Functional Hydrogels for Delivery of the Proteolytic Enzyme Serratiopeptidase.

Hydrogels are superior wound dressings because they can provide protection and hydration of the wound, as well as the controlled release of therapeutic substances to aid tissue regeneration and the healing process. Hydrogels obtained from natural precursors are preferred because of their low cost, biocompatibility, and biodegradability. We describe the synthesis of novel functional hydrogels based on two natural products-citric acid (CA) and pentane-1,2,5-triol (PT, a product from lignocellulose processing) and poly(ethylene glycol) (PEG-600)-via an environment friendly approach. The hydrogels were prepared via monomer crosslinking through a polycondensation reaction at an elevated temperature in the absence of any solvent. The reagents were blended at three different compositions with molar ratios of hydroxyl (from PT and PEG) to carboxyl (from CA) groups of 1:1, 1:1.4, and 1.4:1, respectively. The effect of the composition on the physicomechanical properties of materials was investigated. All hydrogels exhibited pH-sensitive behavior, while the swelling degree and elastic modulus were dependent on the composition of the polymer network. The proteolytic enzyme serratiopeptidase (SER) was loaded into a hydrogel via physical absorption as a model drug. The release profile of SER and the effects of the enzyme on healthy skin cells were assessed. The results showed that the hydrogel carrier could provide the complete release of the loaded enzyme.

Biorenewable Oxypropylated Pentane-1,2,5-triol as a Source for Incorporation in Rigid Polyurethane Foams.

In this study, as a product from the efficient Achmatowicz rearrangement and mild subsequent hydrogenation-reduction reactions of biorenewable C5 alcohols derived from lignocellulose, pentane-1,2,5-triol was successfully used after oxypropylation in the preparation of rigid polyurethane foams-one of the most important classes of polymeric materials. Despite the broad range of applications, the production of polyurethanes is still highly dependent on petrochemical materials considering the need of renewable raw materials and new process technologies for the production of polyol or isocyanate components as a key point for the sustainable development of polyurethane foams. The synthesized oxypropylated pentane-1,2,5-triol was analyzed using proton NMR spectroscopy, hydroxyl number, and viscosity, whereas the newly obtained foams incorporated with up to 30% biorenewable polyol were characterized using compressive stress, thermogravimetry, dynamic mechanical analysis, and scanning electron microscopy. The modified rigid polyurethanes showed better compressive strength (>400.0 kPa), a comparable thermal degradation range at 325-450 °C, and similar morphological properties to those of commercial polyurethane formulations.

Incorporation of Resveratrol in Polymeric Nanogel for Improvement of Its Protective Effects on Cellular and Microsomal Oxidative Stress Models.

Nanogels are attractive drug delivery systems that provide high loading capacity for drug molecules, improve their stability, and increase cellular uptake. Natural antioxidants, especially polyphenols such as resveratrol, are distinguished by low aqueous solubility, which hinders therapeutic activity. Thus, in the present study, resveratrol was incorporated into nanogel particles, aiming to improve its protective effects in vitro. The nanogel was prepared from natural substances via esterification of citric acid and pentane-1,2,5-triol. High encapsulation efficiency (94.5%) was achieved by applying the solvent evaporation method. Dynamic light scattering, atomic force microscopy, and transmission electron microscopy revealed that the resveratrol-loaded nanogel particles were spherical in shape with nanoscopic dimensions (220 nm). In vitro release tests showed that a complete release of resveratrol was achieved for 24 h, whereas at the same time the non-encapsulated drug was poorly dissolved. The protective effect of the encapsulated resveratrol against oxidative stress in fibroblast and neuroblastoma cells was significantly stronger compared to the non-encapsulated drug. Similarly, the protection in a model of iron/ascorbic acid-induced lipid peroxidation on rat liver and brain microsomes was higher with the encapsulated resveratrol. In conclusion, embedding resveratrol in this newly developed nanogel improved its biopharmaceutical properties and protective effects in oxidative stress models.

Ru-Catalyzed Isomerization of Achmatowicz Derivatives: A Sustainable Route to Biorenewables and Bioactive Lactones.

A Ru-catalyzed isomerization of Achmatowicz derivatives that opens unexplored routes to diversify the biogenic furanic platform is reported. The mechanistic insights of this formally redox-neutral intramolecular process were studied computationally and by deuterium labeling. The transformation proved to be a robust synthetic tool to achieve the synthesis of bioderived-monomers and a series of 4-keto-δ-valerolactones that further enabled the development of a flexible strategy for the synthesis of acetogenins. A concise and protective group-free asymmetric total synthesis of two natural products, namely, (S,S)-muricatacin and the (S,S)-L-factor, is also described.

Functional Nanogel from Natural Substances for Delivery of Doxorubicin.

Nanogels (NGs) have attracted great attention because of their outstanding biocompatibility, biodegradability, very low toxicity, flexibility, and softness. NGs are characterized with a low and nonspecific interaction with blood proteins, meaning that they do not induce any immunological responses in the body. Due to these properties, NGs are considered promising candidates for pharmaceutical and biomedical application. In this work, we introduce the development of novel functional nanogel obtained from two naturally based products-citric acid (CA) and pentane-1,2,5-triol (PT). The nanogel was synthesized by precipitation esterification reaction of CA and PT in tetrahydrofuran using N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide (EDC) and 4-(dimethylamino)pyridine (DMAP) catalyst system. Dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM) and atomic force microscopy (AFM) analyses revealed formation of spherical nanogel particles with a negative surface charge. Next, the nanogel was loaded with doxorubicin hydrochloride (DOX) by electrostatic interactions between carboxylic groups present in the nanogel and amino groups of DOX. The drug-loaded nanogel exhibited high encapsulation efficiency (EE~95%), and a bi-phasic release behavior. Embedding DOX into nanogel also stabilized the drug against photodegradation. The degradability of nanogel under acidic and neutral conditions with time was investigated as well.