期刊
ACS APPLIED BIO MATERIALS
卷 2, 期 11, 页码 4728-4736出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsabm.9b00423
关键词
hyaluronic acid; Tacrolimus; adipic dihydrazide; acid-responsive drug delivery; sustained release
资金
- CSIR-New Delhi
- ICMR, India
- IIIM communication [CSIR-IIIM/IPR/0090]
- [DST-EMR/2016/002304]
- [DST-EEQ/2016/000102]
Polymer-drug conjugates have been the cornerstone of several drug delivery systems owing to their numerous benefits such as improved drug solubilization, controlled release, increased efficacy, and improved pharmacokinetics. Herein, an acid-responsive macromolecular prodrug was synthesized by conjugation of Tacrolimus (TAC; FK506) with chemically modified hyaluronic acid (HA), and its physicochemical and pharmacokinetic properties were studied in detail. The prepared conjugate (HA-ADH-TAC) showed 1% drug loading, sustained drug release, and significantly enhanced solubility for the investigated drug. Additionally, cellular uptake study indicated augmented uptake of this conjugate, and hemolysis assay showed biocompatibility of the developed prodrug. Further, the pharmacokinetic behavior of the conjugate was investigated, and it was observed that pharmacokinetic parameters with the conjugate were improved. The results indicate that the developed HA-tacrolimus conjugate has the edge over the plain drug in terms of improved physicochemical properties and favorable pharmacokinetic response.
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