Promises of a biocompatible nanocarrier in improved brain delivery of quercetin: Biochemical, pharmacokinetic and biodistribution evidences

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• 作者：Pramod Kumar^a ; Gajanand Sharma^b ; Rajendra Kumar^c ; Bhupinder Singh^b ; ^c ; Ruchi Malik^a ; Om Prakash Katare^b ; Kaisar Raza^a ; ^{drkaisar@curaj.ac.in} ; ^{razakaisar_pharma@yahoo.co.in}
• 关键词：Neuroprotection ; Neurological disorders ; Bioavailability ; Nanoparticles ; SLNs ; NLCs
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：30 December 2016
• 年：2016
• 卷：515
• 期：1-2
• 页码：307-314
• 全文大小：1265 K
• 卷排序：515

文摘

In various neurological disorders, antioxidants are frequently prescribed along with the specific treatment modalities. One such promising natural flavonoid is quercetin, offering better outcomes than established vitamins E and C. Though with immense promises, various challenges like poor oral-bioavailability (<2%), extensive first-pass metabolism, poor brain permeability, hydrophobic nature and physiological pH instability hinder its proper usage. Hence, it was planned to prepare quercetin-loaded nano lipidic carriers (NLCs) employing biocompatible components like phospholipids and tocopherol acetate for enhanced brain delivery. The outcomes were also compared with solid lipid nanoparticles (SLNs) of comparable composition. Both the nanocolloids offered better drug loading and controlled drug release with appreciable stability. In vitro antioxidant performance was improved after encapsulation in nanoparticles and the nanoparticles were substantially uptaken by Caco-2 cells. The difference in outcomes was vivid in pharmacokinetic studies, where nanoparticles, esp. NLCs substantially enhanced the relative bioavailability (approx. 6 folds), biological residence (2.5 times) and appreciably retarded the drug clearance (approx. 6 folds). On the other hand, both nanoparticles were able to substantially deliver the drug to brain. NLCs were observed to enhance the brain permeability of drug in a noticeable manner. In Conclusion, SLNs/NLCs can offer a better-platform for brain-delivery of quercetin.