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author:

Wang, Ling (Wang, Ling.) [1] | Cai, Fangqing (Cai, Fangqing.) [2] | Li, Yixuan (Li, Yixuan.) [3] | Lin, Xiaolan (Lin, Xiaolan.) [4] | Wang, Yuting (Wang, Yuting.) [5] | Liang, Weijie (Liang, Weijie.) [6] | Liu, Caiyu (Liu, Caiyu.) [7] | Wang, Cunze (Wang, Cunze.) [8] | Ruan, Junshan (Ruan, Junshan.) [9]

Indexed by:

Scopus SCIE

Abstract:

Purpose: Renal cell carcinoma (RCC) is the most common and lethal type of urogenital cancer, with one-third of new cases presenting as metastatic RCC (mRCC), which, being the seventh most common cancer in men and the ninth in women, poses a significant challenge. For patients with poor prognosis, temsirolimus (TEM) has been approved for first-line therapy, possessing pharmacodynamic activities that block cancer cell growth and inhibit proliferation-associated proteins. However, TEM suffers from poor water solubility, low bioavailability, and systemic side effects. This study aims to develop a novel drug formulation for the treatment of RCC. Methods: In this study, amphiphilic block copolymer (poly(ethylene glycol) monomethyl ether-poly(beta-amino ester)) (mPEGPBAE) was utilized as a drug delivery vehicle and TEM-loaded micelles were prepared by thin-film hydration method by loading TEM inside the nanoparticles. Then, the molecular weight of mPEG-PBAE was controlled to make it realize hydrophobic-hydrophilic transition in the corresponding pH range thereby constructing pH-responsive TEM-loaded micelles. Characterization of pH-responsive TEM-loaded nanomicelles particle size, potential and micromorphology while its determination of drug-loading properties, in vitro release properties. Finally, pharmacodynamics and hepatorenal toxicity were further evaluated. Results: TEM loading in mPEG-PBAE increased the solubility of TEM in water from 2.6 mu g/mt to more than 5 mg/mt. The pH-responsive TEM-loaded nanomicelles were in the form of spheres or spheroidal shapes with an average particle size of 43.83 nm and a Zeta potential of 1.79 mV. The entrapment efficiency (EE) of pH-responsive TEM nanomicelles with 12.5% drug loading reached 95.27%. Under the environment of pH 6.7, the TEM was released rapidly within 12 h, and the release rate could reach 73.12% with significant pH-dependent characteristics. In vitro experiments showed that mPEG-PBAE preparation of TEM-loaded micelles had non-hemolytic properties and had significant inhibitory effects on cancer cells. In vivo experiments demonstrated that pH-responsive TEM-loaded micelles had excellent antitumor effects with significantly reduced liver and kidney toxicity. Conclusion: In conclusion, we successfully prepared pH-responsive TEM-loaded micelles. The results showed that pH-responsive TEM-loaded micelles can achieve passive tumor targeting of TEM, and take advantage of the acidic conditions in tumor tissues to achieve rapid drug release.

Keyword:

drug delivery mPEG-PBAE nanomicelles pH-responsive renal cell carcinoma

Community:

  • [ 1 ] [Wang, Ling]Fujian Med Univ, Fuzhou Univ Affiliated Prov Hosp, Sch Pharm, 134 Dongjie, Fuzhou 350001, Fujian, Peoples R China
  • [ 2 ] [Ruan, Junshan]Fujian Med Univ, Fuzhou Univ Affiliated Prov Hosp, Sch Pharm, 134 Dongjie, Fuzhou 350001, Fujian, Peoples R China
  • [ 3 ] [Wang, Ling]Fujian Prov Hosp, Mol Biol Lab Tradit Chinese Med, Fuzhou, Fujian, Peoples R China
  • [ 4 ] [Ruan, Junshan]Fujian Prov Hosp, Mol Biol Lab Tradit Chinese Med, Fuzhou, Fujian, Peoples R China
  • [ 5 ] [Wang, Ling]Fujian Med Univ, Sch Pharm, Fuzhou, Fujian, Peoples R China
  • [ 6 ] [Cai, Fangqing]Fujian Med Univ, Sch Pharm, Fuzhou, Fujian, Peoples R China
  • [ 7 ] [Li, Yixuan]Fujian Med Univ, Sch Pharm, Fuzhou, Fujian, Peoples R China
  • [ 8 ] [Lin, Xiaolan]Fujian Med Univ, Sch Pharm, Fuzhou, Fujian, Peoples R China
  • [ 9 ] [Wang, Yuting]Fujian Med Univ, Sch Pharm, Fuzhou, Fujian, Peoples R China
  • [ 10 ] [Liang, Weijie]Fujian Med Univ, Sch Pharm, Fuzhou, Fujian, Peoples R China
  • [ 11 ] [Wang, Cunze]Fujian Med Univ, Sch Pharm, Fuzhou, Fujian, Peoples R China
  • [ 12 ] [Ruan, Junshan]Fujian Med Univ, Sch Pharm, Fuzhou, Fujian, Peoples R China
  • [ 13 ] [Liu, Caiyu]Fujian Univ Tradit Chinese Med, Sch Pharm, Fuzhou, Fujian, Peoples R China

Reprint 's Address:

  • 阮君山

    [Ruan, Junshan]Fujian Med Univ, Fuzhou Univ Affiliated Prov Hosp, Sch Pharm, 134 Dongjie, Fuzhou 350001, Fujian, Peoples R China

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Source :

INTERNATIONAL JOURNAL OF NANOMEDICINE

ISSN: 1178-2013

Year: 2024

Volume: 19

Page: 9821-9841

6 . 7 0 0

JCR@2023

Cited Count:

WoS CC Cited Count:

SCOPUS Cited Count:

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 1

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