Didanosine-loaded chitosan microspheres: optimization of fabrication process

Didanosine (ddI) is an important drug in the AIDS therapy. However, to overcome the instability of ddI in acid medium, the tablets have a large amount of buffer that can lead to side effects such as diarrhea and kidney problems. Microencapsulation of ddI can reduce the excessive use of buffers. In this work we used the ionotropic gelation technique in the preparation of chitosan microspheres. The microspheres were characterized according to the incorporation efficiency, loading capacity, degree of swelling, permeability and morphology. The best results were obtained for 10 g of chitosan/g of sodium tripolyphosphate. Subsequently, changes were carried out in the agitation system in order to optimize it. Such changes were able to improve the incorporation efficiency as well as reduce the energy consumption of the system.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Evaluation of physical properties of chitosan active membrane loaded with phytotherapic extract and silver sulfadiazine

Polymeric membranes have been used as wound dressings for burns and healing wounds. Healing properties, anti-inflammatory and antibiotic in such membranes can be induced and/or made possible with the incorporation of bioactive as phytotherapic extract. In this work chitosan membranes were produced incorporating a commercial phytotherapic extract. The membranes were prepared by casting a chitosan solution and phytotherapic extract in a Petri dish and dried for 24 hs. We studied the effect of the concentration of the phytotherapic extract (PE) on membranes properties. Additionally, membranes were prepared with silver sulfadiazine (SS), an antibiotic ointment used for burns. The membranes were characterized for thickness, water vapor permeability rate, water uptake capacity, erosion degree and infrared spectroscopy. The results showed that the incorporation of low concentrations of extract promotes changes in the water uptake capacity and erosion degree, while high concentrations promote changes in the water vapor permeability.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Genotoxicity assessment of metal-based nanocomposites applied in drug delivery

Nanocomposites as drug delivery systems (e.g., metal nanoparticles) are being exploited for several applications in the biomedical field, from therapeutics to diagnostics. Green nanocomposites stand for nanoparticles of biocompatible, biodegradable and non-toxic profiles. When using metal nanoparticles for drug delivery, the question of how hazardous these virus-sized particles can be is posed, due to their nanometer size range with enhanced reactivity compared to their respective bulk counterparts. These structures exhibit a high risk of being internalized by cells and interacting with the genetic material, with the possibility of inducing DNA damage. The Comet Assay, or Single-Cell Gel Electrophoresis (SCGE), stands out for its capacity to detect DNA strand breaks in eukaryotic cells. It has huge potential in the genotoxicity assessment of nanoparticles and respective cells interactions. In this review, the Comet assay is described, discussing several examples of its application in the genotoxicity evaluation of nanoparticles commonly administered in a set of routes (oral, skin, inhaled, ocular and parenteral administration). In the nanoparticles boom era, where guidelines for their evaluation are still very limited, it is urgent to ensure their safety, alongside their quality and efficacy. Comet assay or SCGE can be considered an essential tool and a reliable source to achieve a better nanotoxicology assessment of metal nanoparticles used in drug delivery.This work was funded by the Portuguese Science and Technology Foundation (FCT) from the Ministry of Science and Technology (MCTES), through the projects UIDB/04469/2020 (CEB strategic fund) and UIDB/04033/2020 (CITAB), co-funded by European Funds (PRODER/COMPETE) and FEDER, under the Partnership Agreement PT2020. The work was also supported by the National Science Centre within the MINIATURA 4 for single research activity (grant No: 2020/04/X/ST5/00789) and by the START 2021 Program of the Foundation for Polish Science (FNP) granted to Dr. Aleksandra Zielińskainfo:eu-repo/semantics/publishedVersio

Effect of chitosan and Aloe Vera extract concentrations on the physicochemical properties of chitosan biofilms

Chitosan films have been extensively studied as dressings in formulations for the treatment of chronic wounds. The incorporation of aloe vera (Aloe barbadensis Miller) into chitosan dressings could potentialize the healing process since aloe vera shows several pharmacological activities. This work aimed to evaluate the effect of aloe vera and chitosan concentrations on the physicochemical properties of the developed films. The films were obtained by casting technique and characterized with respect to their color parameters, morphology, barrier and mechanical properties, and thermal analysis. Results showed that the presence of aloe vera modified the films color parameters, changed barrier properties, increased fluid handling capacity (FHC), and decreased water-vapor permeability (WVP). The reduced elongation at break resulted in more rigid films. Aloe vera concentration did not significantly change film properties, but the presence of this gel increased the films stability at temperatures below 200 °C, showing similar behavior as chitosan films above 400 °C. The results suggest a crosslinking/complexation between chitosan and aloe vera, which combine appropriate physicochemical properties for application as wound dressing materials.This work was supported by São Paulo Research Foundation (FAPESP) (2010/17.721-4), Portuguese Science and Technology Foundation (FCT) through the projects M-ERA-NET/0004/2015 (PAIRED) and UIDB/04469/2020 (strategic fund) funded by national funds, and co-financed Education (FCT/MEC) from national funds and FEDER, under the Partnership Agreement PT202info:eu-repo/semantics/publishedVersio

Applications of natural, semi-synthetic, and synthetic polymers in cosmetic formulations

Cosmetics composed of synthetic and/or semi-synthetic polymers, associated or not with natural polymers, exhibit a dashing design, with thermal and chemo-sensitive properties. Cosmetic polymers are also used for the preparation of nanoparticles for the delivery of, e.g., fragrances, with the purpose to modify their release profile and also reducing the risk of evaporation. Besides, other cosmetically active nutrients, dermal permeation enhancers, have also been loaded into nanoparticles to improve their bioactivities on the skin. The use of natural polymers in cosmetic formulations is of particular relevance because of their biocompatible, safe, and eco-friendly character. These formulations are highly attractive and marketable to consumers, and are suitable for a plethora of applications, including make-up, skin, and hair care, and as modifiers and stabilizers. In this review, natural synthetic, semi-synthetic, and synthetic polymers are discussed considering their properties for cosmetic applications. Their uses in conventional and novel formulations are also presented.This research was funded by Banco do Nordeste (FUNDECI 2017.0016), Coordenação Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado de Sergipe (FAPITEC)(PROCESSO: 88887.159533/2017-00), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq301964/2019-0, and Chamada CNPq nº01/2019) and by Portuguese Science and Technology Foundation, Ministryof Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the project reference UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020info:eu-repo/semantics/publishedVersio

Lipid-polymeric films: composition, production and applications in wound healing and skin repair

The use of lipids in the composition of polymeric-based films for topical administration of bioactive ingredients is a recent research topic; while few products are commercially available, films containing lipids represent a strategic area for the development of new products. Some lipids are usually used in polymeric-based film formulations due to their plasticizing action, with a view to improving the mechanical properties of these films. On the other hand, many lipids have healing, antimicrobial, anti-inflammatory, anti-aging properties, among others, that make them even more interesting for application in the medical-pharmaceutical field. This manuscript discusses the production methods of these films both on a laboratory and at industrial scales, the properties of the developed biopolymers, and their advantages for the development of dermatologic and cosmetic products.This research was funded by the Portuguese Science and Technology Foundation (FCT/MCT) and European Funds (PRODER/COMPETE), under the project reference UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Anti-tumor efficiency of Perillylalcohol/β-Cyclodextrin inclusion complexes in a sarcoma S180-induced mice model

The low solubility and high volatility of perillyl alcohol (POH) compromise its bioavailability and potential use as chemotherapeutic drug. In this work, we have evaluated the anticancer activity of POH complexed with -cyclodextrin (-CD) using three complexation approaches. Molecular docking suggests the hydrogen-bond between POH and -cyclodextrin in molar proportion was 1:1. Thermal analysis and Fourier-transform infrared spectroscopy (FTIR) confirmed that the POH was enclosed in the -CD cavity. Also, there was a significant reduction of particle size thereof, indicating a modification of the -cyclodextrin crystals. The complexes were tested against human L929 fibroblasts after 24 h of incubation showing no signs of cytotoxicity. Concerning the histopathological results, the treatment with POH/-CD at a dose of 50 mg/kg promoted approximately 60% inhibition of tumor growth in a sarcoma S180-induced mice model and the reduction of nuclear immunoexpression of the Ki67 antigen compared to the control group. Obtained data suggest a significant reduction of cycling cells and tumor proliferation. Our results confirm that complexation of POH/-CD not only solves the problem related to the volatility of the monoterpene but also increases its efficiency as an antitumor agent.This work was supported by the Banco do Nordeste (grant FUNDECI/2016.0015), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe (Fapitec) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Eliana B. Souto would like to acknowledge the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the project UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

β-cyclodextrin/isopentyl caffeate inclusion complex: synthesis, characterization and antileishmanial activity

Isopentyl caffeate (ICaf) is a bioactive ester widely distributed in nature. Our patented work has shown promising results of this molecule against Leishmania. However, ICaf shows poor solubility, which limits its usage in clinical settings. In this work, we have proposed the development of an inclusion complex of ICaf in -cyclodextrin (-CD), with the aim to improve the drug solubility, and thus, its bioavailability. The inclusion complex (ICaf:-CD) was developed applying three distinct methods, i.e., physical mixture (PM), kneading (KN) or co-evaporation (CO) in different molar proportions (0.25:1, 1:1 and 2:1). Characterization of the complexes was carried out by thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and molecular docking. The ICaf:-CD complex in a molar ratio of 1:1 obtained by CO showed the best complexation and, therefore, was selected for further analysis. Solubility assay showed a marked improvement in the ICaf:-CD (CO, 1:1) solubility profile when compared to the pure ICaf compound. Cell proliferation assay using ICaf:-CD complex showed an IC50 of 3.8 and 2.7 µg/mL against L. amazonesis and L. chagasi promastigotes, respectively. These results demonstrate the great potential of the inclusion complex to improve the treatment options for visceral and cutaneous leishmaniases.This research was funded by Banco do Nordeste (grant FUNDECI/2016.0015), Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES) and Fundação de Ámparo à Pesquisa do Estado de Sergipe (FAPITEC) (PROCESSO: 88887.159533/2017-00 extração, encapsulação e caracterização de bioativos para o interesse biotecnologico). Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 301964/2019-0 Chamada 06/2019, and Chamada CNPq nº 01/2019) and from the Portuguese Science and Technology Foundation (FCT) project UIDB/04469/2020 (strategic fund).info:eu-repo/semantics/publishedVersio

Adsorption Isotherms of Mucin on Granules Containing Chitosan Microspheres

The effect of the excipients used for the preparation of granules containing chitosan microspheres on the adsorption of the muco-polysaccharide mucin was studied. Adsorption isotherms at 37°C were obtained as one strategy for the in vitro evaluation of the muco-adhesive properties of granules carrying drugs. The microspheres were prepared via an ionotropic gelation technique using sodium tripolyphosphate as the cross-linking agent. The resulting microspheres were dried at 40°C until a water content of 75% was achieved and the subsequent extrusion/spherulation process carried out using different excipients, i.e. unmodified chitosan, pre-gelated starch or carboxymethylcellulose. The Langmuir adsorption equation gave a good fit to the experimental data. Mucin exhibited the best affinity to granules containing chitosan as the excipient. Such granules also appeared to have the best muco-adhesive properties