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The synthesis and characterization of a photocurable biodegradable elastomer as a potential biomaterial for the delivery of thermosensitive drugs are described. The elastomer was prepared from UV initiated cross-linking of an acrylated star-poly(ε-caprolactone-co-d,l-lactide) prepolymer. The influence of the molecular weight of the acrylated prepolymer on the final elastomer mechanical and thermal properties was determined. The glass-transition temperature of the elastomers was independent of the prepolymer molecular weight and was from −6 to −8 °C. The Young's modulus and stress at break of the elastomers was proportional to the inverse of the prepolymer molecular weight, while the strain at break increased in a linear fashion with the prepolymer molecular weight. Over a degradation period of 12 weeks in phosphate buffered saline, the elastomers exhibited little mass loss, appreciable mechanical strength loss, and little dimensional or strain at break change.

Degrading hydroxyethylmethacrylate‐grafted dextran (dex‐HEMA) hydrogels generate a relatively sudden increase in osmotic pressure upon degradation into dextran solutions. This phenomenon is currently being examined as a possible means of developing a pulsatile drug‐delivery system. Here a mathematical model based on scaling concepts is presented to describe this sudden increase in swelling pressure and to provide a framework for the rational design of pulsatile delivery systems based on this phenomena. The model provides a good fit to the swelling pressures measured for dex‐HEMA gel/free dextran mixtures that simulate degrading dex‐HEMA gels. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 3397–3404, 2004

Biodegradable elastomers represent a useful class of biomaterials. In this paper, we synthesize thermoset elastomers by utilizing the living nature of ring-opening polymerization of a star copolymer of d,l-lactide and ε-caprolactone initiated with glycerol and catalyzed by stannous 2-ethylhexanoate. The star copolymers were synthesized of varying molecular weight and monomer composition and cross-linked by compression molding using a dilactone, bis(ε-caprolactone-4-yl)propane dissolved in ε-caprolactone monomer. The elastomers were then characterized by differential scanning calorimetry and uniaxial tensile testing and their physical properties related to the nature of the star copolymer prepolymers. The results demonstrate a means of predictably altering the elastomer physical properties by adjusting the star copolymer prepolymer initial molecular weight and monomer ratio.

Camptothecin is an example of a potent drug with a short half-life that would benefit from a localized drug depot system that maintains its stability prior to being released. For this reason, a thermoplastic, biodegradable polymer drug depot was prepared and characterized, and the in vitrorelease of camptothecin examined. ε-Caprolactone oligomers were prepared by ring-opening polymerization initiated by various alcohols. The polymers were characterized via differential scanning calorimeter (DSC) for thermal transitions, and via a parallel plate rheometer for melt viscosity. Camptothecin was loaded into the oligomers and released into PBS buffer. The viscosity of the oligomers was alterable by the initiator used. The oligomers were semi-crystalline with melting points between 37 and 45°C. Camptothecin was released from the oligomers in a diffusion-controlled manner, with the release rate increasing as the melt viscosity of the oligomer decreased. The unreleased camptothecin remained in its active lactone form for a period of up to 16 weeks. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1195–1204, 2004

Injectable thermoplastic oligomers represent a promising biomaterial for drug delivery provided they possess a melting point at or very near physiologic temperature, as well as a low melt viscosity. One approach would be to prepare an oligolactone. In this paper, we examine the role of different alcohol initiators used in the ring-opening polymerization of ε-caprolactone oligomers on the melting point and melt viscosity of the resultant thermoplastics. We found that the initiator used plays a significant role in the final properties of the final oligomer. For primary alcohols, the longer the chain length of the oligomer the lower its melt viscosity, until a chain length of 8 carbons, after which there was no noticeable effect. There was no significant effect observed of primary initiators on the melting point. The use of secondary alcohols produced oligomers with higher viscosities but with reduced overall crystallinity. The use of an unsaturated alcohol, oleyl alcohol, not only reduced the melting point and overall crystallinity but also reduced the melt viscosity of the oligomer. The oleyl alcohol initiated oligomer appears to be a promising vehicle for localized, sustained drug delivery applications.

Swelling pressure measurements were performed on degrading dextran hydroxyethyl methacrylate (dex-HEMA) hydrogels. In these networks, the cross-links are hydrolyzable carbonate ester bonds formed between methacrylate groups and dextran molecules. It is demonstrated that dex-HEMA gels made in the presence of a known amount of free dextran chains exhibit osmotic properties similar to those of partially degraded dex-HEMA gels. The swelling pressure, Πsw, of degrading dex-HEMA gels is controlled primarily by the cross-linked dex-HEMA polymer and the free dextran molecules, while the contribution of short poly-HEMA fragments (produced in the degradation process) is negligible. It is found that Πsw only slightly changes during the first 15 days of degradation. Close to the end of the degradation process, however, a much faster increase in Πsw is observed. The swelling pressure profile of these gels strongly depends on the concentration of the cross-linked dex-HEMA and its chemical composition (amount of HEMA groups per 100 glucose units).

Camptothecin has shown significant antitumor activity to lung, ovarian, breast, pancreas, and stomach cancers. Camptothecin, however, like a number of other potent anticancer agents such as paclitaxel, is extremely water insoluble. Furthermore, pharmacology studies have determined that prolonged schedules of administration given continuously are required. Thus, this insolubility has restricted its clinical application. For these reasons, a number of water-soluble analogs have been synthesized and a number of different formulation approaches have been investigated. In this review, we examine each of these approaches and discuss their advantages and limitations.

The ability of an obstruction-scaling model of solute diffusion to account for solute diffusivity in polyelectrolyte gels composed of semiflexible chains is presented. The diffusion of FITC−dextran in poly(acrylic acid) gels was measured at different pH conditions to determine the effect of the ionization degree of the poly(acrylic acid) on the diffusivity of the FITC−dextran. The obstruction-scaling model, as well as a hydrodynamic-based model and a jumping frequency model, was applied to the data. It was determined through regression analysis that the obstruction-scaling approach provided a better fit and could effectively account for the observed effect of the variation in the ionization degree on solute diffusivity.

An obstruction-scaling model of the diffusion of solute molecules within polyelectrolyte gels is presented. Two release medium conditions are considered: low ionic strength and high ionic strength. The model is tested against experimental data of protein diffusion in calcium alginate hydrogels. The model provides very good agreement to the experimental results, successfully predicting the effects of polymer concentration, release medium ionic strength, and polymer chain flexibility.

A mathematical description of the restricted movement a solute experiences while diffusing in a homogeneous hydrogel is presented. The model is based on the premise that physical obstruction effects dominate the diffusive process, and a scaling law expression is incorporated to describe the distance between cross-links in the polymer network. The model was compared to experimental data taken from literature sources and found to provide good agreement to the effects of both polymer volume fraction and solute size on the diffusivity of a solute within the hydrogel.

Polymer microbead production by parallel plate electrostatic extrusion is presented. Factors affecting microbead size such as needle gauge, electrostatic potential, distance between needle and collecting solution, and polymer solution concentration and flow rate were evaluated. Smaller microbeads resulted from reduced needle diameter, reduced needle to collecting solution distance, increased electrostatic potential, and reduced polymer solution concentration and flow rate. In terms of process scale-up, it was shown that a multi-needle (20) device could continuously produce relatively uniform beads via electrostatics. The technology was demonstrated to be feasible for cell encapsulation or immobilization as there was no detectable effect of applied potential onSpodoptera frugiperda viability.

□ A polymeric delayed-release protein delivery system was investigated with albumin as a model drug. The polysaccharide chitosan was reacted with sodium alginate in the presence of calcium chloride to form microcapsules with a polyelectrolyte complex membrane. Variables believed to be important for membrane formation were examined; these included reaction time, chitosan molecular weight, alginate concentration, chitosan concentration, and solution pH. An alginate-chitosan reaction time, in the range of 10 to 45 min, had no effect on the release of albumin. Increasing the alginate concentration, however, resulted in a decreased rate of release of albumin (from 37% release at 4 h with 1.5% alginate to 20% release with 2.5% alginate). Another key variable was the chitosan molecular weight. The molecular weight of chitosan was varied from 1.25 × 106to 0.25 × 106through a nitrite oxidation reaction with sodium nitrite. Decreasing the molecular weight increased the release of albumin (from 37% release at 4 h with high molecular weight chitosan to 77% release with low molecular weight chitosan). The pH of the extracapsular environment was found to affect the release of albumin significantly (15% release over 24 h at a pH 3.0 and 73% release at pH 8.0). Capsules produced with high molecular weight chitosan and a combination of high and low molecular weight chitosan gave the best results for reducing elution of albumin in the first 4 h and increasing elution in the following 20 h.

Solute diffusion in hydrogels is important in many biotechnology fields. Solute behavior in hydrogels has been explained in terms of reduction in hydrogel free volume, enhanced hydrodynamic drag on the solute, increased path length due to obstruction, and a combination of hydrodynamic drag and obstruction effects. In this article the various mathematical models derived to explain and predict solute diffusion in hydrogels are reviewed and tested against literature data. These models can be divided into those applicable to hydrogels composed of flexible polymer chains (i.e., homogeneous hydrogels) and those composed of rigid polymer chains (i.e., heterogeneous hydrogels). For homogeneous hydrogels it was determined that a scaling hydrodynamic model provided the best explanation for solute diffusion, while for heterogeneous hydrogels obstruction models were more consistent with the experimental data. Both the scaling hydrodynamic model and the most appropriate obstruction model contain undefined parameters which must be clarified in order for these models to gain widespread acceptance.

The release characteristics of protein from chitosan-alginate microcapsules prepared using an electrostatic droplet generator were evaluated. The release studies were undertaken in-vitro in simulated gastrointestinal fluids covering the pH range 1·2-8. Chitosan-alginate microcapsules showed unsatisfactory release properties, losing 94% of the encapsulated proteins (bovine serum albumin) over a 24 h period at pH 1·2. Incorporation of a pH-sensitive polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS), in the microcapsules, by coating the capsule membrane as well as blending with the capsule core polymer in varying ratios, produced significant changes in the release profiles of the microcapsules. At pH 1·2, the modified microcapsules retained up to 60% of the encapsulated protein after 24 h. The results obtained highlight the potential of HPMCAS as a release-modifier in chitosan-alginate microcapsules.