Ferulic Acid-Based Polymers with Glycol Functionality as a Versatile Platform for Topical Applications.

Ferulic acid-based polymers with aliphatic linkages have been previously synthesized via solution polymerization methods, yet they feature relatively slow ferulic acid release rates (∼11 months to 100% completion). To achieve a more rapid release rate as required in skin care formulations, ferulic acid-based polymers with ethylene glycol linkers were prepared to increase hydrophilicity and, in turn, increase ferulic acid release rates. The polymers were characterized using nuclear magnetic resonance and Fourier transform infrared spectroscopies to confirm chemical composition. The molecular weights, thermal properties (e.g., glass transition temperature), and contact angles were also obtained and the polymers compared. Polymer glass transition temperature was observed to decrease with increasing linker molecule length, whereas increasing oxygen content decreased polymer contact angle. The polymers' chemical structures and physical properties were shown to influence ferulic acid release rates and antioxidant activity. In all polymers, ferulic acid release was achieved with no bioactive decomposition. These polymers demonstrate the ability to strategically release ferulic acid at rates and concentrations relevant for topical applications such as skin care products.

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.

Antibiotic-containing polymers for localized, sustained drug delivery.

Many currently used antibiotics suffer from issues such as systemic toxicity, short half-life, and increased susceptibility to bacterial resistance. Although most antibiotic classes are administered systemically through oral or intravenous routes, a more efficient delivery system is needed. This review discusses the chemical conjugation of antibiotics to polymers, achieved by forming covalent bonds between antibiotics and a pre-existing polymer or by developing novel antibiotic-containing polymers. Through conjugating antibiotics to polymers, unique polymer properties can be taken advantage of. These polymeric antibiotics display controlled, sustained drug release and vary in antibiotic class type, synthetic method, polymer composition, bond lability, and antibacterial activity. The polymer synthesis, characterization, drug release, and antibacterial activities, if applicable, will be presented to offer a detailed overview of each system.

Locally delivered salicylic acid from a poly(anhydride-ester): impact on diabetic bone regeneration.

Diabetes mellitus (DM) involves metabolic changes that can impair bone repair, including a prolonged inflammatory response. A salicylic acid-based poly(anhydride-ester) (SA-PAE) provides controlled and sustained release of salicylic acid (SA) that locally resolves inflammation. This study investigates the effect of polymer-controlled SA release on bone regeneration in diabetic rats where enhanced inflammation is expected. Fifty-six Sprague-Dawley rats were randomly assigned to two groups: diabetic group induced by streptozotocin (STZ) injection or normoglycemic controls injected with citrate buffer alone. Three weeks after hyperglycemia development or vehicle injection, 5mm critical sized defects were created at the rat mandibular angle and treated with SA-PAE/bone graft mixture or bone graft alone. Rats were euthanized 4 and 12weeks after surgery, then bone fill percentage in the defect region was assessed by micro-computed tomography (CT) and histomorphometry. It was observed that bone fill increased significantly at 4 and 12weeks in SA-PAE/bone graft-treated diabetic rats compared to diabetic rats receiving bone graft alone. Accelerated bone formation in normoglycemic rats caused by SA-PAE/bone graft treatment was observed at 4weeks but not at 12weeks. This study shows that treatment with SA-PAE enhances bone regeneration in diabetic rats and accelerates bone regeneration in normoglycemic animals.

Biodegradable coumaric acid-based poly(anhydride-ester) synthesis and subsequent controlled release.

To overcome drug delivery issues associated with its short half-life in vivo, p-coumaric acid (pCA), a naturally occurring bioactive, has been chemically incorporated into a poly(anhydride-ester) backbone through solution polymerization. Nuclear magnetic resonance and Fourier transform infrared spectroscopies indicated that pCA was successfully incorporated without noticeable alterations in structural integrity. The polymer's weight-average molecular weight and thermal properties were determined, exhibiting a molecular weight of over 26 000 Da and a glass transition temperature of 57 °C. In addition, in vitro hydrolytic release studies demonstrated pCA release over 30 d with maintained antioxidant activity, demonstrating the polymer's potential as a controlled release system.

Formulation of salicylate-based poly(anhydride-ester) microspheres for short- and long-term salicylic acid delivery.

The formulation of salicylate-based poly(anhydride-ester) (PAE) microspheres was optimized by altering polymer concentration and homogenization speed to improve the overall morphology. The microspheres were prepared using three salicylate-based PAEs with different chemical compositions comprised of either a heteroatomic, linear aliphatic, or branched aliphatic moiety. These PAEs broadened the range of complete salicylic acid release to now include days, weeks and months. The molecular weight (M(w)), polydispersity index (PDI) and glass transition temperature (T(g)) of the formulated polymers were compared to the unformulated polymers. In general, the M(w) and PDI exhibited decreased and increased values, respectively, after formulation, whereas the T(g) changes did not follow a specific trend. Microsphere size and morphology were determined using scanning electron microscopy. These microspheres exhibited smooth surfaces, no aggregation, and size distributions ranging from 2-34 m in diameter. In vitro release studies of the chemically incorporated salicylic acid displayed widely tunable release profiles.

Biodegradable ferulic acid-containing poly(anhydride-ester): degradation products with controlled release and sustained antioxidant activity.

Ferulic acid (FA) is an antioxidant and photoprotective agent used in biomedical and cosmetic formulations to prevent skin cancer and senescence. Although FA exhibits numerous health benefits, physicochemical instability leading to decomposition hinders its efficacy. To minimize inherent decomposition, a FA-containing biodegradable polymer was prepared via solution polymerization to chemically incorporate FA into a poly(anhydride-ester). The polymer was characterized using nuclear magnetic resonance and infrared spectroscopies. The molecular weight and thermal properties were also determined. In vitro studies demonstrated that the polymer was hydrolytically degradable, thus providing controlled release of the chemically incorporated bioactive with no detectable decomposition. The polymer degradation products were found to exhibit antioxidant and antibacterial activity comparable to that of free FA, and in vitro cell viability studies demonstrated that the polymer is noncytotoxic toward fibroblasts. This renders the polymer a potential candidate for use as a controlled release system for skin care formulations.

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.