In Vitro Degradation of an Aromatic Polyanhydride with Enhanced Thermal Properties.

Polyanhydrides have been studied as a drug delivery vehicles due to their surface-eroding behavior which results in zero-order release. However, many polyanhyrides have thermal and solubility properties that make them difficult to formulate for these applications. Poly[α,α'-bis(ortho-carboxyphenoxy)-para-xylene] (oCPX) is an aromatic polyanhydride that has thermal and solubility properties enabling facile processing. The polymer's in vitro degradation profile exhibited an induction period up to 10 days in which degradation product concentration in the media was minimal, followed by a period of stable release of the biocompatible degradation product. Scanning electron microscope images and molecular weight changes of the polymer matrices confirm that this polymer is primarily surface-eroding. The combination of thermal properties, solubility, polymer degradation time, and erosion mechanism indicate that poly(oCPX) is be a suitable matrix candidate for extended, controlled drug delivery.

Poly(anhydride-ester) and poly(N-vinyl-2-pyrrolidone) blends: salicylic acid-releasing blends with hydrogel-like properties that reduce inflammation.

Polymers such as poly(N-vinyl-2-pyrrolidone) (PVP) have been used to prepare hydrogels for wound dressing applications but are not inherently bioactive. For enhanced healing, PVP was blended with salicylic acid-based poly(anhydride-esters) (SAPAE) and shown to exhibit hydrogel properties upon swelling. In vitro release studies demonstrated that the chemically incorporated drug (SA) was released from the polymer blends over 3-4 d in contrast to 3 h, and that blends of higher PVP content displayed greater swelling values and faster SA release. The polymer blends significantly the inflammatory cytokine, TNF-α, in vitro without negative effects.

Tunable drug release profiles from salicylate-based poly(anhydride-ester) matrices using small molecule admixtures.

Poly(anhydride-esters) with salicylic acid, a nonsteroidal anti-inflammatory drug, chemically incorporated into the polymer backbone provide high inherent drug loading. These poly(anhydride-esters) hydrolytically degrade to release salicylic acid over extended time periods (>30 days); however, an initial lag period of no salicylic acid release is observed. This lag period could be unfavorable in applications where immediate salicylic acid release is desired. Poly(anhydride-esters) with short (2 days) and long (11 days) lag periods were admixed with various small molecules as a means to shorten or eliminate the lag period. Salicylic acid, larger salicylic acid prodrugs, and 1:1 combinations of the two were physically admixed, each at 1%, 5%, and 10% (w/w). All admixtures resulted in immediate salicylic acid release and a decrease in glass transition temperatures compared to polymer alone. By varying the amounts of salicylic acid and salicylic acid prodrugs incorporated into the polymer matrix, immediate and constant salicylic acid release profiles over varied time periods were achieved.