ScholarWorks@숙명여자대학교

초록

PurposeOvarian cancer (OC) is difficult to detect early; therefore, it is highly likely to advance to peritoneal metastasis at the time of diagnosis. Moreover, multi-drug resistance (MDR) results in a high recurrence rate. To address these issues, the present study aimed to design an intraperitoneally administered formulation combining a d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) micelles loaded with paclitaxel (PTX) and olaparib (OLA) and a pH-thermosensitive hydrogel.MethodsTo assess PTX and OLA's synergistic effects, we evaluated the combination index (CI) at various molar ratios and physicochemical properties of the formulations and carried out both in vitro and in vivo experiments.ResultsPTX and OLA showed a synergistic effect at all ratios, and considering the various physicochemical properties, a 1:4 ratio using 50 mg of TPGS and a gel polymer concentration of 12.5% w/v was identified as the optimum formulation. In vitro cytotoxicity and cellular uptake assays demonstrated high cytotoxicity of the TPGS micelles compared to those of the free drug and methoxy-poly(ethylene glycol)-poly(epsilon-caprolactone) (mPEG-PCL) micelles (control) in all formulation groups; TPGS micelles also increased cellular uptake efficiency. Drug release profiles in vitro demonstrated that both PTX and OLA had a release pattern influenced by pH levels, with the slowest release observed at pH 7.4. In vitro and in vivo drug release profiles showed similar release patterns, with PTX showing slower release than OLA.ConclusionThe final formulation of this study represents a promising therapeutic strategy for OC; however, due to potential toxicity issues of the polymer, its clinical application needs to be further studied.

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