A 2.5% Polyacrylamide Hydrogel (PAAG)a was tested for treatment of Osteoarthritis (OA) in a goat model (transection of medial collateral ligament, bisection of medial meniscus and partial-thickness cartilage incisions of medial tibial plateau) with highly encouraging results. The objective was to describe preliminary observations of the mechanisms of action of PAAG in OA joints, based on MRI, pathology and joint capsule elasticity investigations. A randomized controlled study was conducted on an OA knee model in goats: treatment group (intraarticular PAAG), control group (intraarticular saline). Magnetic Resonance Imaging (MRI) was performed prior to surgery, 3, 4, 5 and 7 months post-surgery. Seven months post-surgery, gross pathology and histopathology, including immunohistochemistry for nerve endings, were performed on both knees. Joint capsule elasticity of the knees was measured in both groups.

MRI showed reduction followed by stabilization of OA lesions after PAAG treatment. At gross pathology, PAAG was seen adhering to synovial membrane. Histopathology showed that intraarticular PAAG injection added to the thickness of the synovial membrane by allowing angiogenesis, collagen and synovial cell increase; PAAG was integrated into the synovial membrane. Nerve endings were intact with normal morphology and numbers. Joint capsule elasticity investigation showed that treated knees had a higher elasticity when compared to control knees. This study presents preliminary observations of the mechanisms of action of PAAG on OA joints: (1) Pathology and joint capsule elasticity suggest that PAAG by acting on synovial membrane may reduce overall joint capsule stiffness, a major source of pain in OA. (2) MRI and pathology revealed stabilization of OA lesions in PAAG treated goats, possibly caused by the high viscosupplementation of PAAG.

Sitagliptin is a dipeptidyl peptidase 4-(DPP-4) inhibitor with glucose controlling capabilities that was effectively used for treating diabetes in the past. However, the oral administration of this drug caused such severe side effects that it was removed from the market. In the present study, Sitagliptin was formulated in a gel-type reservoir on a transdermal patch device, optimized by a mathematical simulation methodology, and experimentally validated in vitro using a Franz Cell apparatus. The mathematical model determined optimal design parameters which included 1% w/w acellulose as drug reservoir, transdermal patch rate control membranes, 1.25 mM initial drug concentration, 2 mL initial volume, and 4.52 cm2 patch area. This optimized reservoir formulation was then fabricated in the transdermal patch system and tested using Franz Cell to validate the simulation. The experimental results from the fabricated transdermal patch system indicated that Sitagliptin can be formulated in a patch to achieve the target effective plasma drug concentration in less than one hour and is able to sustain glucose control for over 24 hours.