Applied nanotechnologies in anticoagulant therapy: from anticoagulants to coagulation test performance of drug delivery systems

Heparin-based delivery systems have been explored to improve their therapeutic efficacy and to reduce toxicity for different administration routes. Regardless of the applied drug delivery system (DDS), the evaluation of anticoagulant performance is instrumental for the development of a suitable DDS. The understanding of the range of anticoagulant assays, together with their key applications and limitations, is essential both within the context of scientific research and for clinical usage. This review provides an overview of the current anticoagulant therapy and discusses the advantages and limitations of currently available anticoagulant assays. We also discuss studies involving low-molecular-weight heparin (LMWH)-based nanocarriers with emphasis on their anticoagulation performance. Conventional anticoagulants have been used for decades for the treatment of many diseases. Direct oral anticoagulants have overcome some limitations of heparins and vitamin K antagonists. However, the lack of an accurate laboratory assessment, as well as the lack of a factor xaban (Xa) inhibitor reversal agent, remains a major problem associated with these anticoagulants. LMWHs represent anticoagulant agents with noteworthy efficacy and safety, and they have been explored to improve their outcomes with various nanocarriers through several administration routes. The main problems related to LMWHs have been surmounted, and improved efficiency may be achieved through the use of DDSs.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 the 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

Drug Delivery Systems on Leprosy Therapy: Moving Towards Eradication?

Leprosy disease remains an important public health issue as it is still endemic in several countries. Mycobacterium leprae, the causative agent of leprosy, presents tropism for cells of the reticuloendothelial and peripheral nervous system. Current multidrug therapy consists of clofazimine, dapsone and rifampicin. Despite significant improvements in leprosy treatment, in most programs, successful completion of the therapy is still sub-optimal. Drug resistance has emerged in some countries. This review discusses the status of leprosy disease worldwide, providing information regarding infectious agents, clinical manifestations, diagnosis, actual treatment and future perspectives and strategies on targets for an efficient targeted delivery therapy

Supplementary material from Overcoming clofazimine intrinsic toxicity: statistical modelling and characterization of solid lipid nanoparticles

The aim of this work was to develop solid lipid nanoparticles (SLNs) loaded with clofazimine (CLZ) (SLNs-CLZ) to overcome its intrinsic toxicity and low water solubility, for oral drug delivery. A Box–Behnken design was constructed to unravel the relations between the independent variables in the selected responses. The optimized SLNs-CLZ exhibited the following properties: particle size <i>ca</i> 230 nm, zeta potential of −34.28 mV, association efficiency of 72% and drug loading of 2.4%, which are suitable for oral delivery. Further characterization included Fourier transformed infrared spectroscopy that confirmed the presence of the drug and the absence of chemical interactions. By differential scanning calorimetry was verified the amorphous state of CLZ. The storage stability studies ensured the stability of the systems over a period of 12 weeks at 4°C. <i>In vitro</i> cytotoxicity studies evidenced no effect of both drug-loaded and unloaded SLNs on MKN-28 gastric cells and on intestinal cells, namely Caco-2 and HT29-MTX cells up to 25 µg ml⁻¹ in CLZ. Free CLZ solutions exhibited IC₅₀ values of 16 and 20 µg ml⁻¹ for Caco-2 and HT29-MTX cells, respectively. It can be concluded that the optimized system, designed considering important variables for the formulation of poorly soluble drugs, represents a promising platform for oral CLZ delivery

Microwave-initiated rapid synthesis of phthalated cashew gum for drug delivery systems

Chemical modification of polysaccharides is an important approach for their transformation into customized matrices that suit different applications. Microwave irradiation (MW) has been used to catalyze chemical reactions. This study developed a method of MW-initiated synthesis for the production of phthalated cashew gum (Phat-CG). The structural characteristics and physicochemical properties of the modified biopolymers were investigated by FTIR, GPC, H NMR, relaxometry, elemental analysis, thermal analysis, XRD, degree of substitution, and solubility. Phat-CG was used as a matrix for drug delivery systems using benznidazole (BNZ) as a model drug. BNZ is used in the pharmacotherapy of Chagas disease. The nanoparticles were characterized by size, PDI, zeta potential, AFM, and in vitro release. The nanoparticles had a size of 288.8 nm, PDI of 0.27, and zeta potential of –31.8 mV. The results showed that Phat-CG has interesting and promising properties as a new alternative for improving the treatment of Chagas disease