PLA stereocomplexes for controlled release of somatostatin analogue.
Reversible stereoselective complexes were spontaneously formed from mixing acetonitrile solutions of enantiomeric D-poly(lactide) (D-PLA), L-poly(lactide) (L-PLA), and octreotide (an octapeptide, somatostatin analogue). Hetero-stereocomplexes of poly (D-lactide) and L-octreotide were obtained by spray freezing of solution of D-PLA and octreotide. An additional transition temperature close to the melting point of enantiomeric PLA was observed in DSC thermogram. The same phenomenon was observed in stereocomplex of D-PLA/L-PLA and octreotide. The enthalpy of both transition temperatures correlate with peptide content in the hetero-stereocomplex. The spray method produced compact and smooth micro particles compared to particles formed by precipitation in acetonitrile solution. The particle size of stereocomplexes was in the range of 1.5 to 4 microm for all formations. Increasing peptide concentration in the stereocomplex increases the release rate of the peptide, and increases polymer degradation rate as monitored by lactic acid release form stereocomplexes.
Bishara
Ashgan
A
The Hebrew University of Jerusalem, 91120 Jerusalem, Israel.
Domb
Abraham J
AJ
D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004055:Differential Thermal Analysis; D005612:Freeze Drying; D006868:Hydrolysis; D019344:Lactic Acid / Q000737:chemistry; D015282:Octreotide / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D013816:Thermodynamics
D018931:Antineoplastic Agents, Hormonal; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D015282:Octreotide