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Cited by 319

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Polylactide−Poly(ethylene glycol) Copolymers as Drug Delivery Systems. 1. Characterization of Water Dispersible Micelle-Forming Systems

Hagan, S. A., Coombes, A. G. A., Garnett, M. C., Dunn, S. E., Davies, M. C., Illum, L., Davis, S. S., Harding, S. E., Purkiss, S., Gellert, P. R.·1996·Langmuir
DOI 10.1021/la950649v
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Abstract

Copolymers of polylactide and poly(ethylene glycol) (PLA−PEG), which self-disperse in water to form spherical nonionic micelles, have been investigated as a novel biodegradable drug delivery system. These copolymers are defined by the molecular weight ratios of their polylactide to poly(ethylene glycol) components (1.5:2 PLA−PEG and 2:5 PLA−PEG) and gave two peaks when purified by gel permeation chromatography (GPC). The first peak consisted of spherical micelles with a diameter of 15.6 nm for 1.5:2 PLA−PEG, and 18.9 nm for 2:5 PLA−PEG micelles after analysis by dynamic light scattering (DLS) and by transmission electron microscopy (TEM). The second peak was a PLA-depleted species resulting from the synthesis and did not form micelles. Testosterone and sudan black B (SBB), which have different hydrophobicities, were used as “model drugs” to evaluate the drug loading ability of the micelles. Ultracentrifugation sedimentation velocity studies confirmed that solubilization of the model drugs had occurred by micellar incorporation. Higher drug loading was obtained for the 1.5:2 PLA−PEG micelles (63.9% (w/w) of SBB, 0.74% (w/w) of testosterone) than for the 2:5 PLA−PEG micelles (59.0% (w/w) of SBB, 0.34% (w/w) of testosterone). The amount of testosterone solubilized was therefore significantly lower than SBB for both copolymers. Stability testing in the presence of salt suggested that the micelles had sterically stabilized surfaces. In vivo studies in the rat, using a radioactive marker, showed that PLA−PEG micelles demonstrated extended circulation times in the blood during the period of study (3 h). The 1.5:2 PLA−PEG showed increased blood levels and lower uptake of the micelles by the liver compared to the 2:5 PLA−PEG micelles. This is thought to be due to differences in the packing density of the copolymer molecules on the micelle surface.

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Metadata

Authors
Hagan, S. A., Coombes, A. G. A., Garnett, M. C., Dunn, S. E., Davies, M. C., Illum, L., Davis, S. S., Harding, S. E., Purkiss, S., & Gellert, P. R.
Venue
Langmuir
Publisher
American Chemical Society (ACS)
Published
1996-01-01
Volume
12
Issue
9
Pages
2153-2161
ISSN
  • 0743-7463 (ISSN-L)
  • 1520-5827
DOI
10.1021/la950649v
OpenAlex
W2017640513
Cited by
319
References
1
FWCI
8.35
Type
journal article
Language
en
Open access
closed

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