PEGylated Dendrimer Mediated Delivery of Bortezomib: Drug Conjugation versus Encapsulation

被引:24
|
作者
Sahoo, Rakesh K. [1 ]
Gothwal, Avinash [1 ]
Rani, Sarita [1 ]
Nakhate, Kartik T. [2 ]
Ajazuddin [2 ]
Gupta, Umesh [1 ]
机构
[1] Cent Univ Rajasthan, Sch Chem Sci & Pharm, Dept Pharm, Ajmer 305817, Rajasthan, India
[2] Rungta Coll Pharmaceut Sci & Res, Kohka Kurud Rd, Chhattisgarh 490024, India
关键词
IN-VITRO; POLY(AMIDOAMINE) DENDRIMERS; POLYAMIDOAMINE DENDRIMERS; ANTICANCER DRUG; PROTEASOME; TOXICITY; ASSAY; BIOCOMPATIBILITY; BIODISTRIBUTION; NANOPARTICLES;
D O I
10.1016/j.ijpharm.2020.119389
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Poor aqueous solubility of anticancer drug bortezomib (BTZ) still remains a major challenge in the development of a successful formulation. The dendrimeric platform can provide a better opportunity to deliver BTZ with improved solubility. BTZ encapsulated in PEGylated PAMAM dendrimers (BTZ-PEG-PAMAM) was characterized and evaluated comparatively with encapsulated and conjugated dendritic formulations. The particle size of BTZ-PEG-PAMAM was 188.6 ± 4.17 nm, with entrapment efficiency of 78.61 ± 2.91% and drug loading of 39.30 ± 1.98%. The aqueous solubility of BTZ in PAMAM-PEG conjugate was enhanced by 68.11 folds in comparison to pure drug. In vitro drug release profile was found to be sustained up to 72 h. A comparative colorimetric MTT assay against A549 and MCF-7 cancer cells resulted in maximum efficacy from BTZ-PEG-PAMAM with IC50 value 333.14 ± 15.42 and 152.60 ± 24.56 nM, respectively. Significantly higher cellular internalization was observed in FITC tagged BTZ-PEG-PAMAM. In vivo pharmacokinetic study performed on Sprague Dawley rats resulted in 8.63 folds increase in bioavailability for BTZ-PEG-PAMAM than pure drug. Pharmacokinetic parameters of BTZ-PEG-PAMAM were better and improved over BTZ and other dendritic formulations. In conclusion, the prepared formulation of BTZ-PEG-PAMAM has given significant outcome and this strategy may be further explored for better delivery of BTZ in future. © 2020 Elsevier B.V.
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页数:13
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