Biocompatible photocrosslinked poly(ester anhydride) based on functionalized poly(epsilon-caprolactone) prepolymer shows surface erosion controlled drug release in vitro and in vivo.
Star-shaped poly(epsilon-caprolactone) oligomers functionalized with succinic anhydride were used as prepolymers to prepare photocrosslinked poly(ester anhydride) to evaluate their in vivo drug delivery functionality and biocompatibility. Thus, in this work, erosion, drug release and safety of the photocrosslinked poly(ester anhydride) were examined in vitro and in vivo. A small water-soluble drug, propranolol HCl (M(w) 296 g/mol, solubility 50 mg/ml), was used as the model drug in an evaluation of the erosion controlled release. Drug-free and drug-loaded (10-60% w/w) poly(ester anhydride) discoids eroded in vitro (pH 7.4 buffer, +37 degrees C) linearly within 24-48 h. A strong correlation between the polymer erosion and the linear drug release in vitro was observed, indicating that the release had been controlled by the erosion of the polymer. Similarly, in vivo studies (s.c. implantation of discoids in rats) indicated that surface erosion controlled drug release from the discoids (drug loading 40% w/w). Oligomers did not decrease cell viability in vitro and the implanted discoids (s.c., rats) did not evoke any cytokine activity in vivo. In summary, surface erosion controlled drug release and the safety of photocrosslinked poly(ester anhydride) were demonstrated in this study.
Mönkäre
J
J
School of Pharmacy, Pharmaceutical Technology, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland. juha.monkare@uef.fi
Hakala
R A
RA
Vlasova
M A
MA
Huotari
A
A
Kilpeläinen
M
M
Kiviniemi
A
A
Meretoja
V
V
Herzig
K H
KH
Korhonen
H
H
Seppälä
J V
JV
Järvinen
K
K
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival; D003692:Delayed-Action Preparations / Q000737:chemistry*; D006801:Humans; D008297:Male; D010777:Photochemistry; D011091:Polyesters / Q000737:chemistry*; D011433:Propranolol / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D011091:Polyesters; C016240:polycaprolactone; D011433:Propranolol