Encapsulation of polyketide colorants in chitosan and maltodextrin microparticles.

This study aimed to encapsulate Talaromyces amestolkiae colorants in maltodextrin and chitosan microparticles using the spraydrying technique and to evaluate the biopolymers' capacities to protect the fungal colorant against temperature (65 °C) and extreme pH (2.0 and 13.0). The compact microparticles exhibited smooth or indented surfaces with internal diameters ranging between 2.58-4.69 µm and ζ ~ -26 mV. The encapsulation efficiencies were 86 % and 56 % for chitosan and maltodextrin microparticles, respectively. The shifted endothermic peaks of the free colorants indicated their physical stabilization into microparticles. The encapsulated colorants retained most of their absorbance (compared to the 0 h) even after 25 days at 65 °C. Contrary, the free colorant presented almost no absorbance after 1 day under the same conditions. Colorants in chitosan and maltodextrin matrices also partially maintained their colorimetric and fluorometric properties at acidic pH. However, only maltodextrin improved the resistance of the red colorant to alkaline environments. For the first time, the potential of polysaccharide-based microparticles to preserve polyketide colorants was demonstrated using 3D fluorescence. Therefore, this study demonstrated an alternative in developing functional products with natural color additives.

Insect residues as an alternative and promising source for the extraction of chitin and chitosan.

This work aimed to obtain and characterize chitin and chitosan extracted from the rearing residues of Tenebrio molitor, Zophobas morio, and Blaptica dubia insects in different growth stages in the same rearing cycles chitin and chitosan yielded 11.21 %-20.89 % and 6.26 %-7.07 %, respectively. The deacetylation degrees of chitosan ranged from 75.75 %-89.21 %, and the solubilities from 69.88 %-94.39 %. Infrared spectroscopy corroborated the acquisition of chitin and chitosan and can be used as a semi-quantitative technique for determining the degree of chitosan deacetylation. The X-ray diffraction profiles revealed the presence of α-chitin, and the relative crystalline indices ranged from 65.9 %-89.2 %. Typical TG profiles with two thermal events are observed for chitin and chitosan samples with different residue contents from the extraction procedure. The chitosan solutions exhibited pseudoplastic behavior, with apparent viscosities ranging from 195.96 to 249.86 mPa.s. The characterization results of the biopolymers extracted from insect residues were similar to those obtained from conventional sources. The growth stage influenced the chitin yield and crystallinity index. The results of this study reinforce the feasibility of using alternative sources of chitin and chitosan, providing the use of waste from insect farms and contributing to sustainability and a circular economy.

Exploring the permeability of Amphotericin B trough serum albumin dispersions and lipid nanocarriers for oral delivery.

Amphotericin B (AmB) is a potent polyenic antifungal agent with leishmanicidal activity. Due to its low solubility and permeability in the gastrointestinal tract, AmB is usually administered intravenously. In this context, various approaches have been used to try to improve these properties. Some of the systems developed have shown proven successful, but there is still a lack of knowledge about the pathways AmB takes after oral administration. Therefore, the aim of this work was not only to obtain aqueous dispersions containing AmB at different aggregation states, but also to entrap this molecule in nanocarriers, and evaluate the influence of these conditions on the jejunal permeability of AmB. To observe the aggregation states of AmB, physicochemical characterization of AmB-albumin complexes and AmB-loaded formulations was performed. Different degrees of AmB aggregation states were obtained. Thus, permeability tests were performed in the Ussing chamber and a decrease in AmB concentration in the donor compartment was observed. Electrophysiological measurements showed different responses depending on the AmB formulation. In conclusion, although control of the AmB aggregation state was observed by physicochemical characterization, this approach does not seem to have a sufficient effect on AmB permeability, but on its toxicity. For a complete understanding of AmB-loaded nanocarriers, other pathways, such as lymphatic absorption, should also be investigated.

Effect of Addition of Cross-Linked Starch on the Properties of Degraded PBAT Poly(butylene adipate-co-terephthalate) Films.

This work aimed to evaluate the properties of butylene adipate-co-terephthalate (PBAT) degraded after 1800 days of storage (DPBAT) by preparing blends (films) with crosslinked starch (Cm) through extrusion and thermocompression. Different ratios of DPBAT:Cm (70:30, 60:40, and 50:50 m/m) were prepared. The incorporation of Cm into DPBAT significantly changed the properties of the films by making them stiffer (increasing Young's modulus by up to 50%) and increasing the thermal resistance of DPBAT. The presence of crosslinked starch in the films made them less hydrophobic (with decreased contact angle and increased moisture content), but these parameters did not vary linearly with changes in the content of crosslinked starch in the blend (DPBAT:Cm). The microscopic images show an inhomogeneous distribution of Cm granules in the DPBAT matrix. Thus, the films prepared with PBAT show a significant decrease in their mechanical parameters and heat resistance after long-term storage. However, the preparation of blends of degraded DPBAT with crosslinked starch promoted changes in the properties of the films prepared by thermocompression, which could be useful for disposable packaging.

Alpha-Lipoic Acid as an Antioxidant Strategy for Managing Neuropathic Pain.

Neuropathic pain (NP) is the most prevalent and debilitating form of chronic pain, caused by injuries or diseases of the somatosensory system. Since current first-line treatments only provide poor symptomatic relief, the search for new therapeutic strategies for managing NP is an active field of investigation. Multiple mechanisms contribute to the genesis and maintenance of NP, including damage caused by oxidative stress. The naturally occurring antioxidant alpha-lipoic acid (ALA) is a promising therapeutic agent for the management of NP. Several pre-clinical in vitro and in vivo studies as well as clinical trials demonstrate the analgesic potential of ALA in the management of NP. The beneficial biological activities of ALA are reflected in the various patents for the development of ALA-based innovative products. This review demonstrates the therapeutic potential of ALA in the management of NP by discussing its analgesic effects by multiple antioxidant mechanisms as well as the use of patented ALA-based products and how technological approaches have been applied to enhance ALA's pharmacological properties.

Chemical and Pharmacological Properties of Decoquinate: A Review of Its Pharmaceutical Potential and Future Perspectives.

Decoquinate (DQ) is an antimicrobial agent commonly used as a feed additive for birds for human consumption. Its use as an additive is well established, but DQ has the potential for therapy as an antimicrobial drug for veterinary treatment and its optimized derivatives and/or formulations, mainly nanoformulations, have antimicrobial activity against pathogens that infect humans. However, DQ has a high partition coefficient and low solubility in aqueous fluids, and these biopharmaceutical properties have limited its use in humans. In this review, we highlight the antimicrobial activity and pharmacokinetic properties of DQ and highlight the solutions currently under investigation to overcome these drawbacks. A literature search was conducted focusing on the use of decoquinate against various infectious diseases in humans and animals. The search was conducted in several databases, including scientific and patent databases. Pharmaceutical nanotechnology and medicinal chemistry are the tools of choice to achieve human applications, and most of these applications have been able to improve the biopharmaceutical properties and pharmacokinetic profile of DQ. Based on the results presented here, DQ prototypes could be tested in clinical trials for human application in the coming years.

Development of diethylcarbamazine-loaded poly(caprolactone) nanoparticles for anti-inflammatory purpose: Preparation and characterization

Abstract Diethylcarbamazine-loaded nanoparticles were previously evaluated for their anti-inflammatory activity. However, little is known regarding their physicochemical properties. Thus, the purpose of this study was to physiochemically characterize diethylcarbamazine-loaded poly(caprolactone) nanoparticles and evaluate their in vitro cytotoxicity. All formulations were prepared using the double-emulsion method. The average particle size was in the ranged between 298 and 364 nm and the polydispersity indexes were below 0.3. The zeta potential values were marginally negative, which may be related to drug loading, as higher loading led to an increase in the modulus of the zeta potential values. Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction (XRD) analysis did not reveal any chemical interactions between the chemicals used and the absence of drug in crystalline form on the nanoparticle surfaces. The in vitro drug release study revealed a concentration-dependent release from the nanoparticles into the medium. The in vitro cytotoxicity assay demonstrated the biocompatibility of the blank and loaded nanoparticles. Hence, all formulations presented good physicochemical and safety properties, corroborating the in vivo anti-inflammatory activity, previously reported by our group.

Starch chemical modifications applied to drug delivery systems: From fundamentals to FDA-approved raw materials.

Starch derivatives are versatile compounds that are widely used in the pharmaceutical industry. This article reviews the advances in the research on hydrophilic and hydrophobic starch derivatives used to develop drug delivery systems over the last ten years, specifically microparticles, nanoparticles, nanocrystals, hydrogels, and scaffolds using these materials. The fundamentals of drug delivery systems, regulatory aspects, and chemical modifications are also discussed, along with the synthesis of starch derivatives via oxidation, etherification, acid hydrolysis, esterification, and cross-linking. The chemical modification of starch as a means to overcome the challenges in obtaining solid dosage forms is also reviewed. In particular, dialdehyde starches are potential derivatives for direct drug attachment; carboxymethyl starches are used for drug encapsulation and release, giving rise to pH-sensitive devices through electrostatic interactions; and starch nanocrystals have high potential as hydrogel fillers to improve mechanical properties and control drug release through hydrophilic interactions. Starch esterification with alginate and acidic drugs could be very useful for site-specific, controlled release. Starch cross-linking with other biopolymers such as xanthan gum is promising for obtaining novel polyelectrolyte hydrogels with improved functional properties. Surface modification of starch nanoparticles by cross-linking and esterification reactions is a potential approach to obtain novel, smart solid dosages.

A Functional Wound Dressing as a Potential Treatment for Cutaneous Leishmaniasis.

Cutaneous leishmaniasis (CL) is a parasitic disease characterized by progressive skin sores. Currently, treatments for CL are limited to parenteral administration of the drug, which presents severe adverse effects and low cure rates. Therefore, this study aimed to develop poly(vinyl-alcohol) (PVA) hydrogels containing Amphotericin B (AmB) intended for topical treatment of CL. Hydrogels were evaluated in vitro for their potential to eliminate promastigote forms of Leishmania spp., to prevent secondary infections, to maintain appropriate healing conditions, and to offer suitable biocompatibility. AmB was incorporated into the system in its non-crystalline state, allowing it to swell more and faster than the system without the drug. Furthermore, the AmB release profile showed a continuous and controlled behavior following Higuchi´s kinetic model. AmB-loaded-PVA-hydrogels (PVA-AmB) also showed efficient antifungal and leishmanicidal activity, no cytotoxic potential for VERO cells, microbial impermeability and water vapor permeability compatible with the healthy skin's physiological needs. Indeed, these results revealed the potential of PVA-AmB to prevent secondary infections and to maintain a favorable environment for the healing process. Hence, these results suggest that PVA-AmB could be a suitable and efficient new therapeutic approach for the topical treatment of CL.

Understanding Drug Release Data through Thermodynamic Analysis.

Understanding the factors that can modify the drug release profile of a drug from a Drug-Delivery-System (DDS) is a mandatory step to determine the effectiveness of new therapies. The aim of this study was to assess the Amphotericin-B (AmB) kinetic release profiles from polymeric systems with different compositions and geometries and to correlate these profiles with the thermodynamic parameters through mathematical modeling. Film casting and electrospinning techniques were used to compare behavior of films and fibers, respectively. Release profiles from the DDSs were performed, and the mathematical modeling of the data was carried out. Activation energy, enthalpy, entropy and Gibbs free energy of the drug release process were determined. AmB release profiles showed that the relationship to overcome the enthalpic barrier was PVA-fiber > PVA-film > PLA-fiber > PLA-film. Drug release kinetics from the fibers and the films were better fitted on the Peppas-Sahlin and Higuchi models, respectively. The thermodynamic parameters corroborate these findings, revealing that the AmB release from the evaluated systems was an endothermic and non-spontaneous process. Thermodynamic parameters can be used to explain the drug kinetic release profiles. Such an approach is of utmost importance for DDS containing insoluble compounds, such as AmB, which is associated with an erratic bioavailability.

Preparation and characterization of safe microparticles based on xylan.

This work describes the preparation and evaluation of safe xylan-based microparticles prepared by cross-linking polymerization using sodium trimetaphosphate. The resulting microparticles were evaluated for morphology, particle size, polymer-cross-link agent interaction, and in vitro toxicity. The microparticles showed narrow monodisperse size distributions with their mean sizes being between 3.5 and 12.5 µm in dried state. FT-IR analyzes confirmed the interaction between sodium trimetaphosphate and xylan during the cross-linking process with formation of phosphate ester bonds. Additionally, the X-ray diffraction patterns and FT-IR analyzes suggested that little or no cross-linking agent remained inside the microparticles. Furthermore, the in-vitro studies using Artemia salina and human erythrocytes revealed that the microparticles are not toxic. Therefore, the overall results suggest that these xylan microparticles can be used as a platform for new drug delivery system.

Freeze-drying of emulsified systems: A review.

Colloidal systems such as emulsions, microemulsions and nanoemulsions are able to transport active molecules, enhance their solubility and stability and minimize their side effects. However, since they are dispersions with an aqueous continuous phase they have some disadvantages such as the risk of microbiological contamination, degradation by hydrolysis, physico-chemical instability and loss of pharmacological activity of the drug. Freeze drying, in which the water is removed from the preparation by sublimation under vacuum, has been suggested as a means to resolve these problems. Lyophilized products are very stable and are easy to transport and store. However, there is very little information in the literature about the application of this technique to emulsified systems. The aim of this review is to evaluate the lyophilization process as a tool for increasing the shelf life of emulsified systems such as emulsions, microemulsions and nanoemulsions. In addition, the mechanism of cryoprotection and the techniques that can be used to characterize the freeze-dried systems are discussed.

Producing xylan/Eudragit® S100-based microparticles by chemical and physico-mechanical approaches as carriers for 5-aminosalicylic acid.

Xylan is a biopolymer found in a variety of cell wall plants. Eudragit® S-100 (ES100), a pH-dependent polymer, is used as a coating material in gastroresistant delivery systems. In this study, microparticles based on both polymers were produced by interfacial cross-linking polymerisation and/or spray-drying technique in order to investigate feasibility and stability of the systems. Size and morphology of the microparticles were characterised by optical and SEM while FT-IR, thermal analysis (TG/DTA), and X-ray diffraction (XRD) evaluated the drug-polymer interactions and the thermal behaviour of the systems. FT-IR confirmed the absence of chemical interaction between the polymers. TG/DTA analysis showed a higher stability for spray-dried microparticles and XRD data proved the amorphous feature of both carriers. The results reveal that xylan/ES100 microparticles can be produced by chemical or physico-mechanical ways, the latter being the best option due to the lack of toxic cross-linking agents and easy scale-up.

Xylan from corn cobs, a promising polymer for drug delivery: production and characterization.

Although many authors have reported several beneficial effects ascribed to xylan, such as inhibitory action on mutagenicity activity, antiphlogistic effects, and mitogenic and comitogenic activities, few papers have investigated a systematic study on the technological properties of this polymer. The aim of the present work was to evaluate xylan as a promise raw material for the pharmaceutical industry. The water-insoluble xylan samples were extracted from corn cobs following several steps. The obtained powered sample was analyzed by infrared and RMN spectroscopy, and characterized regarding their particle size, bulk and tap densities, compressibility index, compactability, Hausner ratio, and angle of repose. According to the results, infrared and RMN spectroscopy were shown to be able to evaluate the xylan structural conformation and composition, respectively. In addition, rheological data demonstrated that xylan powder obtained from corn cobs may be characterized as a material with low density and very cohesive flow properties.