Heterostereocomplexes prepared from d-poly(lactide) and leuprolide. I. Characterization.
Heterostereocomplexes between d-PLA and l-peptides, obtained by spontaneous precipitation from acetonitrile solution, were characterized by thermal analysis and microscopic techniques. Differential scanning calorimetry showed two transition endotherms, one for the alpha form that melts at 178 degrees C and one for the beta form of PLA that melts at 169 degrees C. A linear correlation was found between the enthalpy of both melt temperatures and the peptide concentration. The complexation was monitored by a change in morphology, which was imaged by AFM-tapping mode. The initial fibrous network of d-PLA changed to uniform disks of 100 nm in diameter and 2.5 nm in height of the heterostereocomplex. Rhodamine B labeled leuprolide was complexed selectively to d-PLA, which was chemically bound onto mica plates. Addition of l-PLA to the complex enabled displacement of the peptide, which was observed by fluorescent spectrometry and confocal microscopy. These results provide a method, which enables one to obtain an expression for the relative interaction strength between various stereoselective polymers and polypeptides with opposite enantiomeric configuration.
Slager
Joram
J
Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Hebrew University, Campus Ein Karem, Jerusalem 91120, Israel.
Domb
Abraham J
AJ
D002152:Calorimetry, Differential Scanning; D011232:Chemical Precipitation; D004337:Drug Carriers / Q000737:chemistry*; D016729:Leuprolide / Q000008:administration & dosage / Q000737:chemistry*; D018613:Microscopy, Confocal; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry; D044367:Phase Transition; D011091:Polyesters / Q000737:chemistry*; D013237:Stereoisomerism
D004337:Drug Carriers; D010455:Peptides; D011091:Polyesters; C033616:poly(lactide); D016729:Leuprolide