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An affinity-based drug delivery platform for controlling drug release is analyzed by a combination of experimental studies and mathematical modeling. This platform has the ability to form selective interactions between a therapeutic agent and host matrix that yields advantages over systems that employ nonselective methods. The incorporation of molecular interactions in drug delivery can increase the therapeutic lifetime of drug delivery implants and limit the need for multiple implants in treatment of chronic illnesses. To analyze this complex system for rational design of drug delivery implants, we developed a mechanistic mathematical model to quantify the molecular events and processes. With a β-cyclodextrin hydrogel host matrix, defined release rates were obtained using a fluorescent model drug. The key processes were the complexation between the drug and cyclodextrin and diffusion of the drug in the hydrogel. Optimal estimates of the model parameters were obtained by minimizing the difference between model simulation and experimentally measured drug release kinetics. Model simulations could predict the drug release dynamics under a wide range of experimental conditions.

Background Given concern for hernia mesh infection, surgeons often use biologic mesh which may provide reduced risk of infection but at the cost of decreased repair durability. We evaluated mesh coating to provide sustained release of antibiotics to prevent prosthetic mesh infection and also allow a durable repair. Materials and methods Cyclodextrin-based polymer was crosslinked onto multifilament polyester mesh and loaded with vancomycin (1.75 mg/cm2). Pigs received modified meshes (n =6) or normal, untreated meshes (n =4), which were implanted into acute 10 × 5 cm ventral hernia, then directly inoculated with 106 colony-forming unit (CFU) of methicillin-resistant Staphylococcus aureus (MRSA). These were compared to animals receiving normal, uninfected mesh. All mesh was secured in an underlay bridge manner, and after 30 d, the abdominal wall was removed for quantitative bacterial culture and biomechanical analysis. Results All animals survived 30 d. All six animals with coated mesh cleared MRSA infection. The four control animals did not clear MRSA (P =0.005). Quantitative bacterial load was higher in standard mesh versus drug-delivery mesh group (2.34×104 versus 80.9 CFU/gm). These data were log10-transformed and analyzed by Welch’s t-test (P = 0.001). Minimum number of CFUs detectable by assay (300) was used instead of zero. Biomechanical analysis of controls (1.82 N/mm infected; 1.71 N/mm uninfected) showed no difference to the modified meshes (1.31 N/mm) in tissue integration (P = 0.15). Conclusions We successfully prevented synthetic mesh infection in a pig model using a cyclodextrin-based polymer to locally deliver vancomycin to the hernia repair site and clearing antibiotic-resistant bacteria. Polymer coating did not impact the strength of the hernia repair.

Polyesterpolyolacrylate/bentonite nanocomposites, capable of in situ photo polymerization, were synthesized and characterized. The organically modified bentonite clay was prepared by an ion exchange process, in which sodium ions were replaced by alkyl ammonium ions. Organo modification of bentonite was confirmed from X-ray diffraction and fourier transform-infrared data. Microstructures were characterized by XRD data and transmission electron microscopy (TEM). Both XRD data and TEM images of polyester polyol acrylate/organo modified bentonite nanocomposites indicated that most of silicate layers were intercalated into the acrylate matrix. The resulting nanocomposites were characterized by gel content, water equilibrium swell, tensile strength, and in vitro degradation. The results showed that water equilibrium swell and in vitro degradation of these nanocomposites decreased with increase in the clay content. The tensile strength of these nanocomposites also increased with increase in the clay content. Release of two model drugs namely sulfamethoxazole and diclofenac sodium (DS) from these nanocomposites was studied in phosphate buffer saline pH = 7.4 at 37 degrees C. The drug release studies showed that sulfamethoxazole released slower than DS from polyester polyol acrylate nanocomposites. Therefore, these materials may be useful for mucoadhesive drug carriers and other biomedical applications.