Dataset Information

Preparation of a camptothecin analog FLQY2 self-micelle solid dispersion with improved solubility and bioavailability.

ABSTRACT:

Background

7-p-trifluoromethylphenyl-FL118 (FLQY2) is a camptothecin analog with excellent antitumor efficacy against various solid tumors. However, its poor solubility and low bioavailability limited the development of the drug. Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus^®), an emerging carrier for preparing solid dispersion (SD), encapsulated FLQY2 to circumvent the above limitations.

Results

In this project, FLQY2-SD was prepared by solvent evaporation method and self-assembled into micelles in aqueous solutions owing to the amphiphilic nature of Soluplus^®. The physicochemical characterizations demonstrated that FLQY2 existed in a homogeneous amorphous form in SD and was rapidly dissolved. The micelles did not affect cytotoxicity or cellular uptake of FLQY2 in vitro, and the oral bioavailability was increased by 12.3-fold compared to the FLQY2 cyclodextrin suspension. The pharmacokinetics of FLQY2-SD showed rapid absorption, accumulation in the intestine, and slow elimination via fecal. Metabolite identification studies showed 14 novel metabolites were identified, including 12 phase I metabolites (M1-M12) and 2 phase II metabolites (M13-M14), of which M2 (oxidation after decarboxylation) and M7 (dioxolane ring cleavage) were the primary metabolites in the positive mode and negative mode, respectively. The tumor growth inhibition rate (TGI, 81.1%) of FLQY2-SD (1.5 mpk, p.o./QW) in tumor-bearing mice after oral administration was higher than that of albumin-bound Paclitaxel (15 mpk, i.v./Q4D) and Irinotecan hydrochloride (100 mpk, i.p./QW).

Conclusions

The successful preparation, pharmacokinetics, and pharmacodynamics studies of FLQY2-SD showed that the solubility and bioavailability of FLQY2 were improved, which facilitated the further druggability development of FLQY2.

SUBMITTER: Wang Y

PROVIDER: S-EPMC9446799 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Preparation of a camptothecin analog FLQY2 self-micelle solid dispersion with improved solubility and bioavailability.

Wang Yi Y Wang Wenchao W Yu Endian E Zhuang Wenya W Sun Xuanrong X Wang Hong H Li Qingyong Q

Journal of nanobiotechnology 20220905 1

<h4>Background</h4>7-p-trifluoromethylphenyl-FL118 (FLQY2) is a camptothecin analog with excellent antitumor efficacy against various solid tumors. However, its poor solubility and low bioavailability limited the development of the drug. Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus<sup>®</sup>), an emerging carrier for preparing solid dispersion (SD), encapsulated FLQY2 to circumvent the above limitations.<h4>Results</h4>In this project, FLQY2-SD was prep ...[more]

PMID: 36064403

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Dataset Information

Preparation of a camptothecin analog FLQY2 self-micelle solid dispersion with improved solubility and bioavailability.

Background

Results

Conclusions

Publications

Preparation of a camptothecin analog FLQY2 self-micelle solid dispersion with improved solubility and bioavailability.

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