Macrophage-Specific Targeting of Isoniazid Through Mannosylated Gelatin Microspheres

Abstract

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.

Inhaled microparticles of antitubercular antibiotic for in vitro and in vivo alveolar macrophage targeting and activation of phagocytosis

“…So, it may be anticipated that AM targeting through pulmonary administration of INH may improve patient compliance through reduction in dose, hepatotoxicity and shortening of treatment period. INH can be delivered through pulmonary route either as polymeric or nonpolymeric micro/nano particles 8,9 or pro-liposome formulation. 10 Spray drying is one of the most preferred techniques for development of particles for nasal and pulmonary delivery.…”

SLNs Based on Co-Processed Lipids for Topical Delivery of Terbinafine Hydrochloride

“…Particles were analyzed at an operation voltage of 5.00 kV [32]. As can be evidenced from SEM image (Figure 4), SLNs were of spherical shape with a regular surface profile.…”

Carbohydrate drugs: current status and development prospect

“…For example, lactosylated microspheres with high specificity for the asialoglycoprotein lectin expressed on mammalian hepatocytes have been created for liver-specific delivery of drugs and genes (58,59). Mannose modified liposomes selectively targeting their mannose receptors have also been developed as efficient alveolar macrophage selective drug carriers (60,61). Moreover, a novel lectindirected enzyme-activated prodrug therapy (LEAPT) has been developed for regio-selective drug release by carbohydrate-lectin interaction mediated localization of a glycosidase enzyme to the target cells (62).…”