Pectin hydrogels for controlled drug release: Recent developments and future prospects.

Pectin hydrogels have emerged as a highly promising medium for the controlled release of pharmaceuticals in the dynamic field of drug delivery. The present review sheds light on the broad range of applications and potential of pectin-based hydrogels in pharmaceutical formulations. Pectin, as a biopolymer, is a versatile candidate for various drug delivery systems because of its wide range of properties and characteristics. The information provided on formulation strategies and crosslinking techniques provides researchers with tools to improve drug entrapment and controlled release. Furthermore, this review provides a more in-depth understanding of the complex factors influencing drug release from pectin hydrogels, such as the impact of environmental conditions and drug-specific characteristics. Pectin hydrogels demonstrate adaptability across diverse domains, ranging from applications in oral and transdermal drug delivery to contributions in wound healing, tissue engineering, and ongoing clinical trials. While standardization and regulatory compliance remain significant challenges, the future of pectin hydrogels appears to be bright, opening up new possibilities for advanced drug delivery systems.

Multi-target drug with potential applications: violacein in the spotlight.

The aim of the current review is to address updated research on a natural pigment called violacein, with emphasis on its production, biological activity and applications. New information about violacein's action mechanisms as antitumor agent and about its synergistic action in drug delivery systems has brought new alternatives for anticancer therapy. Thus, violacein is introduced as reliable drug capable of overcoming at least three cancer hallmarks, namely: proliferative signaling, cell death resistance and metastasis. In addition, antimicrobial effects on several microorganisms affecting humans and other animals turn violacein into an attractive drug to combat resistant pathogens. Emphasis is given to effects of violacein combined with different agents, such as antibiotics, anticancer agents and nanoparticles. Although violacein is well-known for many decades, it remains an attractive compound. Thus, research groups have been making continuous effort to help improving its production in recent years, which can surely enable its pharmaceutical and chemical application as multi-task compound, even in the cosmetics and food industries.

Physiological and morphological responses of green microalgae Chlorella vulgaris to silver nanoparticles.

The toxic effects of silver nanoparticles (AgNPs) on the physiology and morphology of the green microalga Chlorella vulgaris were studied. AgNPs were characterized by particle size distribution, ζ potential measurement, and atomic force microscopy (AFM). Chlorella vulgaris was exposed to 90-1440 µg/L of AgNPs range in Bold's Basal Medium for 96 h. The inhibition of algae growth rate and changes in the concentrations of chlorophyll-a, chlorophyll-b, pheophytin, and carotenoids was determined at the beginning and end of the trial. Cell diameter and volume, carbohydrate, total lipids, and protein content were also determined. Our data strongly suggest that the toxic effects of the AgNPs resulted in concentration and time-dependent. AgNPs altered C. vulgaris growth kinetics and cell metabolism expressed in photosynthetic pigments and biochemical composition. Our study confirmed the cytotoxicity of AgNPs through the algal growth inhibition with an EC50 value of 110 µg/L. Also, changes of chlorophyll-a, chlorophyll-b, pheophytin, and carotenoids concentrations were observed associated with a color shift from green to pale brown of algae cultures exposed to AgNPs for 96 h. Furthermore, algae cell concentration, diameter, and volume, plus total lipid, protein, and carbohydrates contents in the presence of AgNPs, were significantly altered compared to untreated cells. In synthesis, this study highlighted AgNPs toxic effects on morphological and physiological traits of C. vulgaris and warns about possible impacts on energy flow and aquatic food web structure, and on the transfer efficiency of energy to higher trophic levels.

Simple colorimetric method to determine the in vitro antioxidant activity of different monoterpenes.

The development of simple, fast and reproducible techniques that provide information about the antioxidant activity (AA) of different compounds is essential to screen and discover new molecules with potential applications in the therapeutic, cosmetic, toxicological and food fields. Here, a novel and simple colorimetric method ("BCB assay") is proposed for measuring the AA of chemical compounds by protection of the reporter dye Brilliant Cresyl Blue (BCB) from loss of color due to oxidation by hypochlorite (a physiological oxidant). The decay in BCB blue color (λmax = 634 nm) in the presence of hypochlorite occurred in only 5 min and was used to track the AA of different molecules. Particularly, the AA of monoterpenes was demonstrated and used to quantify them at milimolar concentrations. Natural antioxidants like vitamins C and E, resveratrol, dithiothreitol, N-actyl-l-cysteine and glutathione were used as controls to validate the assay. Linalool, geraniol and 1,8-cineole were tested and showed in vitro AA in a concentration-dependent manner. The monoterpene concentrations providing 50% protection against oxidation (AA50) were 2.3, 36.2 and 135.0 mM for linalool, geraniol and 1,8-cineole respectively, suggesting interesting AA. The method provides a useful, fast, simple and low-cost tool to determine the in vitro AA of different molecules.

Nanodevices for the immobilization of therapeutic enzymes.

Therapeutic enzymes are one of the most promising applications of this century in the field of pharmaceutics. Biocatalyst properties can be improved by enzyme immobilization on nano-objects, thereby increasing stability and reusability and also enhancing the targeting to specific tissues and cells. Therapeutic biocatalyst-nanodevice complexes will provide new tools for the diagnosis and treatment of old and newly emerging pathologies. Among the advantages of this approach are the wide span and diverse range of possible materials and biocatalysts that promise to make the matrix-enzyme combination a unique modality for therapeutic delivery. This review focuses on the most significant techniques and nanomaterials used for enzyme immobilization such as metallic superparamagnetic, silica, and polymeric and single-enzyme nanoparticles. Finally, a review of the application of these nanodevices to different pathologies and modes of administration is presented. In short, since therapeutic enzymes constitute a highly promising alternative for treating a variety of pathologies more effectively, this review is aimed at providing the comprehensive summary needed to understand and improve this burgeoning area.

Konjac glucomannan: A comprehensive review of its extraction, health benefits, and pharmaceutical applications.

Konjac glucomannan (KG) is a dietary fiber hydrocolloid derived from Amorphophallus konjac tubers and is widely utilized as a food additive and dietary supplement. As a health-conscious choice, purified KG, along with konjac flour and KG-infused diets, have gained widespread acceptance in Asian and European markets. An overview of the chemical composition and structure of KG is given in this review, along with thorough explanations of the processes used in its extraction, production, and purification. KG has been shown to promote health by reducing glucose, cholesterol, triglyceride levels, and blood pressure, thereby offering significant weight loss advantages. Furthermore, this review delves into the extensive health benefits and pharmaceutical applications of KG and its derivatives, emphasizing its prebiotic, anti-inflammatory, and antitumor activities. This study highlights how these natural polysaccharides can positively influence health, underscoring their potential in various biomedical applications.

Bacterial Cellulose-Based Materials as Dressings for Wound Healing.

Bacterial cellulose (BC) is produced by several microorganisms as extracellular structures and can be modified by various physicochemical and biological strategies to produce different cellulosic formats. The main advantages of BC for biomedical applications can be summarized thus: easy moldability, purification, and scalability; high biocompatibility; and straightforward tailoring. The presence of a high amount of free hydroxyl residues, linked with water and nanoporous morphology, makes BC polymer an ideal candidate for wound healing. In this frame, acute and chronic wounds, associated with prevalent pathologies, were addressed to find adequate therapeutic strategies. Hence, the main characteristics of different BC structures-such as membranes and films, fibrous and spheroidal, nanocrystals and nanofibers, and different BC blends, as well as recent advances in BC composites with alginate, collagen, chitosan, silk sericin, and some miscellaneous blends-are reported in detail. Moreover, the development of novel antimicrobial BC and drug delivery systems are discussed.

Quantitative determination of voriconazole by thionine reduction and its potential application in a pharmaceutical and clinical setting.

Voriconazole (VCZ) is a triazolic drug used to treat serious fungal infections and invasive mycosis and has also been more recently used as a generic antifungal treatment. However, VCZ therapies can cause undesirable side effects and doses must be carefully monitored before administration to avoid or reduce severe toxic effects. Analytical techniques used to quantify VCZ are mostly based on HPLC/UV and often associated with multiple technical steps as well as expensive equipment. The present work aimed to develop an accessible and affordable spectrophotometric technique in the visible range (λ = 514 nm) for the simple quantification of VCZ. The technique was based on VCZ-induced reduction of thionine (TH, red) to leucothionine (LTH, colorless) under alkaline conditions. The reaction showed a linear correlation over the range of 1.00 µg mL-1 to 60.00 µg mL-1 at room temperature, the limits of detection and quantification being 1.93 µg mL-1 and 6.45 µg mL-1, respectively. VCZ degradation products (DPs) according to 1H and 13C-NMR spectrometric determinations not only showed good agreement with the ones previously reported (DP1 and DP2 - T. M. Barbosa, G. A. Morris, M. Nilsson, R. Rittner and C. F. Tormena, RSC Adv., 2017, DOI: 10.1039/c7ra03822d), but also revealed a new degradation product (DP3). Mass spectrometry not only confirmed the presence of LTH as a result of the VCZ DP-induced TH reduction, but also revealed the formation of a novel and stable Schiff base as a reaction product between DP1 and LTH. The latter finding became significant as it stabilizes the reaction for quantification purposes, by hindering LTH ↔TH redox reversibility. This analytical method was then validated according to the ICH Q2 (R1) guidelines, and additionally, it could be demonstrated as applicable for the reliable VCZ quantification in commercially available tablets. Importantly, it also represents a useful tool for detecting toxic threshold concentrations in human plasma from VCZ-treated patients, alerting when these risky limits are exceeded. In this way, this technique independent from sophisticated equipment, highly qualifies as a low-cost, reproducible, trustable, and non-laborious alternative method for VCZ measurements from different matrices.

Pharmacological applications of nitric oxide-releasing biomaterials in human skin.

Nitric oxide (NO) is an important endogenous molecule that plays several roles in biological systems. NO is synthesized in human skin by three isoforms of nitric oxide synthase (NOS) and, depending on the produced NO concentration, it can actuate in wound healing, dermal vasodilation, or skin defense against different pathogens, for example. Besides being endogenously produced, NO-based pharmacological formulations have been developed for dermatological applications targeting diverse pathologies such as bacterial infection, wound healing, leishmaniasis, and even esthetic issues such as acne and skin aging. Recent strategies focus mainly on developing smart NO-releasing nanomaterials/biomaterials, as they enable a sustained and targeted NO release, promoting an improved therapeutic effect. This review aims to overview and discuss the main mechanisms of NO in human skin, the recent progress in the field of dermatological formulations containing NO, and their application in several skin diseases, highlighting promising advances and future perspectives in the field.

Design, Synthesis, Characterization, and Evaluation of the Anti-HT-29 Colorectal Cell Line Activity of Novel 8-Oxyquinolinate-Platinum(II)-Loaded Nanostructured Lipid Carriers Targeted with Riboflavin.

Colorectal cancer is occasionally called colon or rectal cancer, depending on where cancer begins to form, and is the second leading cause of cancer death among both men and women. The platinum-based [PtCl(8-O-quinolinate)(dmso)] (8-QO-Pt) compound has demonstrated encouraging anticancer activity. Three different systems of 8-QO-Pt-encapsulated nanostructured lipid carriers (NLCs) with riboflavin (RFV) were investigated. NLCs of myristyl myristate were synthesized by ultrasonication in the presence of RFV. RFV-decorated nanoparticles displayed a spherical shape and a narrow size dispersion in the range of 144-175 nm mean particle diameter. The 8-QO-Pt-loaded formulations of NLC/RFV with more than 70% encapsulation efficiency showed sustained in vitro release for 24 h. Cytotoxicity, cell uptake, and apoptosis were evaluated in the HT-29 human colorectal adenocarcinoma cell line. The results revealed that 8-QO-Pt-loaded formulations of NLC/RFV showed higher cytotoxicity than the free 8-QO-Pt compound at 5.0 µM. All three systems exhibited different levels of cellular internalization. Moreover, the hemotoxicity assay showed the safety profile of the formulations (less than 3.7%). Taken together, RFV-targeted NLC systems for drug delivery have been investigated for the first time in our study and the results are promising for the future of chemotherapy in colon cancer treatment.

3D Filaments Based on Polyhydroxy Butyrate-Micronized Bacterial Cellulose for Tissue Engineering Applications.

In this work, scaffolds based on poly(hydroxybutyrate) (PHB) and micronized bacterial cellulose (BC) were produced through 3D printing. Filaments for the printing were obtained by varying the percentage of micronized BC (0.25, 0.50, 1.00, and 2.00%) inserted in relation to the PHB matrix. Despite the varying concentrations of BC, the biocomposite filaments predominantly contained PHB functional groups, as Fourier transform infrared spectroscopy (FTIR) demonstrated. Thermogravimetric analyses (i.e., TG and DTG) of the filaments showed that the peak temperature (Tpeak) of PHB degradation decreased as the concentration of BC increased, with the lowest being 248 °C, referring to the biocomposite filament PHB/2.0% BC, which has the highest concentration of BC. Although there was a variation in the thermal behavior of the filaments, it was not significant enough to make printing impossible, considering that the PHB melting temperature was 170 °C. Biological assays indicated the non-cytotoxicity of scaffolds and the provision of cell anchorage sites. The results obtained in this research open up new paths for the application of this innovation in tissue engineering.

Nanostructured lipid carriers containing benznidazole: physicochemical, biopharmaceutical and cellular in vitro studies.

Chagas disease is a neglected endemic disease prevalent in Latin American countries, affecting around 8 million people. The first-line treatment, benznidazole (BNZ), is effective in the acute stage of the disease but has limited efficacy in the chronic stage, possibly because current treatment regimens do not eradicate transiently dormant Trypanosoma cruzi amastigotes. Nanostructured lipid carriers (NLC) appear to be a promising approach for delivering pharmaceutical active ingredients as they can have a positive impact on bioavailability by modifying the absorption, distribution, and elimination of the drug. In this study, BNZ was successfully loaded into nanocarriers composed of myristyl myristate/Crodamol oil/poloxamer 188 prepared by ultrasonication. A stable NLC formulation was obtained, with ≈80% encapsulation efficiency (%EE) and a biphasic drug release profile with an initial burst release followed by a prolonged phase. The hydrodynamic average diameter and zeta potential of NLC obtained by dynamic light scattering were approximately 150 nm and -13 mV, respectively, while spherical and well-distributed nanoparticles were observed by transmission electron microscopy. Fourier-transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and small-angle X-ray scattering analyses of the nanoparticles indicated that BNZ might be dispersed in the nanoparticle matrix in an amorphous state. The mean size, zeta potential, polydispersity index, and %EE of the formulation remained stable for at least six months. The hemolytic effect of the nanoparticles was insignificant compared to that of the positive lysis control. The nanoparticle formulation exhibited similar performance in vitro against T. cruzi compared to free BNZ. No formulation-related cytotoxic effects were observed on either Vero or CHO cells. Moreover, BNZ showed a 50% reduction in CHO cell viability at 125 µg/mL, whereas NLC-BNZ and non-loaded NLC did not exert a significant effect on cell viability at the same concentration. These results show potential for the development of new nanomedicines against T. cruzi.

Prodigiosin: a promising biomolecule with many potential biomedical applications.

Pigments are among the most fascinating molecules found in nature and used by human civilizations since the prehistoric ages. Although most of the bio-dyes reported in the literature were discovered around the eighties, the necessity to explore novel compounds for new biological applications has made them resurface as potential alternatives. Prodigiosin (PG) is an alkaloid red bio-dye produced by diverse microorganisms and composed of a linear tripyrrole chemical structure. PG emerges as a really interesting tool since it shows a wide spectrum of biological activities, such as antibacterial, antifungal, algicidal, anti-Chagas, anti-amoebic, antimalarial, anticancer, antiparasitic, antiviral, and/or immunosuppressive. However, PG vehiculation into different delivery systems has been proposed since possesses low bioavailability because of its high hydrophobic character (XLogP3-AA = 4.5). In the present review, the general aspects of the PG correlated with synthesis, production process, and biological activities are reported. Besides, some of the most relevant PG delivery systems described in the literature, as well as novel unexplored applications to potentiate its biological activity in biomedical applications, are proposed.

Enzymatic Active Release of Violacein Present in Nanostructured Lipid Carrier by Lipase Encapsulated in 3D-Bioprinted Chitosan-Hydroxypropyl Methylcellulose Matrix With Anticancer Activity.

Violacein (Viol) is a bacterial purple water-insoluble pigment synthesized by Chromobacterium violaceum and other microorganisms that display many beneficial therapeutic properties including anticancer activity. Viol was produced, purified in our laboratory, and encapsulated in a nanostructured lipid carrier (NLC). The NLC is composed of the solid lipid myristyl myristate, an oily lipid mixture composed of capric and caprylic acids, and the surfactant poloxamer P188. Dormant lipase from Rhizomucor miehei was incorporated into the NLC-Viol to develop an active release system. The NLC particle size determined by dynamic light scattering brings around 150 nm particle size and ζ≈ -9.0 mV with or without lipase, but the incorporation of lipase increase the PdI from 0.241 to 0.319 (≈32%). For scaffold development, a 2.5 hydroxypropyl methylcellulose/chitosan ratio was obtained after optimization of a composite for extrusion in a 3D-bioprinter developed and constructed in our laboratory. Final Viol encapsulation efficiency in the printings was over 90%. Kinetic release of the biodye at pH = 7.4 from the mesh containing NLC-lipase showed roughly 20% Viol fast release than without the enzyme. However, both Viol kinetic releases displayed similar profiles at pH = 5.0, where the lipase is inactive. The kinetic release of Viol from the NLC-matrices was modeled and the best correlation was found with the Korsmeyer-Peppas model (R2 = 0.95) with n < 0.5 suggesting a Fickian release of Viol from the matrices. Scanning Electron Microscope (SEM) images of the NLC-meshes showed significant differences before and after Viol's release. Also, the presence of lipase dramatically increased the gaps in the interchain mesh. XRD and Fourier Transform Infrared (FTIR) analyses of the NLC-meshes showed a decrease in the crystalline structure of the composites with the incorporation of the NLC, and the decrease of myristyl myristate in the mesh can be attributed to the lipase activity. TGA profiles of the NLC-meshes showed high thermal stability than the individual components. Cytotoxic studies in A549 and HCT-116 cancer cell lines revealed high anticancer activity of the matrix mediated by mucoadhesive chitosan, plus the biological synergistic activities of violacein and lipase.

Colloidal delivery of vitamin E into solid lipid nanoparticles as a potential complement for the adverse effects of anemia treatment.

Vitamin E (VitE) is one of the most important antioxidants and plays a key role in decreasing the inflammatory effects of oxidative stress caused by recurrent doses of iron administration in anemia treatment. However, VitE is poorly soluble in aqueous environments. Here, VitE encapsulation into solid lipid nanoparticles (SLN) composed of myristil myristate to improve its bioavailability was proposed. A 99.9 ± 0.1% encapsulation efficiency with a drug/lipid ratio of 500 µg/mg and 478 higher VitE solubility was obtained. The antioxidant properties of VitE after encapsulation were maintained. SLN-VitE showed a 228.2 nm mean diameter with low polidispersitivity (0.335), and negative Z potential (ζ ≈ -9.0 mV). The SLN were well-dispersed, displayed spherical and homogeneous morphology by TEM. A controlled release of VitE from SLN was found. The XRD and FTIR analyses revealed the presence of a nanostructured architecture of SLN after VitE incorporation. We probed the safety of SLN-VitE after contact with three in vitro cell models: erythrocytes, lymphocytes and HepG2 cells. The cell viability in presence of SLN, SLN-VitE, and their combinations with iron was not affected. The comet assay demonstrated that the DNA damage caused by iron administration was decrease in presence of SLN-VitE.

Nanostructured Lipid Carriers Loaded with Dexamethasone Prevent Inflammatory Responses in Primary Non-Parenchymal Liver Cells.

Liver inflammation represents a major clinical problem in a wide range of pathologies. Among the strategies to prevent liver failure, dexamethasone (DXM) has been widely used to suppress inflammatory responses. The use of nanocarriers for encapsulation and sustained release of glucocorticoids to liver cells could provide a solution to prevent severe side effects associated with systemic delivery as the conventional treatment regime. Here we describe a nanostructured lipid carrier developed to efficiently encapsulate and release DXM. This nano-formulation proved to be stable over time, did not interact in vitro with plasma opsonins, and was well tolerated by primary non-parenchymal liver cells (NPCs). Released DXM preserved its pharmacological activity, as evidenced by inducing robust anti-inflammatory responses in NPCs. Taken together, nanostructured lipid carriers may constitute a reliable platform for the delivery of DXM to treat pathologies associated with chronic liver inflammation.

Lipid, polymeric, inorganic-based drug delivery applications for platinum-based anticancer drugs.

The three main FDA-approved platinum drugs in chemotherapy such as carboplatin, cisplatin, and oxaliplatin are extensively applied in cancer treatments. Although the clinical applications of platinum-based drugs are extremely effective, their toxicity profile restricts their extensive application. Therefore, recent studies focus on developing new platinum drug formulations, expanding the therapeutic aspect. In this sense, recent advances in the development of novel drug delivery carriers will help with the increase of drug stability and biodisponibility, concomitantly with the reduction of drug efflux and undesirable secondary toxic effects of platinum compounds. The present review describes the state of the art of platinum drugs with their biological effects, pre- and clinical studies, and novel drug delivery nanodevices based on lipids, polymers, and inorganic.

Enzymes and biopolymers. The opportunity for the smart design of molecular delivery systems.

Enzymes exhibit a tremendous potential due to the catalytic activity in response to physiological conditions and specific microenvironments. Exploiting these properties in combination with the versatility of biopolymers, a fascinating field for the rational development of a new class of "smart" delivery systems for therapeutic molecules is proposed. Many strategies have been recently developed to produce matrices with the desirable properties of molecular release, and enzymes could be playing a relevant role in modify the chemical composition of the polymers, the porosity and surface area of the matrices and modulate the kinetic of controlled release. Enzyme based computational systems have appeared as a relevant complementary tool to design novel smart bioactive matrices for programmable drug delivery. The present review is reporting the recent advances and projections of smart biopolymeric matrices activated by enzymes for sustained release of therapeutic molecules, highlighting various applications in the area of advanced drug delivery.

Microbial production and recovery of hybrid biopolymers from wastes for industrial applications- a review.

Agro-industrial wastes to be a global concern since agriculture and industrial processes are growing exponentially with the fast increase of the world population. Biopolymers are complex molecules produced by living organisms, but also found in many wastes or derived from wastes. The main drawbacks for the use of polymers are the high costs of the polymer purification processes from waste and the scale-up in the case of biopolymer production by microorganisms. However, the use of biopolymers at industrial scale for the development of products with high added value, such as food or biomedical products, not only can compensate the primary costs of biopolymer production, but also improve local economies and environmental sustainability. The present review describes some of the most relevant aspects related to the synthesis of hybrid materials and nanocomposites based on biopolymers for the development of products with high-added value.

Binary Medical Nanofluids by Combination of Polymeric Eudragit Nanoparticles for Vehiculization of Tobramycin and Resveratrol: Antimicrobial, Hemotoxicity and Protein Corona Studies.

The development of smart nanoparticles (NPs) became a trend to enhance the delivery of drugs. In the present work, Tobramycin (TB), an aminoglycoside antibiotic that displays several undesirable side effects, has been encapsulated into cationic Eudragit®E100 (E100) NPs for the treatment of infections caused by Pseudomonas aeruginosa. Combination with neutral Eudragit®NE30D (NE30D) NPs containing resveratrol (RSV), a strong natural antioxidant, increased the antimicrobial activity of TB (75% higher than free TB). NPs were stabilized with 1.0% (w/v) poloxamer 188 (P188) or poloxamer 407 (P407) as surfactants. E100 NPs showed 83.3 ± 8.5%, and 70.1 ± 2.7 encapsulation efficiency (EE) of TB with P188 and P407 coatings, respectively. The presence of NPs was confirmed by DLS and TEM studies. TB was controlled released from NPs for 6 h. Hemotoxicity tests of NPs in the range of MIC values on human blood gave negative results. Analysis of Surface Plasmon Resonance verified that NE30D/P407/RSV does not interact with plasma proteins BSA, IgG or fibrinogen, besides E100/P188/TB interact with BSA, findings that are compatible with a negligible in vivo clearance of the nanovehicles. The obtained results show a potential binary fluid composed of two NPs to highly improve the effectiveness of conventional antibiotics.