Preparation of Paclitaxel Polymer Micelles and Its Anti-oral Squamous Cell Carcinoma Effect

doi:10.13701/j.cnki.kqyxyj.2025.04.005

Abstract

Abstract: Objective: To improve the water solubility of paclitaxel(PTX) and passive targeting of tumor by designing amphiphilic PEG-octadecamine block copolymers to form polymer micelles and encapsulating with PTX, and to explore its anti-tumor activity. Methods: PEG-octadecylamine polymer micelles (PEG-ODA-PTX) were coated with PTX by thin-film dispersion method.The particle size, Zeta potential, encapsulation rate, transmission electron microscopy (TEM) images, and stability of the PEG-ODA-PTX were investigated. The anti-tumor effect and cytotoxicity were detected by cell uptake evaluation, CCK-8 assay, and live/dead cell staining method. CAL-27 cells were used to construct a nude mouse transplanted tumor model, and its anti-tumor effect and biosafety were tested. Results: The particle size and Zeta potential of PEG-ODA-PTX were (188.4±7.9) nm and (28.50±0.1) mV, respectively. The encapsulation rate of PTX was about (76.43±1.2)%. Spherical structure with uniform size was observed under TEM. PEG-ODA-PTX showed good stability in 24 h. PEG-ODA-C6 could be specifically internalized by CAL-27 cells. PEG-ODA-PTX significantly inhibited the proliferation of CAL-27 cells and induced cell apoptosis. Compared with the control group, PEG-ODA-PTX significantly reduced the tumor volume in nude mice (P<0.05) and the tumor suppression rate reached 72%. Hemolysis, cytotoxicity, and H&E staining experiments confirmed the biosafety of PEG-ODA-PTX. Conclusion: The polymer micelles PEG-ODA-PTX was successfully prepared and showed significant targeting towards oral squamous cancer cells, which had excellent anti-oral squamous cell carcinomaeffect at both cellular and overall animal levels.

Key words: PEG, octadecylamine, paclitaxel, polymer micelles, oral squamous cell carcinom

YANG Haonan, LIU Feng, MENG Jian, ZHOU Lin, DAI Yuwei, CHEN Yinyu. Preparation of Paclitaxel Polymer Micelles and Its Anti-oral Squamous Cell Carcinoma Effect[J]. Journal of Oral Science Research, 2025, 41(4): 293-300.

References

[1] Ekanayaka RP, Tilakaratne WM, Amaratunga EA. Impact of histopathological parameters in prognosis of oral squamous cell carcinoma [J]. Oral Dis, 2024.
[2] Lu Y, Zheng Z, Yuan Y,, et al. The emerging role of exosomes in oral squamous cell carcinoma [J]. Front Cell Dev Biol, 2021, 9:628103.
[3] Li R, Xiao L, Gong T, et al. Role of oral microbiome in oral oncogenesis, tumor progression, and metastasis [J]. Mol Oral Microbiol, 2023, 38(1):9-22.
[4] Petersen EF, Larsen BS, Nielsen RB, et al. Co-release of paclitaxel and encequidar from amorphous solid dispersions increase oral paclitaxel bioavailability in rats [J]. Int J Pharm, 2024, 654:123965.
[5] Mubeen I, Abbas G, Shah S, et al. Conjugated linoleic acid-carboxymethyl chitosan polymeric micelles to improve the solubility and oral bioavailabilityof paclitaxel [J]. Pharmaceutics, 2024, 16(3):342.
[6] Liu Y, Zhang Y, Yan Q, et al. Evaluation of microstructure, dissolution rate, and oral bioavailability of paclitaxel poloxamer 188 solid dispersion [J]. Drug Deliv Transl Res, 2024, 14(2):329-341.
[7] Risinger AL, Riffle SM, Lopus M, et al. The taccalonolides and paclitaxel cause distinct effects on microtubule dynamics and aster formation [J]. Mol Cancer, 2014, 13:41.
[8] Habibi N, Mauser A, Ko Y, et al. Protein nanoparticles: Uniting the power of proteins with engineering design approaches [J]. Adv Sci (Weinh), 2022, 9(8):e2104012.
[9] Ghosh B, Biswas S. Polymeric micelles in cancer therapy: State of the art [J]. J Control Release, 2021, 332:127-147.
[10] Lu X, Wu H, Liang Y, et al. Redox-responsive prodrug for improving oral bioavailability of paclitaxel through bile acid transporter-mediated pathway [J]. Int J Pharm, 2021, 600:120496.
[11] 史雄喜,李江,邝艳婷,等.聚合物胶束在纳米载药体系的应用研究进展[J].化学与生物工程,2024,41(5):19-24.
[12] Liu C, Liu W, Liu Y, et al. Versatile flexible micelles integrating mucosal penetration and intestinal targeting for effectively oral delivery of paclitaxel [J]. Acta Pharm Sin B, 2023, 13(8):3425-3443.
[13] Zheng YT, Oz Y, Gu YM, et al. Rational design of polymeric micelles for targeted therapeutic delivery [J]. Nano Today, 2024, 55:102147.
[14] Zhang Z, Sun H, Giannino J, et al. Biodegradable zwitterionic polymers as PEG alternatives for drug delivery [J]. J Polym Sci (2020), 2024, 62(10):2231-2250.
[15] Wang Z, Ye Q, Yu S, et al. Polyethylene glycol (PEG) based hydrogels for drug delivery in cancer therapy: A comprehensive review [J]. Adv Healthc Mater, 2023, 12(18):e2300105.
[16] 任云,吕钦敬,薛强,等.归芪合剂联合聚乙二醇化重组人粒细胞集落刺激因子预防乳腺癌新辅助化疗后骨髓抑制的有效性及安全性[J].中国药物应用与监测,2024,21(5):665-669.
[17] Sivaram AJ, Wardiana A, Alcantara S, et al. Controlling the biological fate of micellar nanoparticles: Balancing stealth and targeting [J]. ACS Nano, 2020, 14(10):13739-13753.
[18] 景莎莎,梁宇,门靖,等.微柱离心-HPLC法测定枸橼酸他莫昔芬脂质体包封率的方法研究[J].精细化工中间体,2024,54(5):84-88.
[19] Yang L, Li H, Luo A, et al. Macrophage membrane-camouflaged pH-sensitive nanoparticles for targeted therapy of oral squamous cell [J]. J Nanobiotechnology, 2024, 22(1):168.
[20] Chow LQM. Head and neck cancer [J]. N Engl J Med, 2020, 382(1):60-72.