| Autor: |
Ahalwat S; School of Medical and Allied Sciences, G. D. Goenka University, Gurugram 122103, India., Bhatt DC; Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar 125001, India., Rohilla S; Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar 125001, India., Jogpal V; School of Medical and Allied Sciences, G. D. Goenka University, Gurugram 122103, India., Sharma K; School of Medical and Allied Sciences, G. D. Goenka University, Gurugram 122103, India., Virmani T; School of Pharmaceutical Sciences, MVN University, Palwal 121105, India., Kumar G; School of Pharmaceutical Sciences, MVN University, Palwal 121105, India., Alhalmi A; Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India., Alqahtani AS; Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia., Noman OM; Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia., Almoiliqy M; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. |
| Abstrakt: |
Resistance to isoniazid (INH) is common and increases the possibility of acquiring multidrug-resistant tuberculosis. For this study, isoniazid-loaded nanostructured lipid carriers (INH-NLCs) were developed and effectively functionalized with mannose (Man) to enhance the residence time of the drug within the lungs via specific delivery and increase the therapeutic efficacy of the formulation. The mannose-functionalized isoniazid-loaded nanostructured lipid carrier (Man-INH-NLC) formulation was evaluated with respect to various formulation parameters, namely, encapsulation efficiency (EE), drug loading (DL), average particle size (PS), zeta potential (ZP), polydispersity index (PDI), in vitro drug release (DR), and release kinetics. The in vitro inhalation behavior of the developed formulation after nebulization was investigated using an Andersen cascade impactor via the estimation of the mass median aerosolized diameter (MMAD) and geometric aerodynamic diameter (GAD) and subsequently found to be suitable for effective lung delivery. An in vivo pharmacokinetic study was carried out in a guinea pig animal model, and it was demonstrated that Man-INH-NLC has a longer residence time in the lungs with improved pharmacokinetics when compared with unfunctionalized INH-NLC, indicating the enhanced therapeutic efficacy of the Man-INH-NLC formulation. Histopathological analysis led us to determine that the extent of tissue damage was more severe in the case of the pure drug solution of isoniazid compared to the Man-INH-NLC formulation after nebulization. Thus, the nebulization of Man-INH-NLC was found to be safe, forming a sound basis for enhancing the therapeutic efficacy of the drug for improved management in the treatment of pulmonary tuberculosis. |
