title: Lipid Nanocarrier-Mediated Drug Delivery System to Enhance the Oral Bioavailability of Rifabutin.
abstract: Rifabutin (RFB) is prescribed for the treatment of tuberculosis infections as well as Mycobacterium avium complex (MAC) infection in immunocompromised individuals and HIV patients. With a view to develop a sustained release oral solid lipid nanoformulation (SLN), RFB was encapsulated in glyceryl monostearate (GMS) nanoparticles. The rifabutin solid lipid nanoparticles (RFB-SLNs), prepared by the solvent diffusion evaporation method, had a size of 345 ± 17.96 nm and PDI of 0.321 ± 0.09. The stability of RFB-SLNs was investigated in simulated gastric fluid (SGF) pH 2.0, simulated intestinal fluid (SIF) pH 6.8 and physiological buffer (PBS) pH 7.4. The gastric medium did not affect the SLNs and were found to be stable, while a sustained release was observed in SIF up to 48 h and in PBS up to 7 days. The pharmacokinetic profile of a single oral administration of RFB-SLNs in mice showed maintenance of therapeutic drug concentrations in plasma for 4 days and in the tissues (lungs, liver and spleen) for 7 days. Oral administration of free RFB showed clearance from plasma within 24 h. The relative bioavailability of RFB from SLNs was five fold higher as compared to administration with free RFB. The intent of using lipid nanocarriers is primarily to enhance the oral bioavailability of rifabutin and eventually decrease the dose and dosing frequency for successful management of MAC infection.
authors.affiliation: Lifecare Innovations Pvt Ltd, Laboratory for Translational Research in Nanomedicine, Biotech Park, Janakipuram, Lucknow, 226021, India.
authors.forename: Pradip
authors.initials: P
authors.lastname: Nirbhavane
authors.affiliation: Lifecare Innovations Pvt Ltd, Laboratory for Translational Research in Nanomedicine, Biotech Park, Janakipuram, Lucknow, 226021, India. nalinivemuri@lifecareinnovations.com.
authors.forename: Nalini
authors.initials: N
authors.lastname: Vemuri
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, 160062, India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Lifecare Innovations Pvt Ltd, Laboratory for Translational Research in Nanomedicine, Biotech Park, Janakipuram, Lucknow, 226021, India.
authors.forename: Gopal Krishan
authors.initials: GK
authors.lastname: Khuller
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D008055:Lipids / Q000737:chemistry*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D017828:Rifabutin / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D004337:Drug Carriers; D008055:Lipids; D017828:Rifabutin
keywords: coumarin-6; glyceryl monostearate; mycobacterium avium complex; rifabutin; solid lipid nanoparticles