition in the oral cavity; intratracheal instillation techniques resulted in the most efficient deposition in the lungs [80] Chitosan NPs, lactose preblend BDQ Dry powder formulation; no cytotoxicity on J774 cells; no toxicity in Wistar rats, highest accumulation in lungs, least concentration in blood as compared to inhaled free BDQ or orally administered BDQ solution [81] Poly( -cyclodextrin) NPs ETH and its booster Coencapsulated formulation had improved activity against intracellular bacteria on RAW 267.4 cells infected with Mtb H37Rv; effective reduction of bacterial burden with subtherapeutic doses in BALB/c mice (intranasally infected with Mtb H37Rv) after intratracheal aerosol administration (Microsprayer) [82] Chitosan NPs, mixed with lactose Prothionamide (PTH) Better pharmacokinetic profile than free PTH; maintained drug concentration in lungs above MIC after administration of formulation with dry powder inhaler delivery device via intratracheal route in Wistar rats [83] Chitosan NPs, mixed with mannitol and leucine RIF, INH Coencapsulated dry powder formulation showed increased bioavailability for both drugs in lungs, and other macrophage-rich organs (spleen, kidney, liver); effective reduction of bacterial level after pulmonary administration with a compressor nebulizer system in BALB/c mice (infected with Mtb H37Rv through aerosol route) [84] BSA-based nano-and microparticles…”