title: Physicochemical aspects of doxorubicin-loaded pH-sensitive polymeric micelle formulations from a mixture of poly(L-histidine)-b-poly(ethylene glycol)/poly(L-lactide)-b-poly(ethylene glycol) [corrected].
abstract: In this study, doxorubicin (DOX) was physically incorporated into pH-sensitive micelles made from a mixture of poly(L-histidine)-b-poly(ethylene glycol)/poly(L-lactide)-b-poly(ethylene glycol) (75/25, wt.%). The DOX-loaded mixed micelles were formulated using dialysis methods and optimal DOX incorporation was achieved at a drug/polymer feed ratio of 0.2 (wt./wt.) when a proper amount of aqueous phase (0.2, v./v.) was added into the common solvent (DMSO) solution, followed by dialysis at 4 degrees C. Based on the results obtained from dynamic light scattering, UV-Vis absorption, and fluorescence experiments, it was demonstrated that the encapsulated drugs were mainly located inside the hydrophobic micelle cores, well protected and inaccessible to the exterior molecules. Under in vitro conditions, although the microstructure of the micelles was altered below pH 8.0 by the encapsulated drugs, the drug-loaded micelles still exhibited a desirable ability to control the drug release in response to tumor extracellular pH.
authors.affiliation: Department of Pharmaceutics & Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84108, USA.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Yin
authors.forename: You Han
authors.initials: YH
authors.lastname: Bae
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003956:Dialysis; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000737:chemistry; D008027:Light; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry; D011506:Proteins / Q000737:chemistry; D012542:Scattering, Radiation; D012997:Solvents / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D007773:Lactates; D008823:Micelles; D011506:Proteins; D012997:Solvents; C088513:poly(lactic acid-ethylene glycol); C480317:polyhistidine-block-polyethylene glycol; D011092:Polyethylene Glycols; D004317:Doxorubicin; D004121:Dimethyl Sulfoxide
references.citation: J Control Release. 2008 Mar 3;126(2):130-8
references.pmid: 18187224
references.citation: Eur J Pharm Biopharm. 1999 Sep;48(2):101-11
references.pmid: 10469928
references.citation: J Control Release. 2005 Mar 2;103(1):137-48
references.pmid: 15710507
references.citation: J Drug Target. 2005 Aug;13(7):391-7
references.pmid: 16308207
references.citation: Pharm Res. 1999 Jun;16(6):841-6
references.pmid: 10397603
references.citation: Crit Rev Ther Drug Carrier Syst. 2003;20(5):357-403
references.pmid: 14959789
references.citation: Adv Drug Deliv Rev. 2006 Dec 1;58(14):1532-55
references.pmid: 17092599
references.citation: Biophys J. 1976 Jan;16(1):27-41
references.pmid: 1244888
references.citation: Macromol Biosci. 2005 Nov 4;5(11):1118-24
references.pmid: 16245269
references.citation: J Control Release. 2001 May 14;72(1-3):71-84
references.pmid: 11389986
references.citation: Nature. 1998 Apr 30;392(6679 Suppl):5-10
references.pmid: 9579855
references.citation: Cancer Res. 1989 Aug 15;49(16):4373-84
references.pmid: 2545340
references.citation: Prog Biophys Mol Biol. 1978;34(3):175-95
references.pmid: 375301
references.citation: J Control Release. 2003 Jul 31;90(3):363-74
references.pmid: 12880703
references.citation: J Control Release. 2007 Nov 6;123(2):109-15
references.pmid: 17894942
references.citation: J Control Release. 2000 Feb 14;64(1-3):143-53
references.pmid: 10640653
references.citation: Bioconjug Chem. 2005 Mar-Apr;16(2):361-8
references.pmid: 15769090
references.citation: J Control Release. 2005 Mar 21;103(2):405-18
references.pmid: 15763623
references.citation: J Biomater Sci Polym Ed. 2004;15(3):343-56
references.pmid: 15147166
references.citation: Eur J Pharm Biopharm. 2008 Jan;68(1):112-28
references.pmid: 17804211
references.citation: Eur J Pharm Sci. 2006 Oct 1;29(2):120-9
references.pmid: 16904301
references.citation: Curr Med Chem Anticancer Agents. 2005 Jan;5(1):1-13
references.pmid: 15720257
references.citation: J Control Release. 2003 Aug 28;91(1-2):103-13
references.pmid: 12932642
references.citation: Angew Chem Int Ed Engl. 2003 Oct 6;42(38):4640-3
references.pmid: 14533151
references.citation: Adv Drug Deliv Rev. 2002 Oct 16;54(7):1015-39
references.pmid: 12384319
references.citation: J Control Release. 2001 Jun 15;73(2-3):137-72
references.pmid: 11516494
references.citation: J Control Release. 2002 Jan 17;78(1-3):155-63
references.pmid: 11772457
references.citation: Pharm Res. 2007 Jan;24(1):1-16
references.pmid: 17109211