Core-shell structured gel-nanocarriers for sustained drug release and enhanced antitumor effect.
The present paper attempted to develop temperature-sensitive and core-shell structured gel-nanocarriers (gel-NCs) for paclitaxel (PTX) with 12-hydroxystearic acid (12-HSA) as an organic gelator, which aims at sustaining drug release over time and thus improves the therapeutic effect. The gel-NCs were prepared by a mechanical mixing and high-pressure homogenization method. The gelation transition temperature (Tgel) of the organic phase contained in the cores of the gel-NCs was optimized by a stirring method. The gel-NCs were characterized in terms of the particle size, morphology and in vitro drug release. The in vivo studies, including the antitumor effects on H22 tumor-bearing mice, biocompatibility and toxicity in mice, were performed. Gel-NCs with approximately 170 nm were prepared successfully, and the gelation of the liquid cores at 37°C was achieved, while the amount of gelator was 3.75% (w/w). Due to the gelation of the cores, sustained drug release over time was obtained. Moreover, the PTX-loaded gel-NCs suppressed tumor growth more efficiently than the conventional nanocarriers with better in vivo biocompatibility and no toxicity to other healthy organs. In conclusion, the 12-HSA organogel-based NCs appear to be promising systems for the sustained release of active compounds for a long time and thus improve the therapeutic outcome.
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Wei
W
He
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Yaqi
Y
Lv
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Yaping
Y
Zhao
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Chaoran
C
Xu
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Zhu
Z
Jin
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Chao
C
Qin
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: lifangyin@hotmail.com.
Lifang
L
Yin
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D005782:Gels; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D010316:Particle Size; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels
12-Hydroxystearic acid (PubChem CID: 7789); Acetone (PubChem CID: 180); Biocompatibility; Calcium dichloride (PubChem CID: 5284359); Core–shell nanoparticles; Coumarin-6 (PubChem CID: 100334); Oleoyl macrogol-6 glycerides (PubChem CID: 6435863); Organogel; Paclitaxel; Paclitaxel (PubChem CID: 44155032); Phosphotungstic acid (PubChem CID: 16212977); Polysorbate 80 (PubChem CID: 5281955); Sustained drug release; Trehalose (PubChem CID: 7427); Trypsin (PubChem CID: 72699210); Tumor therapy