Biomedical subjects

Joram Slager

Publications and source records attributed to Joram Slager.

4 recordsLinked to original sources

PubMed2004

Hetero-stereocomplexes of D-poly(lactic acid) and the LHRH analogue leuprolide. Application in controlled release.

Reversible hetero-stereoselective complexes were obtained by mixing acetonitrile solutions of enantiomeric D-poly(lactic acid) (d-PLA) and leuprolide, an L-configured nonapeptide LHRH analogue. The complex spontaneously aggregated and precipitated in high yields (95%) from acetonitrile solutions, forming uniform, porous microparticles with a mean unweighed particle size of 1.7 microm. The complexation of L-configured peptide occurred only with D-PLA, and not with L-PLA or racemic D,L-PLA. Various factors affecting the release pattern of leuprolide from the hetero-stereocomplexes were investigated. Complexes with D-PLA of low molecular weight (< 10,000 Da) displayed lower release rates of leuprolide than high molecular weight D-PLA (> 50,000 Da). Changing the leuprolide: D-PLA ratio from 1:50 to 1:10 (w/w) in the stereocomplex, resulted in a faster release of leuprolide. Similarly, the release rate of leuprolide was twice as fast when adding poly(ethylene glycol) to the acetonitrile complexation solution. Leuprolide was released from most of the formulations in a first order pattern, with only a small burst release during the first 24 h. Addition of water to the complexation solution significantly increased the initial release of the peptide. Low testosterone levels for over 25 days were observed in an in vivo release study of leuprolide from a hetero-stereocomplex formulation, monitoring testosterone levels in the blood of rats after sub cutaneous injection.

Animals↗

PubMed2003

Biopolymer stereocomplexes.

A polymer stereocomplex is defined as a stereoselective interaction between two complementing stereoregular polymers, that interlock and form a new composite, demonstrating altered physical properties in comparison to the parent polymers. The main interactions, resulting in the complexation, are suggested to rely on stereoselective van der Waals forces. This review focuses mainly on homo-stereocomplexes of poly(methyl methacrylate) homo- and block-copolymers, which are non-degradable biopolymers, and biodegradable poly(lactic acid) (PLA) homo- and block-copolymers and hetero-stereocomplexes between D-configured PLA and L-configured peptides. Topics including physical methods for characterization and visualization and the use as matrices for controlled release, tissue engineering or other biomedical purposes, are discussed for the different stereocomplexes.

Animals↗

PubMedDate not supplied

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.

Calorimetry, Differential Scanning↗

PubMedDate not supplied

Heterostereocomplexes prepared from d-PLA and l-PLA and leuprolide. II. Release of leuprolide.

Reversible stereoselective complexes were spontaneously obtained from mixing acetonitrile solutions of enatiomeric d-poly(lactic acid) (d-PLA), l-poly(lactic acid) (l-PLA), and leuprolide, a l-configured nonapeptide LHRH analogue. The complex spontaneously aggregated and precipitated in high yields (>90%) from acetonitrile solution, forming uniform, porous microparticles. The stereocomplex microparticles showed a continuous release of the interlocked peptide for a period of one to three months under physiological conditions. Various factors, including method of complex formation, molecular weight of PLA, leuprolide:polymer and d-PLA:l-PLA complex ratios, and additives, influenced the release pattern of leuprolide from the stereocomplexes. Continuous release of leuprolide for over 100 days was observed for certain stereocomplex compositions. In vivo evaluation of the leuprolide loaded stereocomplexes in rats by monitoring testosterone levels in the blood of rats after subcutaneous injection showed low testosterone levels for over 42 days.

Animals↗