Macrophage-Specific Targeting of Isoniazid Through Mannosylated Gelatin Microspheres |
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Authors: | Sanjay Tiwari Adya P Chaturvedi Yamini B Tripathi Brahmeshwar Mishra |
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Institution: | (1) Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi, (U.P.), 221005, India;(2) Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, (U.P.), 221005, India; |
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Abstract: | Active targeting of drug molecules can be achieved by effective attachment of suitable ligands to the surface of carriers.
The present work was attempted to prepare mannosylated gelatin microspheres (m-GMs) so as to achieve targeted delivery of
isoniazid (INH) to alveolar macrophages (AMs) and maintain its therapeutic concentration for prolonged period of time. Microspheres
were prepared by emulsification solvent extraction method and evaluated for physicochemical characteristics, drug release,
ex vivo drug uptake by AMs and pharmacokinetic characteristics. Fourier transform infrared spectroscopy and nuclear magnetic resonance
spectral analysis confirmed that mannosylation took place through Schiff base formation between aldehyde and amino groups
of mannose and gelatin, respectively. Prepared microspheres offered suitable physicochemical characteristics for their delivery
to AMs. Their average size was about 4 μm and drug entrapment efficiency of 56% was achieved with them. Ex vivo uptake results indicated that in comparison to plain microspheres, m-GMs were selectively uptaken and were found to be associated
with phago-lysosomal vesicles of AMs. Pharmacokinetic studies showed the formulation could maintain the therapeutic concentration
of INH for prolonged period of time even with a reduced clinical dose. m-GMs were found to be stable in broncheo-alveolar
lavage fluid. The study concluded that ligand decorated carriers could be a potential strategy to improve the therapeutic
properties of INH. |
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