Evaluation of the Release Kinetics of a Pharmacologically Active Substance from Model Intra-Articular Implants Replacing the Cruciate Ligaments of the Knee.

Implants are readily applied as a convenient method of therapy. There is great interest in the prolonged release of active substances from implants. The objective of this work was to evaluate the dissolution kinetics of steroidal anti-inflammatory preparation (SAP) released from novel implants, and to test the influence of the technology on SAP release kinetics. The proposed long-acting preparations may overcome difficulties resulting from repeated injections and often visits to ambulatory clinic, as the stabilizing function of the artificial ligament would be enriched with pharmacological activity. The potential advantages provided by the new coatings of knee implants include the continuous, sustained, and prolonged release of an active substance. The study was carried out using a modified United States Pharmacopoeia (USP) apparatus 4. The amount of SAP was measured spectroscopically. It was revealed that the transport of the drug was mainly a diffusion process. The drug release kinetics was analyzed using zero-, first-, and second-order kinetics as well as Korsmeyer-Peppas, Higuchi, and Hixon-Crowell models. The highest values of the release rate constants were k0 = (7.49 ± 0.05) × 10-5 mg × min-1, k1 = (6.93 ± 0.05) × 10-6 min-1, and k2 = (7.70 ± 0.05) × 10-7 mg-1 × min-1 as calculated according to zero-, first-, and second-order kinetics equations, respectively. The values of the rate constants obtained for the slowest process were k0 = (3.63 ± 0.06) × 10-5 mg × min-1, k1 = (2.50 ± 0.03) × 10-6 min-1, and k2 = (2.80 ± 0.03) × 10-7 mg-1 × min-1. They may suggest the possibility of sustained release of betamethasone from the system. Due to the statistical analysis, differences were observed between most of the studied implants. Incubation, temperature, time of stabilization of layers, and the method of SAP deposition on the matrix affected the drug release.

Reconstruction of cranial cruciate ligament in rabbits using polyester implants saturated with PRP, antlerogenic stem cells MIC-1 and their homogenate.

AIM OF THE STUDY: The attempt to limit the negative effects of polyester implants on the articular cavity by using preparations containing growth factors. MATERIALS AND METHODS: Polyester implants used for the reconstruction of a rabbit's cranial cruciate ligament (CCL) were saturated with autogenic platelet-rich plasma (PRP), antlerogenic stem cells MIC-1 and their homogenate prior to the surgery. Six months after CCL reconstruction, morphological, and biochemical blood tests were carried out, including proteinogram and acute phase proteins. The knee joints were also examined macro- and microscopically. RESULTS: The results, compared to the control group, showed a favorable effect of the PRP and homogenate of antlerogenic cells on limiting the inflammation caused by the presence of polyester implant in the knee joint. The addition of growth factors caused covering the implant faster with the recipient's connective tissue, thus contributing to reducing the inflammatory reaction of the articular capsule to the presence of polyester. At the same time, no enhanced local or general reaction of the rabbit organism was observed to the presence of xenogenic antlerogenic stem cells MIC-1 homogenate which, like the PRP, may provide an easily available source of growth factors, increasingly often used in regenerative medicine. CONCLUSIONS: Applying antlerogenic stem cells, their homogenate or PRP increases the volume of connective tissue that surrounds and intertwines polyester CCL implant, separating it from synovial cavity environment.