title: Systematic Approach for the Formulation and Optimization of Solid Lipid Nanoparticles of Efavirenz by High Pressure Homogenization Using Design of Experiments for Brain Targeting and Enhanced Bioavailability.
abstract: The nonnucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections, are reported to have low bioavailability pertaining to high first-pass metabolism, high protein binding, and enzymatic metabolism. They also show low permeability across blood brain barrier. The CNS is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective of providing increased permeability and protection of drug due to biocompatible lipidic content and nanoscale size and thus developing formulation having potential for enhanced bioavailability and brain targeting. Solid lipid nanoparticles were prepared by high pressure homogenization technique using a systematic approach of design of experiments (DoE) and evaluated for particle size, polydispersity index, zeta potential, and entrapment efficiency. Particles of average size 108.5 nm having PDI of 0.172 with 64.9% entrapment efficiency were produced. Zeta potential was found to be -21.2 mV and the formulation was found stable. Thein-vivopharmacokinetic studies revealed increased concentration of the drug in brain, as desired, when administered through intranasal route indicating its potential for an attempt towards complete eradication of HIV and cure of HIV-infected patients.
authors.affiliation: Department of Pharmaceutical Technology, Parul University, Vadodara, Gujarat, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Pharmaceutics, Oxbridge College of Pharmacy, Bangalore, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kesarla
authors.affiliation: Department of Pharmaceutics, A. R. College of Pharmacy, Vallabh Vidyanagar, Anand, Gujarat, India.
authors.forename: Narendra
authors.initials: N
authors.lastname: Chotai
authors.affiliation: Pharmacy Department, Faculty of Technology and Engineering, M. S. University of Baroda, Gujarat, India.
authors.forename: Ambikanandan
authors.initials: A
authors.lastname: Misra
authors.affiliation: Department of Chemistry & Biochemistry, Laurentian University, Greater Sudbury, ON, Canada.
authors.forename: Abdelwahab
authors.identifier: 0000-0002-4093-5762
authors.initials: A
authors.lastname: Omri
mesh_terms: D000480:Alkynes; D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology*; D001682:Biological Availability; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003521:Cyclopropanes; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D005079:Excipients; D006041:Goats; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009297:Nasal Mucosa / Q000187:drug effects / Q000473:pathology; D010316:Particle Size; D011312:Pressure; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D005079:Excipients; D008055:Lipids; D013501:Surface-Active Agents; C098320:efavirenz