title: Lipid nanoparticles for oral delivery of raloxifene: optimization, stability, in vivo evaluation and uptake mechanism.
abstract: Raloxifene HCl (RLX) shows low oral bioavailability (<2%) in humans due to poor aqueous solubility and extensive (>90%) metabolism in gut. Lipid nanoparticles (SLN) with glyceryl tribehenate were designed to enhance drug's oral bioavailability. Box-Bhenken design was used to optimize manufacturing conditions. Optimized SLN had particle size of 167±3nm and high encapsulation efficiency (>92%). Oral bioavailability of RLX from SLN was improved by 3.24 folds compared to free RLX in female Wistar rats. Both clathrin and caveolae mediated endocytosis pathways were involved in the uptake of SLN. Lymphatic transport inhibitor, cycloheximide significantly reduced oral bioavailability of SLN.
authors.affiliation: Department of Pharmacy, BITS-Pilani Hyderabad Campus, Jawaharnagar, Ranga Reddy (Dist.), Andhra Pradesh, India. Electronic address: rpunnarao@hyderabad.bits-pilani.ac.in.
authors.forename: Punna Rao
authors.initials: PR
authors.lastname: Ravi
authors.affiliation: Department of Pharmacy, BITS-Pilani Hyderabad Campus, Jawaharnagar, Ranga Reddy (Dist.), Andhra Pradesh, India. Electronic address: aditya@hyderabad.bits-pilani.ac.in.
authors.forename: N
authors.initials: N
authors.lastname: Aditya
authors.affiliation: Department of Pharmacy, BITS-Pilani Hyderabad Campus, Jawaharnagar, Ranga Reddy (Dist.), Andhra Pradesh, India. Electronic address: himanshukathuria001@gmail.com.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Kathuria
authors.affiliation: Department of Pharmacy, BITS-Pilani Hyderabad Campus, Jawaharnagar, Ranga Reddy (Dist.), Andhra Pradesh, India. Electronic address: malekarshrinivas@yahoo.com.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Malekar
authors.affiliation: Department of Pharmacy, BITS-Pilani Hyderabad Campus, Jawaharnagar, Ranga Reddy (Dist.), Andhra Pradesh, India. Electronic address: rahulvats@hyderabad.bits-pilani.ac.in.
authors.forename: Rahul
authors.initials: R
authors.lastname: Vats
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D005227:Fatty Acids / Q000737:chemistry*; D005260:Female; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017208:Rats, Wistar; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D005227:Fatty Acids; D020845:Selective Estrogen Receptor Modulators; D020442:Poloxamer; C086409:glyceryl behenate; D020849:Raloxifene Hydrochloride
keywords: Box–Bhenken design; Design of experiments; Everted gut sac; Glyceryl behenate; Lymphatic transport; Raloxifene HCl; Solid lipid nanoparticle