Mannosylated nanoparticulate carriers of rifabutin for alveolar targeting.
The objective of the present study was to evaluate the prospective of engineered nanoparticles for selective delivery of an antituberculosis drug, rifabutin, to alveolar tissues. Drug-loaded solid lipid nanoparticles (SLNs) were synthesized and efficiently mannosylated. The formation of uncoated and coated SLNs was characterized by FTIR spectroscopy and SEM studies. A variety of physicochemical parameters such as drug loading, particle size, polydispersity index, zeta potential, and in vitro drug release were determined. The toxicity and targeting potential of the prepared formulation were assessed with alveolar macrophage uptake, hematological studies, and in vivo studies of uncoated and coated SLNs. Ex vivo cellular uptake studies of SLNs formulations in alveolar macrophages depicted almost six times enhanced uptake due to mannose coating. The hematological studies proved mannose-conjugated system to be less immunogenic and suitable for sustained delivery as evaluated against uncoated formulation. Further, the serum level and organ distribution studies demonstrated efficiency of the system for prolonged circulation and spatial delivery of rifabutin to alveolar tissues. Finally, it was concluded that mannose-conjugated SLNs can be exploited for effective and targeted delivery of rifabutin compared to its uncoated formulation and ultimately increasing the therapeutic margin of safety while reducing the side effects.
Nimje
Navneet
N
Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar, India.
Agarwal
Abhinav
A
Saraogi
Gaurav Kant
GK
Lariya
Narendra
N
Rai
Gopal
G
Agrawal
Himanshu
H
Agrawal
G P
GP
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005260:Female; D008055:Lipids / Q000737:chemistry; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008358:Mannose / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D017828:Rifabutin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D017550:Spectroscopy, Fourier Transform Infrared; D014018:Tissue Distribution
D000904:Antibiotics, Antitubercular; D003692:Delayed-Action Preparations; D008055:Lipids; D017828:Rifabutin; D008358:Mannose