title: Rifampicin loaded chitosan nanoparticle dry powder presents an improved therapeutic approach for alveolar tuberculosis.
abstract: Current treatment therapeutic approach for tuberculosis is the administration of first line drugs in the form of tablets and capsules for 4-6 months. However, this approach leads to severe adverse effects. Therefore, present study was designed to achieving local and sustained targeting of anti-tubercular drugs in order to reduce dose and frequency. The nanoparticle based dry powder formulation of rifampicin was developed and analyzed with respect to its direct targeting potential of lungs. Rifampicin loaded nanoparticles were formulated by ionic gelation probe sonication method, and characterized with respect to particle size, zeta potential, entrapment and drug loading efficiency. The range of size and entrapment efficiency of prepared nanoparticles was estimated from 124.1±0.2 to 402.3±2.8nm and 72.00±0.1%, respectively. The freeze-dried powder of nanoparticle formulation was used to carry out in vitro lung deposition studies through Andersen cascade impactor. The cumulative in vitro drug release studies with developed nanoparticle formulation showed sustained release up to 24h. Our in vitro sustained drug release results were corroborated by the extended residence and slow clearance of rifampicin from the lungs. Furthermore, our results suggest the minimum lung distribution of drug in treated rats which confirms the negligible toxicity rendered by nanoparticle dry powder formulation. Moreover, pharmacokinetic and toxicity studies carried out with prepared NPs dry powder inhalation (DPI) formulations and compared with conventional DPI.
authors.affiliation: Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India.
authors.forename: Tejal
authors.initials: T
authors.lastname: Rawal
authors.affiliation: Institute of Science, Nirma University, Ahmedabad 382481, Gujarat, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Parmar
authors.affiliation: Institute of Science, Nirma University, Ahmedabad 382481, Gujarat, India.
authors.forename: Rajeev K
authors.initials: RK
authors.lastname: Tyagi
authors.affiliation: Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India. Electronic address: shital_26@yahoo.com.
authors.forename: Shital
authors.initials: S
authors.lastname: Butani
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D065546:Drug Liberation; D058995:Dry Powder Inhalers; D005612:Freeze Drying; D006207:Half-Life; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011208:Powders; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000737:chemistry / Q000493:pharmacokinetics*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D003692:Delayed-Action Preparations; D011208:Powders; D048271:Chitosan; D012293:Rifampin
keywords: Chitosan; Dry powder; Freeze drying; Nanoparticles; Pulmonary; Rifampicin