Poly(3-hydroxybutyrate-co-ε-caprolactone) copolymers and poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-ε-caprolactone) terpolymers as novel materials for colloidal drug delivery systems

Poly(3-hydroxybutyrate-co-ε-caprolactone) copolymers and poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-epsilon-caprolactone) terpolymers were used by a solvent deposition technique toprepare either micro- or nanoparticles. In particular, the synthesis and analytical characterization of theterpolymers were described.On the basis of copolymer composition and properties, either micro- or nanoparticles were obtained;nanoparticle size was below 500nm for the suspensions obtained from P(HB-co-CL) copolymers, andeven smaller (200–300 nm) for those obtained using terpolymers. Particle size showed only a limitedtendency to increase during storage, suggesting a good chemical and physical stability in the short-termstorage at roomtemperature.Somecopolymers producedhetero-dispersed microparticles under thesameconditions, with a mean size between 10 and 30 microm. These systems showed a tendency to aggregate uponstorage at room temperature.The nanoparticles showed a negative surface charge (around −20mV for those prepared using an Ultra-Turrax and about −5mV for those prepared by magnetic stirring). After storage at 4 ◦C the surface chargetend to decrease and these changes have been explained in terms of a partial hydrolysis of the polymericmatrix in aqueous suspension, which led to a change of chemical composition at the surface of theparticles.The fluorescent probes calcein and Oil Red O were encapsulated in these systems as models of ahydrophilic and lipophilic drug molecule, respectively. Encapsulation efficiency and in vitro release profileswere 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 generallybetter encapsulated (up to 100%) than Oil Red O (10–30%); however, the zeta-potential measurementand in vitro release experiments suggested that a large amount of calcein was adsorbed onto the particlesurface and was rapidly released within the first minutes of the test. Conversely, the lipophilic probe wasdispersed within the polymeric matrix and its release profile from the nanoparticles was characterizedby 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 affectedthe type and size of obtained systems (micro- or nanoparticles), whereas the molecular weight mainlyinfluenced the probes encapsulation and release.