ABSTRACT
Condensation of Bu(2)Sn(OMe)(2) with poly(ethylene glycol)s yielded macrocyclic tin alkoxides which were, in turn, used as cyclic initiators for the ring-expansion polymerization of epsilon-caprolactone, D,L-lactide, or trimethylene carbonate. The resulting cyclic triblock copolymers were in situ cross-linked with trimesoyl chloride. The lengths of the A-B-A triblock segments were varied via the monomer-initiator ratio (M/I) or via the lengths of the poly(ethylene glycol)s. After extraction with CH(2)Cl(2), the isolated networks were characterized by (1)H NMR spectroscopy, DSC measurements, and swelling experiments. The release of dexamethasone and 5-fluorouracil from two triblock networks was studied in physiological buffer solutions at 37 degrees C over a period of several weeks. A strong initial burst was found in all cases. Only a weak initial burst and a more continuous release was observed when networks of random L-lactide/epsilon-caprolactone copolymers were studied under the same conditions.
Subject(s)
Absorbable Implants , Drug Delivery Systems/methods , Lactones/chemistry , Lactones/metabolism , Polyethylene Glycols/chemistry , Polymers/chemistry , Polymers/metabolism , Calorimetry, Differential Scanning/methods , Dexamethasone/chemistry , Dioxanes/chemistry , Fluorouracil/chemistry , Lactones/chemical synthesis , Molecular Structure , Organometallic Compounds/chemistry , Polyesters/chemistry , Polymers/chemical synthesis , Tin/chemistryABSTRACT
Spirocyclic tin initiators were prepared by condensation of commercial hydroxyethylated pentaerythritol with Bu(2)Sn(OMe)(2). These tin-containing spirocycles served as initiators for the ring-expansion polymerization of epsilon-caprolactone, beta-D,L-butyrolactone or D,L-lactide. The in situ polycondensation of these expanded spirocycles with terephthaloyl chloride or sebacoyl chloride yielded the desired biodegradable networks with elimination of the Bu(2)Sn group. The segment length (pore size) could be controlled via the monomer-initiator ratio (M/I) of the ring-expansion polymerization. Biodegradable networks were also obtained when Sn-containing spirocyclic polylactones were polycondensed with diphenyl dichlorosilane, benzene phosphonic dichloride, and phenyl phosphoric dichloride.
