Browsing by Author "Sanjay Tiwari"

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Macrophage-specific targeting of isoniazid through mannosylated gelatin microspheres
(2011) Sanjay Tiwari; Adya P. Chaturvedi; Yamini B. Tripathi; Brahmeshwar Mishra
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. © 2011 American Association of Pharmaceutical Scientists.
Microspheres based on mannosylated lysine-co-sodium alginate for macrophage-specific delivery of isoniazid
(2012) Sanjay Tiwari; Adya Prasad Chaturvedi; Yamini Bhusan Tripathi; Brahmeshwar Mishra
The present investigation reports coupling of ε- and α-amino groups of lysine (LS) with mannose (m-LS) and sodium alginate (SA), respectively, to reduce its toxicity. Prepared conjugate, m-LS-co-SA, was characterized through infra-red spectroscopy and differential scanning calorimetry. Cell viability studies were undertaken to assess the safety profile of the prepared conjugate. Microspheres, based on the conjugate, were prepared using spray drying technique and studied for targeting of isoniazid to alveolar macrophages (AMs). Pharmacokinetic studies of the optimized formulation batch were performed in Charles Foster rats. Infra-red spectral data of the synthesized conjugate were in agreement to the presumptive sequence of the conjugation process. Dispersibility, thermal stability and safety of the conjugate were conducive to its biomedical application. Microspheres, formulated from the conjugate, were of uniform size and offered satisfactory drug loading efficiency and in vitro release characteristics. X-ray diffraction studies established that drug was entrapped within the microspheres rather than being adsorbed on to the surface. Pharmacokinetic studies revealed that the conjugate could be a potential vehicle towards both active targeting of isoniazid to AMs and controlling its release rate. © 2011 Elsevier Ltd. All rights reserved.