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Abstract
Context: HIV-1 associated dementia (HAD) is an evolving disease in the category of neurological disorders.
Objective: Nifedipine-loaded solid lipid nanoparticles (SLNs) were developed and coated with Tween 80 to facilitate enhanced brain drug delivery for the treatment of HAD.
Materials and methods: SLNs were prepared using solvent injection method. Lipids consisted of tristearin, hydrogenated soya phosphatidylcholine (HSPC) (1.5:1 w/w). Nifedipine was model drug in this study. Tween 80 (0.5% v/v) was taken as key modulator. SLNs were characterized for particle shape, size, zeta potential, entrapment efficiency, in vitro drug release, DNA fragmentation, cytotoxicity potential and in vivo studies.
Results: The SLNs (plain and coated) were found to be in nanometric in size (∼120 nm) with more than 70% entrapment efficiency. In vitro drug release profile reflected sustained release up to 48 h. Tween 80-coated SLNs showed higher percentage of DNA fragmentation in vitro and enhanced cell viability in sulforhodamine assay (rat cortical cells) as compared to plain drug and uncoated SLNs due to facilitated uptake of SLNs and reversal of P-gp efflux by virtue of Tween 80. Biodistribution study performed on vital organs, i.e. brain, heart, liver, spleen, lungs and kidney showed increased accumulation of Tween 80-coated SLNs in the brain.
Discussion and conclusion: Tween 80 enhanced localization of SLNs in the brain as compared to uncoated SLNs. This approach can be employed effectively to transport chemotherapeutics across the BBB for management of HIV-1 associated dementia and other ailments.
Acknowledgements
We are highly thankful to Punjab University, Chandigarh providing the IR facility, Anatomy division of AIIMS, New Delhi for conducting TEM, National Institute of Pharmaceutical Education and Research (NIPER) Chandigarh for zeta potential, and Nanoscience department of IIT KANPUR for providing SEM facility. We would like to offer deepest thanks to Dr. A. K. Saxena and Miss Gousia Chashoo, IIIM Jammu, for providing the facility for ex-vivo study.
Declaration of interest
The authors declare no conflict of interest.
The authors acknowledge University Grant Commission (UGC, New Delhi) and Council of Scientific and Industrial Research (CSIR, New Delhi) for awarding Junior Research Fellowship and Senior Research Fellowship to Mr. Ankit Rai and Mr. Ankit Jain, respectively.