期刊
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
卷 41, 期 12, 页码 1954-1961出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/03639045.2015.1011167
关键词
Anti-cancer; chitosan; hydrogel; MCF; melphalan; MTT; poloxamer; PEGylation
资金
- Department of Science and Technology, New Delhi (SERC Division), India under DST-FIST scheme [SR/FST/LSI-434/2010]
- Maulana Azad National Fellowship (MANF) UGC, New Delhi, India
Objective: Although the melphalan (ML) used extensively for the management of breast cancer, its clinical application is limited due to significant hemolytic activity. In the present work, a comparative analysis of two distinct in situ-based thermogelling polymers of PEGylated ML was performed.Methods: Briefly, the PEGylated conjugate of the melphalan (MLPEG 5000) for local and sustained drug release action is loaded into two different thermogelling polymeric systems, namely chitosan- and poloxamer-based systems. The synthesized conjugate was loaded to a chitosan (MLP 5000) and poloxamer-based (MPX-CG) thermogelling injectable hydrogels. These thermogelling hydrogels were evaluated for in vitro hydrolysis, in vitro hemolytic activity. and in vitro anticancer activity.Results: The lower percent cumulative hydrolysis was witness for both the hydrogels. MPX-CG and MLP 5000 hydrogels as predicted had shown lower percent cumulative hydrolysis of 3.310.1 and 1.67 +/- 0.1 after 6h. The percentage hemolysis of MPX-CG and MLP 5000 even at a concentration of 32 mu g/ml was found to be 39.23 +/- 1.24% and 34.23 +/- 2.24%, observed at 1h, respectively. Both the hydrogels showed similar anticancer pattern, the MPX-CG hydrogel showed low cell viability of 8.4 +/- 1.1% at a concentration of 150 mu M and the MLP-5000 hydrogel showed slight higher cell viability (13.12 +/- 5.4%) as compared with MPX-CG hydrogel.Conclusion: Hence, from the present study it can be well understood that both the chitosan- and the poloxamer-based thermogelling hydrogel proves to be an effective drug delivery systems for the delivery of the PEGylated conjugates.
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