Design and evaluation of polymer coated carvedilol loaded solid lipid nanoparticles to improve the oral bioavailability: A novel strategy to avoid intraduodenal administration

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2012-06, Vol.95, p.1-9
• Main Authors: Venishetty, Vinay Kumar, Chede, Raghavendra, Komuravelli, Rojarani, Adepu, Laxminarayana, Sistla, Ramakrishna, Diwan, Prakash V.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Bioavailability; Biological Availability; Carbazoles - administration & dosage; Carbazoles - chemistry; Carbazoles - pharmacokinetics; Carvedilol; Chitosan; Chitosan - administration & dosage; Chitosan - chemical synthesis; Chitosan - chemistry; Coated Materials, Biocompatible - administration & dosage; Coated Materials, Biocompatible - chemistry; Coated Materials, Biocompatible - pharmacokinetics; Coating; coatings; colloids; crystal structure; Drug delivery systems; Drug Design; Drugs; Duodenum - metabolism; Entrapment efficiency; Injections, Intravenous; Lipids; Lipids - chemistry; Male; metabolism; monoacylglycerols; Mouth - metabolism; N-carboxymethyl chitosan; Nanoparticles; Nanoparticles - chemistry; oral administration; Organ Specificity; Particle Size; patients; polymers; Polymers - administration & dosage; Polymers - chemical synthesis; Polymers - chemistry; Powder Diffraction; Propanolamines - administration & dosage; Propanolamines - chemistry; Propanolamines - pharmacokinetics; Rats; Rats, Wistar; Solid lipid nanoparticles; spectroscopy; Stearylamine; Strategy; surfactants; X-radiation; zeta potential
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2012.01.001

[Display omitted] ► We designed MCC-coated carvedilol loaded SLN to protect SLN from gastric milieu. ► Improved bioavailability with MCC coated-SLN (oral) compared to uncoated SLN (oral). ► No difference in bioavailability between MCC-SLN (oral) and uncoated SLN (duodenal). ► Clinically inappropriate duodenal administration can be avoided with MCC-SLN (oral). Solid lipid nanoparticles are most promising delivery systems for the enhancement of bioavailability of highly lipophilic drugs those prone to the first pass metabolism. But burst release of drug from solid lipid nanoparticles in acidic environment such as gastric milieu precludes its usage as oral delivery system. Studies on SLN revealed intraduodenal administration as an alternative route for SLN administration. But clinically it is an inappropriate route for repeated administration of drugs to patients. Hence, we prepared N-carboxymethyl chitosan (MCC) coated carvedilol loaded SLN to protect the rapid release of carvedilol in acidic environment. Positively charged carvedilol loaded SLN were developed using monoglyceride as lipid and soya lecithin and poloxamer 188 as surfactants and stearylamine as charge modifier. These SLN were characterized for particle size, zeta potential, entrapment efficiency, crystallinity and stability studies. Further these SLN were coated with N-carboxymethyl chitosan and confirmed by change in zetapotential and X-ray Photon Spectroscopic analysis. Effect of polymer coating on drug release profiles were studied simulated gastric and intestinal fluids. Effect of polymer coating on oral bioavailability of carvedilol loaded SLN were studied in rats after oral administration. MCC coated SLN improved the bioavailability of carvedilol compared uncoated SLN after oral administration. Insignificant difference in bioavailability was observed compared to intraduodenal administration of SLN. Hence, MCC coated SLN is a novel strategy to avoid intrduodenal administration.