Nanoparticle-Mediated Dual Targeting: An Approach for Enhanced Baicalin Delivery to the Liver

Autor:	Rehab Nabil Shamma, Iman S. Ahmed, Hassan M. Rashed, Faten Farouk, Hend Fayez
Rok vydání:	2020
Předmět:	radiolabeling lcsh:RS1-441 Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Article lcsh:Pharmacy and materia medica Chitosan 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Zeta potential Solubility chitosan lactate baicalin Chemical modification lactobionic acid 021001 nanoscience & nanotechnology Lactobionic acid chemistry ionic gelation method liver targeting Drug delivery nanoparticles in vivo biodistribution study 0210 nano-technology Baicalin Nuclear chemistry
Zdroj:	Pharmaceutics Volume 12 Issue 2 Pharmaceutics, Vol 12, Iss 2, p 107 (2020)
ISSN:	1999-4923
Popis:	In this study, water-soluble chitosan lactate (CL) was reacted with lactobionic acid (LA), a disaccharide with remarkable affinity to hepatic asialoglycoprotein (ASGP) receptors, to form dual liver-targeting LA-modified-CL polymer for site-specific drug delivery to the liver. The synthesized polymer was used to encapsulate baicalin (BA), a promising bioactive flavonoid with pH-dependent solubility, into ultrahigh drug-loaded nanoparticles (NPs) via the ionic gelation method. The successful chemical conjugation of LA with CL was tested and the formulated drug-loaded LA-modified-CL-NPs were assessed in terms of particle size (PS), encapsulation efficiency (EE) and zeta potential (ZP) using full factorial design. The in vivo biodistribution and pharmacokinetics of the designed NPs were assessed using 99mTc-radiolabeled BA following oral administration to mice and results were compared to 99mTc-BA-loaded-LA-free-NPs and 99mTc-BA solution as controls. Results showed that the chemical modification of CL with LA was successfully achieved and the method of preparation of the optimized NPs was very efficient in encapsulating BA into nearly spherical particles with an extremely high EE exceeding 90%. The optimized BA-loaded-LA-modified-CL-NPs showed an average PS of 490 nm, EE of 93.7% and ZP of 48.1 mV. Oral administration of 99mTc-BA-loaded-LA-modified-CL-NPs showed a remarkable increase in BA delivery to the liver over 99mTc-BA-loaded-LA-free-CL-NPs and 99mTc-BA oral solution. The mean area under the curve (AUC0&ndash 24) estimates from liver data were determined to be 11-fold and 26-fold higher from 99mTc-BA-loaded-LA-modified-CL-NPs relative to 99mTc-BA-loaded-LA-free-CL-NPs and 99mTc-BA solution respectively. In conclusion, the outcome of this study highlights the great potential of using LA-modified-CL-NPs for the ultrahigh encapsulation of therapeutic molecules with pH-dependent/poor water-solubility and for targeting the liver.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ba1c276fae8a35b67df9edf2992bade8 https://pubmed.ncbi.nlm.nih.gov/32013203 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.