1: Pharmazie. 2008 Mar;63(3):235-40.

Spontaneously self-assembled micelles from poly(ethylene
glycol)-b-poly(epsilon-caprolactone-co-trimethylene carbonate) for drug
solubilization.

Latere DJ, Rouxhet L, Brewster ME, Préat V, Ariën A.

Cordis Corp., Welsh and McKean Roads, Spring House, PA, USA.

Di-block copolymers composed of polyethylene glycol (PEG) and a second block of
(co)polyesters of epsilon-caprolactone (CL) and/or trimethylene carbonate (TMC)
were synthesized and characterized. Tin octoate was used as catalyst and
polymerization were completed over a period of 24 h with high conversion (> 95%).
Self-assembling properties in water were evaluated. All di-block copolymers
behave similarly except when PCL served as the second block. Stable crew-cut
micelles of about 20 nm were obtained by direct dissolution of the liquid
di-block copolymers in water at room temperature. When PCL was present as the
second block, no solubilization occurred. Drug encapsulation of poorly
water-soluble drugs belonging to biopharmaceutics classification system (BCS)
class II (ketoprofen and furosemide) was evaluated. Experimental solubility for
these two drugs shows a significant enhancement such that a maximum value of 23.4
mg/ml was obtained for ketoprofen in a 10% w/v micellar solution as compared to
0.14 mg in water. In the case of furosemide, the solubility increased from 0.04
mg/ml in water to about 3.2 mg/ml in a 10% w/v micellar solution. Enzymatic
degradation of diblock copolymers was also studied in the presence of Pseudomonas
lipase in a phosphate buffer solution (pH 7.4). Results indicated rapid
degradation of copolymers containing relatively higher amounts of CL compared to 
TMC suggesting the potential in vivo degradation.


PMID: 18444514 [PubMed - indexed for MEDLINE]

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