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Tamoxifen‐Loaded Polymeric Micelles: Preparation, Physico‐Chemical Characterization and In Vitro Evaluation Studies
Author(s) -
Cavallaro Gennara,
Maniscalco Laura,
Licciardi Mariano,
Giammona Gaetano
Publication year - 2004
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.200400089
Subject(s) - micelle , amphiphile , chemistry , tamoxifen , drug delivery , solubility , peg ratio , copolymer , critical micelle concentration , polymer chemistry , chemical engineering , organic chemistry , polymer , aqueous solution , medicine , cancer , breast cancer , engineering , finance , economics
Abstract Summary: Several samples of polymeric micelles, formed by amphiphilic derivatives of PHEA, obtained by grafting into polymeric backbone of PEGs and/or hexadecylamine groups (PHEA‐PEG‐C 16 and PHEA‐C 16 ) and containing different amount of Tamoxifen, were prepared. All Tamoxifen‐loaded polymeric micelles showed to increase drug water solubility. TEM studies provided evidence of the formation of supramolecular core/shell architectures containing drug, in the nanoscopic range and with spherical shape. Samples with different amount of encapsulated Tamoxifen were subjected to in vitro cytotoxic studies in order to evaluate the effect of Tamoxifen micellization on cell growth inhibition. All samples of Tamoxifen‐loaded polymeric micelles showed a significantly higher antiproliferative activity in comparison with free drug, probably attributable to fluidification of cellular membranes, caused by amphiphilic copolymers, that allows a higher penetration of the drug into tumoral cells. To gain preliminary information about the potential use of prepared micelles as Tamoxifen drug delivery systems, studies evaluating drug release ability of micelle systems in media mimicking biological fluids (buffer solutions at pH 7.4 and 5.5) and in human plasma were carried out. These studies, performed evaluating the amount of Tamoxifen that remains in solution as a function of time, showed that at pH 7.4, as well as in plasma, PHEA‐C 16 polymeric micelles were able to release lower drug amounts than PHEA‐PEG 5000 ‐C 16 ones, while at pH 5.5, the behavior difference between two kind of micelles was less pronounced.