Role of Nanostructured Lipid Carriers for the Management of Pulmonary Tuberculosis
Varsha R. Jadhav
College of Pharmacy and Research Centre, Phaltan, Satara, 415523, India.
Gouri Ithape
Gourishankar Institute of Pharmaceutical Education and Research, Limb, Satara, India.
Prajakta Kamble
Gourishankar Institute of Pharmaceutical Education and Research, Limb, Satara, India.
Nutan Kamble
Gourishankar Institute of Pharmaceutical Education and Research, Limb, Satara, India.
Gauri Patki
Jawaharlal Nehru Technological University, Hyderabad, Telangana, India.
Vipul Sansare *
Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400098, India.
Deepa Warrier
Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400098, India.
Ujwala Shinde
Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400098, India.
*Author to whom correspondence should be addressed.
Abstract
Tuberculosis continues to be a major global health concern, particularly in developing and underdeveloped countries. Infected alveolar macrophages are known to overexpress specific receptors that can be selectively exploited for targeted drug delivery. The present study aimed to develop mannose-anchored rifampicin-loaded nanostructured lipid carriers (NLCs) for active targeting of alveolar macrophages in tuberculosis therapy. The targeting ligand, N-octadecyl-mannopyranosylamine, was synthesised and characterised prior to formulation. Rifampicin-loaded NLCs were prepared using the melt homogenization–ultrasonication technique, employing stearic acid and oleic acid as lipid components. Particle size and zeta potential were determined by photon correlation spectroscopy (Zetasizer Nano ZS, Malvern Instruments, UK) at 25 °C, with appropriate dilution to avoid inter-particle scattering.
The mannose-decorated rifampicin NLCs were comprehensively characterised for their physicochemical properties, drug loading, physical state of components, in vitro drug release, and in vitro lung deposition. Antimicrobial efficacy was assessed against Bacillus subtilis. Furthermore, cytotoxicity and cellular internalisation studies were conducted on RAW 264.7 alveolar macrophage cell lines using confocal laser scanning microscopy. The developed NLCs demonstrated favourable aerodynamic properties, sustained drug release behaviour, and preserved antimicrobial activity. Cell viability studies confirmed the non-cytotoxic nature of the nanocarriers. Mannose-anchored NLCs exhibited significantly enhanced cellular internalisation compared to non-conjugated formulations, confirming effective macrophage targeting.
The spray-dried NLCs formed spherical, micron-sized particles suitable for pulmonary delivery via a dry powder inhaler. Upon dispersion in aqueous media, efficient reconstitution and release of nanoparticles were observed. Overall, the developed rifampicin-loaded, mannose-anchored NLC-based dry powder inhalation system shows strong potential as a targeted pulmonary therapy for tuberculosis.
Keywords: Tuberculosis, rifampicin, NLCs