title: Poly(3-hydroxybutyrate-co-epsilon-caprolactone) copolymers and poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-epsilon-caprolactone) terpolymers as novel materials for colloidal drug delivery systems.
abstract: Poly(3-hydroxybutyrate-co-epsilon-caprolactone) copolymers and poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-epsilon-caprolactone) terpolymers were used by a solvent deposition technique to prepare either micro- or nanoparticles. In particular, the synthesis and analytical characterization of the terpolymers were described.On the basis of copolymer composition and properties, either micro- or nanoparticles were obtained; nanoparticle size was below 500 nm for the suspensions obtained from P(HB-co-CL) copolymers, and even smaller (200-300 nm) for those obtained using terpolymers. Particle size showed only a limited tendency to increase during storage, suggesting a good chemical and physical stability in the short-term storage at room temperature. Some copolymers produced hetero-dispersed microparticles under the same conditions, with a mean size between 10 and 30 microm. These systems showed a tendency to aggregate upon storage at room temperature.The nanoparticles showed a negative surface charge (around -20 mV for those prepared using an UltraTurrax and about -5 mV for those prepared by magnetic stirring). After storage at 4 degrees C the surface charge tend to decrease and these changes have been explained in terms of a partial hydrolysis of the polymeric matrix in aqueous suspension, which led to a change of chemical composition at the surface of the particles.The fluorescent probes calcein and Oil Red O were encapsulated in these systems as models of a hydrophilic and lipophilic drug molecule, respectively. Encapsulation efficiency and in vitro release profiles were studied to evaluate the effect of copolymer properties, such as molecular weight and composition, on their behaviour as potential materials to prepare controlled drug delivery carriers. Calcein was generally better encapsulated (up to 100%) than Oil Red O (10-30%); however, the zeta-potential measurement and in vitro release experiments suggested that a large amount of calcein was adsorbed onto the particle surface and was rapidly released within the first minutes of the test. Conversely, the lipophilic probe was dispersed within the polymeric matrix and its release profile from the nanoparticles was characterized by a considerable lag time (up to 8 h), followed by a slow and almost linear release.As a general trend, we observed that the composition and crystallinity of the tested polymers affected the type and size of obtained systems (micro- or nanoparticles), whereas the molecular weight mainly influenced the probes encapsulation and release.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Catania, Città Universitaria, Viale A. Doria, 6, I-95125 Catania, Italy. r.pignatello@unict.it
authors.forename: Rosario
authors.initials: R
authors.lastname: Pignatello
authors.forename: Teresa
authors.initials: T
authors.lastname: Musumeci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Impallomeni
authors.forename: Giovanni Marco
authors.initials: GM
authors.lastname: Carnemolla
authors.forename: Giovanni
authors.initials: G
authors.lastname: Puglisi
authors.forename: Alberto
authors.initials: A
authors.lastname: Ballistreri
mesh_terms: D001391:Azo Compounds / Q000737:chemistry; D003102:Colloids / Q000737:chemistry*; D004396:Coloring Agents / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005079:Excipients; D005452:Fluoresceins / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008970:Molecular Weight; D053758:Nanoparticles; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D012995:Solubility; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013056:Spectrophotometry, Ultraviolet; D000094122:Polyhydroxybutyrates
chemical_list: D001391:Azo Compounds; D003102:Colloids; D004396:Coloring Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D005452:Fluoresceins; D011091:Polyesters; C052620:poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate); D000094122:Polyhydroxybutyrates; C476612:poly(3-hydroxybutyrate-co-epsilon-caprolactone); C011049:oil red O; C007740:fluorexon