Fibrosis is a potentially debilitating disease with high morbidity rates. It is estimated that half of all deaths that occur in the USA are attributed to fibrotic disorders. Fibrotic disorders are characterized primarily by disruption in the extracellular matrix deposition and breakdown equilibrium, leading to the accumulation of excessive amounts of extracellular matrix. Given the potentially high prevalence of fibrosis and the paucity of agents currently available for the treatment of this disease, there is an urgent need for the identification of drugs that can be utilized to treat the disease. Pentoxifylline is a methylxanthine derivative that is currently approved for the treatment of vascular diseases, in particular, claudication. Pentoxifylline has three main properties: improving the rheological properties of blood, anti-inflammatory, and antioxidative. Recently, the effectiveness of pentoxifylline in the treatment of fibrosis via attenuating and reversing fibrotic lesions has been demonstrated in several clinical trials and animal studies. As a result of the limited availability of antifibrotic agents in the long-term treatment of fibrosis that can attenuate and even reverse fibrotic lesions effectively, it would be of particular importance to consider the potential clinical utility of pentoxifylline in the treatment of fibrosis. Thus, this paper discusses the evolving roles of pentoxifylline in the treatment of different types of fibrosis.

The reactions between epoxidized natural rubber (ENR) and a low-molecular weight palm oil-based alkyd (A1) have been investigated. Experimental results (FTIR and toluene swelling tests) showed that the alkyd having both hydroxyl and carboxylic groups could react with the epoxide groups of ENR at ambient temperature to cause crosslinking. To establish the predominant reaction, alkyd A1 was chemically modified to vary the amount of hydroxyl and carboxylic groups. A1 was treated with maleic anhydride under two different temperatures of 130 and 185 C. At 130 C, the anhydride has reacted partially with the hydroxyl groups to produce alkyd A2 with higher carboxylic content and lower hydroxyl content. On the other hand, at 185 C, the anhydride has reacted completely to produce alkyd A3 with similar carboxylic acid content as A1 but lower hydroxyl content. Subsequent reactions of A2 and A3 with ENR under similar conditions have demonstrated that the predominant reaction with epoxide groups was due to the carboxylic groups from the fact that A2 could form higher amount of crosslinkages than A3, which has lower carboxylic content similar to A1. V C 2010 Wiley Periodicals, Inc. J Appl Polym Sci 120: [1503][1504][1505][1506][1507][1508][1509] 2011

Phenytoin-loaded alkyd nanoemulsions were prepared spontaneously using the phase inversion method from a mixture of novel biosourced alkyds and Tween 80 surfactant. Exposure of human adult keratinocytes (HaCaT cells) for 48 h to alkyd nanoemulsions producing phenytoin concentrations of 3.125-200 μg/mL resulted in relative cell viability readings using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide of 100% confirming nontoxicity and suggesting cell proliferation activity. Phenytoin-loaded alkyd nanoemulsions generally resulted in higher mean cell viability compared with equivalent concentration of phenytoin solutions, suggesting that the nanoemulsions provided a controlled-release property that maintained the optimum phenytoin level for keratinocyte growth. HaCaT cell proliferation, measured by 5-bromo-2-deoxyuridine uptake, was found to increase following exposure to increasing phenytoin concentration from 25 to 50 μg/mL in solution or encapsulated in nanoemulsions but declined at a drug concentration of 100 μg/mL. An in vitro cell monolayer wound scratch assay revealed that phenytoin solution or nanoemulsions producing 50 μg/mL phenytoin concentration resulted in 75%-82% "scratch closure" after 36 h, similar to medium containing 10% fetal bovine serum as a cell growth promoter. These findings indicate that phenytoin-loaded alkyd nanoemulsions show potential for promoting topical wound healing through enhanced proliferation of epidermal cells.

Novel alkyds of short, medium, and long oil length were synthesized using a two‐stage alcoholysis‐polyesterification method from bio‐sourced starting materials. Alcoholysis reaction mixtures of palm kernel oil and glycerol underwent transesterification to convert triglycerides to monoglycerides within 3 h. Kinetic studies showed that the polyesterification reaction rates obeyed second order kinetics up to 15 min, followed by chain branching and crosslinking. The alkyd chemical structure was confirmed by nuclear magnetic resonance and Fourier Transform infrared spectroscopy. Gel permeation chromatography revealed that the average molecular weight of the alkyds was confined to <2,000 Da which is advantageous for the production of nanoscale drug carriers. Differential scanning calorimetry showed that the alkyds possess low glass transition temperatures within a very narrow range of −49.3°C–−52.7°C. Thermogravimetric analysis revealed good thermal stability with alkyd degradation occurring above 200°C. Cell viability assay confirmed that the alkyds were non‐toxic to 3T3 mouse fibroblasts following exposure of cell cultures for 24 h to solutions of concentration ranging from 3 to 100 μg/mL. These findings highly recommend consideration of the novel, bio‐sourced alkyds for pharmaceuticals manufacture and controlling drug delivery. Practical applications: A family of short, medium, and long oil length alkyds was synthesized as novel biomaterials from fully bio‐sourced and renewable starting materials. The alkyds are characterized by molecular weights below 2,000 Da, low Tg around −50°C and high thermal stability. The alkyds to exhibit favorable biocompatibility as demonstrated by non‐toxicity towards to 3T3 mouse fibroblasts in cell culture. Thus the novel bio‐sourced alkyds offer significant potential as excipients for pharmaceuticals manufacture and controlling drug delivery. Novel biocompatible palm oil‐based alkyds are investigated through synthesis reaction, kinetic study, and characterization tests. Alkyd synthesis involved two‐stage alcoholysis‐polyesterification reactions to produce short, medium, and long oil length alkyds. In the kinetic study of polyesterification reaction, water released was collected and acid value was determined with the results indicating high yield of alkyds with 97–98% of extent of polyesterification. The characterization of alkyds are carried out using spectroscopic, end group, thermal, and chromatographic analysis, plus biocompatible assay. The proposed chemical structure of the alkyd chain is determined from FTIR and NMR spectroscopy analysis. End group analysis indicated low acid groups but high hydroxyl numbers. Thermal analysis revealed the Tg ranged from −49.3°C to −52.7°C (DSC test) and thermal stability up to 200°C (TGA test). Average molecular weight is found to be less than 2,000 Da from GPC measurement or chromatographic analysis. All alkyds exhibited non‐toxic to 3T3 mouse fibroblast via biocompatible ‐ cell viability assay.