<p>Functionalization of nanoparticles enhances surface properties and characteristics, which can be explored for active targeting and developing a multifunctional carrier system for the cell-specific transport of therapeutic molecules. Development of nanotechnology provides opportunities to attach both therapeutic molecules and affinity moieties (mostly antibodies) with polymeric nanoparticles to create a multifunctional carrier assembly. In this work, a prototype polymeric nanocarriers (PNCs) (~ 100&#xa0;nm) was functionalized through the attachment of the antitubercular drug molecule isoniazid. Size of the functionalized PNCs was determined using Dynamic light scattering (DLS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Adsorption of isoniazid on the surface of PNCs was investigated using isotherm models. It was found that isoniazid had an 85.86% association efficiency with PNCs and INH released from the surface of PNCs is best fitted with the Higuchi model at pH 5.5 and the First-order kinetic model at pH 7.5. Antibacterial efficacy study against <i>Mycobacterium smegmatis</i> and <i>Escherichia coli</i> had shown the enhanced efficacy of isoniazid functionalized PNCs compared to the free isoniazid. Furthermore, a liquid inoculation assay demonstrated a significant reduction in colony-forming units (CFUs) using isoniazid functionalized PNCs. Surface functionalized PNC was attached with anti-intercellular adhesion molecule-1 (ICAM-1) antibody to enhance cell (A549 lung epithelial cells) specific targeting. The findings suggest that PNCs targeting ICAM-1 represent a viable platform by enhancing the uptake index ~ fivefold compared to the non-targeted PNCs. Consequently, polymeric nanocarriers may be advantageous for the delivery of anti-tubercular therapeutics and could improve the therapeutic strategy for tuberculosis treatment.</p>

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Functionalization of Polymeric Nanocarriers with Anti-tubercular Drug (isoniazid) for Cell-specific Targeting

  • Bhabatush Biswas,
  • Tarun Kanti Bandyopadhyay,
  • Tridib Kumar Bhowmick

摘要

Functionalization of nanoparticles enhances surface properties and characteristics, which can be explored for active targeting and developing a multifunctional carrier system for the cell-specific transport of therapeutic molecules. Development of nanotechnology provides opportunities to attach both therapeutic molecules and affinity moieties (mostly antibodies) with polymeric nanoparticles to create a multifunctional carrier assembly. In this work, a prototype polymeric nanocarriers (PNCs) (~ 100 nm) was functionalized through the attachment of the antitubercular drug molecule isoniazid. Size of the functionalized PNCs was determined using Dynamic light scattering (DLS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Adsorption of isoniazid on the surface of PNCs was investigated using isotherm models. It was found that isoniazid had an 85.86% association efficiency with PNCs and INH released from the surface of PNCs is best fitted with the Higuchi model at pH 5.5 and the First-order kinetic model at pH 7.5. Antibacterial efficacy study against Mycobacterium smegmatis and Escherichia coli had shown the enhanced efficacy of isoniazid functionalized PNCs compared to the free isoniazid. Furthermore, a liquid inoculation assay demonstrated a significant reduction in colony-forming units (CFUs) using isoniazid functionalized PNCs. Surface functionalized PNC was attached with anti-intercellular adhesion molecule-1 (ICAM-1) antibody to enhance cell (A549 lung epithelial cells) specific targeting. The findings suggest that PNCs targeting ICAM-1 represent a viable platform by enhancing the uptake index ~ fivefold compared to the non-targeted PNCs. Consequently, polymeric nanocarriers may be advantageous for the delivery of anti-tubercular therapeutics and could improve the therapeutic strategy for tuberculosis treatment.