Novel poly(hydroxyalkanoates)-based composites containing Bioglass® and calcium sulfate for bone tissue engineering.

Three different poly(hydroxyalkanoates) (PHAs), copolymers of poly(3-hydroxybutyrate) (P3HB), have been used to make composites using two different fillers, bioactive glass (type 45S5 Bioglass®) and calcium sulfate dihydrate. The PHAs used were poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [PHBHV] and two copolymers of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [PHBHHx]. The aim of the study was the fabrication and characterization of the new composites and the assessment of the influence of the particular filler combination on the physical properties and bioactivity of the films. The thermal behaviour was studied using differential scanning calorimetry while mechanical properties were evaluated using dynamic mechanic thermal analysis and tensile strength test. The mechanical and thermal properties were affected by particles addition. The distribution of the particles in the polymer matrix, observed by scanning electron microscopy, was directly related to the mechanical properties. The surface characteristics were investigated by contact angle measurements and Raman spectroscopy. The extent of formation of hydroxyapatite (HA) upon immersion in simulated body fluid (SBF) depended on the polymer used, the amount of fillers employed and the time of immersion in SBF. Bioactivity was enhanced in the composites with a rise of hydrophilicity. The HA formation was controllable with time in the case of PHBHHx composites.

A novel controlled drug delivery system based on pH-responsive hydrogels included in soft gelatin capsules.

pH-sensitive hydrogels based on methacrylic acid (MAA) and poly(ethylene glycol) macromonomer (PEGMEMA) entrapping diltiazem hydrochloride (DIL·HCl) were synthesized inside soft gelatin capsules for use as a new dosage form for oral drug administration. Different monomer compositions were used to evaluate their swelling and release behavior in two media: at low pH, simulating the acid pH of the stomach, and at pH 7, simulating the higher pH environment of the intestine. Both the swelling process and DIL·HCl release strongly depended on pH and monomer composition. Hydrogels with intermediate compositions showed diminished DIL·HCl release at pH 1.2. This fact was related to the formation of an impermeable outer skin, observed by magnetic resonance imaging (MRI). At pH 7 similar shaped release profiles were found for the four hydrogel compositions under investigation. At this neutral pH slow protonation of the carboxylate groups of MAA led to a swelling front and a dry core, also observed by MRI. As a consequence of this anomalous swelling, release curves exhibited a long period of zero order kinetics. This shows that the system could be a suitable candidate to develop a zero order release dosage form for oral administration of DIL·HCl. The swelling and dissolution processes were analyzed by different mathematical approaches.