NDLI: Solidified Self-Nanoemulsifying Formulation for Oral Delivery of Combinatorial Therapeutic Regimen: Part II In vivo Pharmacokinetics, Antitumor Efficacy and Hepatotoxicity

Content Provider	Springer Nature Link
Author	Jain, Amit K. Thanki, Kaushik Jain, Sanyog
Copyright Year	2013
Abstract	The present work focuses on the in vivo evaluation of tamoxifen and quercetin combination loaded into solid self-nanoemulsifying drug delivery system (s-Tmx-QT-SNEDDS).Lyophilization was employed to prepare s-Tmx-QT-SNEDDS using Aerosil 200 as carrier. The developed formulation was evaluated for in vitro cell cytotoxicity, in vivo pharmacokinetics, antitumor efficacy and toxicity studies. In vivo pharmacokinetics revealed ~8-fold and ~4-fold increase in oral bioavailability of tamoxifen and quercetin, respectively as compared to free counterparts. s-Tmx-QT-SNEDDS exhibited significantly higher cell cytotoxicity, as compared to free drug combination revealing ~32-fold and ~22-fold higher dose reduction index for tamoxifen and quercetin, respectively estimated using median effect dose analysis. s-Tmx-QT-SNEDDS could suppress tumor growth in DMBA induced tumor bearing animals by ~80% in contrast to ~35% observed with tamoxifen citrate. The significant appreciation in antitumor efficacy was further supported by normalized levels of tumor angiogenesis markers (MMP-2 and MMP-9). Finally, complete obliteration in tamoxifen induced hepatotoxicity was observed upon administration of developed formulation in contrast to that of clinically available tamoxifen citrate when measured as function of hepatotoxicity markers and histopathological changes.In nutshell, co-encapsulation of quercetin with tamoxifen in solid SNEDDS poses great potential in improving the therapeutic efficacy and safety of tamoxifen.
Starting Page	946
Ending Page	958
Page Count	13
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	31
Issue Number	4
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2013-10-18
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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