Controlled Release of Octreotide and Assessment of Peptide Acylation from Poly(D,L-lactide-co-hydroxymethyl glycolide) Compared to PLGA Microspheres

# The Author(s) 2011. This article is published with open access at Springerlink.com Purpose To investigate the in vitro release of octreotide acetate, a somatostatin agonist, from microspheres based on a hydrophilic polyester, poly(D,L-lactide-co-hydroxymethyl glycolide) (PLHMGA). Methods Spherical and non-porous octreotide-loaded PLHMGA microspheres (12 to 16 μm) and loading efficiency of 60–70% were prepared by a solvent evaporation. Octreotide release profiles were compared with commercial PLGA formulation (Sandostatin LAR ®); possible peptide modification with lactic, glycolic and hydroxymethyl glycolic acid units was monitored. Results PLHMGA microspheres showed burst release (~20%) followed by sustained release for 20–60 days, depending on the hydrophilicity of the polymer. Percentage of released loaded peptide was high (70–90%);>60 % of released peptide was native octreotide. PLGA microspheres did not show peptide release for the first 10 days, after which it was released in a sustained manner over the next 90 days;>75 % of released peptides were acylated adducts. Conclusions PLHMGA microspheres are promising controlled systems for peptides with excellent control over release kinetics. Moreover, substantially less peptide modification occurred in PLHMGA than in PLGA microspheres. KEY WORDS acylation. aliphatic polyester. controlle

Multilamellar or multivesicular vesicles?

Recently attention in liposome preparation technology has been focused on the preparation of liposomes with a large number of bilayers. These liposomes offer the possibility to encapsulate large amounts of hydrophobic drugs. All methods used to prepare these vesicles are modifications of the method used to produce reversephase evaporation vesicles (REV), as described first by Szoka and Papahadjopoulos (1978). The names for these multi-layered vesicles are: stable plurilamellar vesicles (SPLV), multilayered REV (MLV-REV) and multilamellar vesicles. In order to avoid confusion we will refer to the vesicles prepared by Bangham et al. as multilamellar vesicles (MLV) and to those multilayered vesicles prepared by emulsion techniques as REV-MLV. Gruner et al. compared the physical characteristics of MLV and SPLV. They found that these vesicles had different properties for stability, entrapment efficiency and biological effects, even if they were made from the same materials and appeared quite similar in the electron microscope.multilamellar vesicl