Recent strategies for the development of oral medicines for the treatment of visceral leishmaniasis.

Considered prevalent in many countries on five continents, especially in low-income regions, leishmaniasis is a neglected tropical disease classified by World Health Organization as one of the diseases for which the development of new treatments is a priority. It is an infectious disease caused by protozoa of the genus Leishmania, whose species may cause different clinical manifestations, such as cutaneous and visceral leishmaniasis (VL). Treatment is exclusively by drug therapy, as it has not been possible to develop vaccines yet. Currently available drugs are not fully effective in all cases; they have parenteral administration and exhibit a number of serious and very common adverse effects. The only oral drug available is expensive and it is not available in many endemic countries. Injectable administration is the main problem of treatments, since it requires patients to go to health centers, hospitalization and professional administration, which are conditions that are not adapted to the reality of the poverty conditions of patients with the disease. In this context, the development of an oral medicine has become a focus as it may solve many of these issues. Based on this scenario, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs directed to the treatment of human VL.

Herbal Technological Prospects of Morus nigra L.: A Systematic Patent Analysis Review.

BACKGROUND: Morus nigra L. is a plant with significant potential for drug development due to the presence of numerous bioactive compounds in its various parts. OBJECTIVES: This article aims to compile the technological perspectives of Morus nigra L. towards drug development and therapeutic indications based on registered patents in databases. METHODS: The study analyzed patents published within the last five years, focusing on products derived from different parts of the Morus nigra L. plant. Patent databases such as the European Patent Office (EPO), the United States Patent and Trademark Office (USPTO), the World Intellectual Property Organization (WIPO), and the National Institute of Industrial Property Databases (INPI) were examined. RESULTS: A total of 45 patents were categorized by country of origin, type of applicant, extraction method, and therapeutic indications. China had the highest number of patent filings (43.48%), and private companies were the primary technology patent holders (38.64%). Noteworthy extraction methods included ultrasound-assisted extraction, decoction, infusion, and maceration. The most utilized plant parts were leaves (44.44%), followed by fruits (35.56%), root bark (15.56%), and stems (4.44%). The main therapeutic indications identified were the treatment of hyperglycemia and dyslipidemia (43.33%), along with digestive problems, cosmetics, nutrition, and cleaning applications. CONCLUSION: The study of patents covers discoveries and advancements often absent in scientific articles, making a review focused on this advanced information crucial for expanding existing scientific knowledge. Even if some therapies have been explored previously, patents can reveal innovative approaches and fresh perspectives that contribute to sustained scientific progress.

Cutaneous leishmaniasis: new oral therapeutic approaches under development.

The World Health Organization (WHO) classifies leishmaniasis as a disease for which the development of new treatments is a priority. Available drugs are not fully effective in all cases; they have parenteral administration and exhibit serious and common adverse effects. The only oral drug available (miltefosine) has shown resistance, is expensive, and is not available in many endemic countries. Thus, the development of an oral medicine may solve many of these issues. Based on that, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs for the treatment of cutaneous leishmaniasis. A literature search for keywords "leishmania and oral" was performed in PubMed and ScienceDirect, considering articles published in the last 5 years. The articles were selected based on the objective of the review. The main problem in the current treatment of leishmaniasis is the administration of injectables, since it requires patients to travel to health centers, hospitalization, and professional administration, conditions that are not adapted to the socioeconomic reality of patients. Therefore, many research studies have evaluated oral alternatives for the treatment of cutaneous leishmaniasis. The main tested approaches were obtaining new molecules, repositioning drugs, and new formulations of old drugs. The prospects are encouraging but still require more in vivo bioavailability and clinical trials.

A Systematic Review of Functionalized Polymeric Nanoparticles to Improve Intestinal Permeability of Drugs and Biological Products.

BACKGROUND: The oral route is the most frequently used and the most convenient route of drug administration since it has several advantages, such as ease of use, patient compliance, and better costeffectiveness. However, physicochemical and biopharmaceutical limitations of various active pharmaceutical ingredients (API) hinder suitability for this route, including degradation in the gastrointestinal tract, low intestinal permeability, and low bioavailability. To overcome these problems, while maintaining therapeutic efficacy, polymeric nanoparticles have attracted considerable attention for their ability to increase drug solubility, promote the controlled release, and improve stability. In addition, the functionalization of nanocarriers can increase uptake and accumulation at the target site of action, and intestinal absorption, making it possible to obtain more viable, safe and efficient treatments for oral administration. OBJECTIVE: This systematic review aimed to seek recent advances in the literature on the use of polymeric nanoparticles functionalization to increase intestinal permeability of APIs that are intended for oral administration. METHODS: Two bibliographic databases were consulted (PubMed and ScienceDirect). The selected publications and the writing of this systematic review were based on the guidelines mentioned in the PRISMA statement. RESULTS: Out of a total of 3036 studies, 22 studies were included in this article based on our eligibility criteria. The results were consistent for the application of nanoparticle functionalization to increase intestinal permeability. CONCLUSION: The functionalized polymeric nanoparticles can be considered as carrier systems that improve the intestinal permeability and bioavailability of APIs, with the potential to result, in the future, in the development of oral medicines.

Non-fermented Dairy Desserts with Potentially Probiotic Autochthonous Lactobacilli and Products from Peel of Jabuticaba (Myrciaria cauliflora).

The influence of two autochthonous lactobacilli strains with probiotic potential (Lactobacillus mucosae CNPC007 and Lactobacillus plantarum CNPC020) in comparison to a commercially available probiotic strain (Lactobacillus rhamnosus LR32) in non-fermented dairy desserts added with ingredients (syrup and hydroethanolic extract) derived from jabuticaba (Myrciaria cauliflora) peels was investigated. L. mucosae showed the best survivability and stability of the studied lactobacilli after processing and during storage, respectively, and also remarkably influenced the texture and sensory features of desserts in comparison to the other strains; L. plantarum achieved viability comparable with the commercial probiotic, above 6 log cfu/g up to the 21st day of the products refrigerated storage. The hydroethanolic extract and syrup from the jabuticaba peel contributed to the phenolic content of the dairy desserts (around 30 mg GAE/100 g) that showed to be able to scavenge DPPH radicals (around 300 g dessert/g DPPH). The different lactobacilli strains did not significantly influence the antioxidant capacity parameters of the desserts (p > 0.05), although the desserts' color was not stable during storage and tended to reduce the acceptability scores of the three trials. Non-fermented dairy desserts with jabuticaba peel ingredients showed to be good sources of phenolic compounds with an antioxidant capacity, offering suitable conditions for the viability maintenance of the autochthonous lactobacilli cultures.

Layered Double Hydroxides as Promising Excipients for Drug Delivery Purposes.

Layered Double Hydroxides (LDH) have received great attention in the development of drug carrier systems. LDHs have become intelligent excipients of high technological potential for the pharmaceutical industry due to their ability to intercalate biomaterials in the interlayer region, adsorb substances on its vast surface area, have flexible structure, swelling properties, high chemical and thermal stability, modulate drug release, have high biocompatibility and be easily synthesized. This article, using typical examples, mainly addresses the systems formed between LDHs and antimicrobial, antineoplastic and anti-inflammatory agents, which constitute the main pharmacological classes of wide interest due to the problems encountered with low solubility, control in administration, stability in body fluids and toxicity, among others. Additionally, the article also reports on the recent development of ternary or quaternary (multicomponent systems) compounds based on LDH, bringing the advantages of targeted therapy, improving the aqueous stability of nanohybrids and the performance of these inorganic carriers.

Lipid Nanoparticles as a Skin Wound Healing Drug Delivery System: Discoveries and Advances.

Chronic wounds are a remarkable cause of morbidity, requiring long-time treatments with a significant impact on the quality of life and high costs for public health. Although there are a variety of topical skin preparations commercially available, they have several limitations that frequently impair wound healing, such as drug instability, toxicity, limited time of action and ineffective skin permeation. In recent years, researchers have focused on the development of new effective treatments for wound healing and shown frequent interest in nanometric drug delivery systems to overcome such obstacles. In dermatology, lipid nanoparticles (LNPs) have received great attention from researchers due to their great functionalities, greater adhesion to the skin and film formation, enabling the hydration and maintenance of skin integrity, as well as present a more effective penetration through the skin barrier. This review provides an update on topical formulations based on Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) as wound healing treatments. Both SLNs and NLCs are able to increase solubility and stability of active pharmaceutical ingredients and increase skin penetration compared to the free drugs. Additionally, SLNs and NLCs can increase pharmacological activity, increase the release profile of the drugs, promote synergistic effects and improve the sensory properties of the final formulation. Topical dosage forms containing nanoparticles have been extensively evaluated for wound healing activity, mainly the dressings, films and scaffolds. Therefore, lipid nanoparticles have contributed in improving wound healing therapies when incorporated into other dosage forms with better efficacy and lesser adverse effects than conventional formulations.