title: Lipomer of doxorubicin hydrochloride for enhanced oral bioavailability.
abstract: The present study discusses design of doxorubicin hydrochloride (Dox) loaded lipid based nanocarrier (LIPOMER) for oral delivery. High entrapment (>90 %) and high loading (38.11 ± 0.37 %w/w) of hydrophilic Dox in lipid nanocarrier of polyglyceryl-6-distearate was achieved using poly(methyl vinyl ether-co-maleic anhydride) (Gantrez AN 119) and a modified nanoprecipitation method. Dox-LIPOMER revealed nanosize (314 ± 16.80 nm) and negative zeta potential (-25.00 ± 2.41 mV). Dox-LIPOMER exhibits sustained release in vitro and was influenced by ionic strength of dissolution medium. DSC and XRD studies suggested amorphous nature of Dox in LIPOMER. TEM revealed spherical morphology of Dox-LIPOMER. Dox-LIPOMER was stable up to 12 months at 25 °C/60 % RH. A 384 % enhancement in oral bioavailability compared to Dox solution was observed following Dox-LIPOMER administration at 10 mg/kg body weight. Superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) assay data of heart and kidney tissues of rats treated with Dox-LIPOMER were comparable with untreated rats. Dox-LIPOMER represents a potential safe drug delivery system for oral administration.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N P Marg, Matunga (E), Mumbai 400019, India.
authors.forename: Derajram M
authors.initials: DM
authors.lastname: Benival
authors.forename: Padma V
authors.initials: PV
authors.lastname: Devarajan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002374:Catalase / Q000378:metabolism; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005260:Female; D005990:Glycerol / Q000031:analogs & derivatives* / Q000737:chemistry; D006321:Heart / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008298:Maleates / Q000737:chemistry*; D008315:Malondialdehyde / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009206:Myocardium / Q000378:metabolism; D053758:Nanoparticles; D036103:Nanotechnology; D009994:Osmolar Concentration; D018384:Oxidative Stress / Q000187:drug effects; D011108:Polymers / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D033362:Powder Diffraction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013482:Superoxide Dismutase / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008055:Lipids; D008298:Maleates; D011108:Polymers; D011145:Polyvinyls; C558490:polyglycerol 6-distearate; C058026:polyvinylmethoxyethylene-maleic anhydride copolymer; D008315:Malondialdehyde; D004317:Doxorubicin; D002374:Catalase; D013482:Superoxide Dismutase; D005990:Glycerol