Controlled release of low-molecular weight, polymer-free corticosteroid coatings suppresses fibrotic encapsulation of implanted medical devices.

Inflammation-driven foreign body reactions, and the frequently associated encapsulation by fibrogenic fibroblasts, reduce the functionality and longevity of implanted medical devices and materials. Anti-inflammatory drugs, such as dexamethasone, can suppress the foreign body reaction for a few days post-surgery, but lasting drug delivery strategies for long-term implanted materials remain an unmet need. We here establish a thin-coating strategy with novel low molecular weight corticosteroid dimers to suppress foreign body reactions and fibrotic encapsulation of subcutaneous silicone implants.

Polymer-free corticosteroid dimer implants for controlled and sustained drug delivery.

Polymeric drug carriers are widely used for providing temporal and/or spatial control of drug delivery, with corticosteroids being one class of drugs that have benefitted from their use for the treatment of inflammatory-mediated conditions. However, these polymer-based systems often have limited drug-loading capacity, suboptimal release kinetics, and/or promote adverse inflammatory responses. This manuscript investigates and describes a strategy for achieving controlled delivery of corticosteroids, based on a discovery that low molecular weight corticosteroid dimers can be processed into drug delivery implant materials using a broad range of established fabrication methods, without the use of polymers or excipients.

Highly Bioactive SDF-1α Delivery from Low-Melting-Point, Biodegradable Polymer Microspheres.

Aliphatic polyester biodegradable microspheres have been extensively studied for controlled and minimally invasive in situ protein delivery. However, they are commonly characterized by protein denaturation via acidic polyester degradation products, whereas their supraphysiologic modulus contributes to the inflammatory response upon implantation. To address these limitations, low-melting-point poly(ε-caprolactone--glycolide)--poly(ethylene glycol)--poly(ε-caprolactone--glycolide) (PEG-(PCG)) copolymers were prepared and characterized for their ability to release bioactive stromal-derived factor-1α (SDF-1α) as a representative therapeutic protein.

Development of PVP/PEG mixtures as appropriate carriers for the preparation of drug solid dispersions by melt mixing technique and optimization of dissolution using artificial neural networks.

The effect of plasticizer's (PEG) molecular weight (MW) on PVP based solid dispersions (SDs), prepared by melt mixing, was evaluated in the present study using Tibolone as a poorly water soluble model drug. PEGs with MW of 400, 600, and 2000 g/mol were tested, and the effect of drug content, time and temperature of melt mixing on the physical state of Tibolone, and the dissolution characteristics from SDs was investigated. PVP blends with PEG400 and PEG600 were completely miscible, while blends were heterogeneous.