Exploring metalloproteins found in the secretion of venomous species: Biological role and therapeutical applications.

Several species during evolution suffered random mutations in response to various environmental factors, which resulted in the formation of venom in phylogenetically distant species. The composition of the venom of most species is poorly known. Snake venom is well characterized while most species have poorly known composition. In contrast, snake venoms are well characterized which proteins and peptides are the main active and most abundant constituents. 42 protein families have been identified, including metalloproteins known as metalloproteinases. These macromolecules are enzymes with zinc in their active site derived from the disintegrin A and metalloproteinase (ADAM) cellular family and are categorized into three classes (PI, PII and PIII) according to their domain organization. The snake venom metalloproteinases (SVMP) are cytotoxic, neurotoxic, myotoxic and/or hematotoxic with a crucial role in the defense and restraint of prey. In this scenario envenoming represents a danger to human health and has been considered a neglected disease worldwide, particularly in tropical and subtropical countries. Nevertheless, recently advances in "omics" technologies have demonstrated interesting biological activities of SVMPs such as antimicrobial, anticancer, against cardiovascular diseases and nervous system disorders. Metalloproteins have the therapeutic potential to be converted into drugs as other components of the venom have undergone this process (e.g., captopril, tirefiban and eptifibatide). So, this chapter is focused on the metalloproteins found in the secretions of venomous species, highlight some aspects such as structure, biological activity, pharmacological therapeutic potential and on.

A Patent Review on the Use of Cyclodextrin Inclusion Complexes to Enhance Physicochemical and Pharmacological Properties in Antidepressant Drugs.

Major depressive disorder is considered one of the most common and prevalent diseases worldwide, affecting children, adults, and the elderly. Currently, several antidepressant drugs are available on the market, but the low adherence of patients due to the slow therapeutic response is a problem to be solved. In this way, cyclodextrins become an alternative to circumvent the limitations and improve the physicochemical and pharmacological properties of this class of drugs. Thus, the objective of this work is to carry out a current review of patents associating antidepressant drugs and cyclodextrins. The patent search was performed in two patent databases, the World Intellectual Property Organization and the European Patent Office using terms in the title and abstract fields and the international patent classification code for antidepressant drugs. In the end, 27 patent documents were selected and divided into three classifications, physical-chemical characterization study, pre-clinical in vivo trials, and clinical trials. The scientific evidence found in the patents considers the use of cyclodextrins as an important alternative to improve the therapeutic and physicochemical properties of antidepressant drugs, among the main improved properties are, solubility, stability, masking taste and odor, bioavailability.

The management of osteoarthritis symptomatology through nanotechnology: a patent review.

Osteoarthritis is considered a degenerative joint disease that is characterised by inflammation, chronic pain, and functional limitation. The increasing development of nanotechnology in drug delivery systems has provided new ideas and methods for osteoarthritis therapy. This review aimed to evaluate patents that have developed innovations, therapeutic strategies, and alternatives using nanotechnology in osteoarthritis treatment. The results show patents deposited from 2015 to November 2021 in the online databases European Patent Office and World Intellectual Property Organisation. A total of 651 patents were identified for preliminary assessment and 16 were selected for full reading and discussion. The evaluated patents are focused on the intraarticular route, oral route, and topical route for osteoarthritis treatment. The intraarticular route presented a higher patent number, followed by the oral and topical routes, respectively. The development of new technologies allows us to envision a promising and positive future in osteoarthritis treatment.

Antibacterial drugs and cyclodextrin inclusion complexes: a patent review.

INTRODUCTION: Bacterial antibiotic resistance occurs when bacteria mutate and escape the effect of antibiotics, which makes the antibiotics no longer effective in treating infections. New solutions for bacterial infections are a persistent need including the identification of drugs with better pharmacological profiles, more potent, and safer. Cyclodextrins inclusion complexes have been able to improve the physicochemical and pharmacological properties of the formulation molecules, resulting in new alternatives with better efficacy. AREAS COVERED: The patents analyzed in the review used treatments based on antibiotics already on the market, natural products, and synthesized molecules composed of the formulation with cyclodextrins. The combination between cyclodextrin and nanostructures also were presented in the patents review process. Moreover, inclusion complexes have been an alternative in developing treatment mainly in China by the pharmaceutical industries in several countries such as Germany, Hungary, the United States of America, Japan and China. EXPERT OPINION: This review is broad and complete since it considers the first patent involving cyclodextrins and antibacterial drugs. Therefore, the various inclusion complexes and antibacterial drugs alternatives presented in this review offer therapeutic options to fight bacterial infections. If shown to be effective, these drugs may be extremely important in the current clinical practice.

Advances of nanosystems containing cyclodextrins and their applications in pharmaceuticals.

For many years, researchers have worked with supramolecular structures involving inclusion complexes with cyclodextrins. These studies have resulted in new commercially available drugs which have been of great benefit. More recently, studies using nanoparticles, including nanosystems containing cyclodextrins, have become a focus of academic research due to the versatility of the systems and their remarkable therapeutic potential. This review focuses on studies published between 2002 and 2018 involving nanosystems containing cyclodextrins. We consider the type of nanosystems, their importance in a health context, the physicochemical techniques used to show the quality of these systems and their potential for the development of novel pharmaceutical formulations. These have been developed in recent studies which have mainly been focusing on basic science with no clinical trials as yet being performed. This is important to note because it means that the studies do not include any toxicity tests. Despite this limitation, the characterization assays performed suggest that these new formulations may have therapeutic potential. However, more research is required to assess the efficacy and safety of these nanosystems.

Evaluation of the antibacterial and modulatory potential of α-bisabolol, ß-cyclodextrin and α-bisabolol/ß-cyclodextrin complex.

The present study aimed to evaluate the antibacterial and modulatory potential of α-bisabolol, ß-cyclodextrin and α-bisabolol/ß-cyclodextrin complex. The minimum inhibitory concentration was determined through the broth microdilution technique using the bacterial strains: Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. The drugs norfloxacin, imipenem and gentamicin were used in the tests, and the compounds α-bisabolol and ß-cyclodextrin; all the compounds were diluted in DMSO. To obtain the minimum inhibitory concentration (MIC) a serial microdilution of the substances in volumes corresponding to the sub-inhibitory concentration (MIC/8), and microdilution with the antibiotic until the penultimate well were performed. The results showed that ß-cyclodextrin did not present synergistic effects when combined with the antibiotics. It was found that α-bisabolol presented a synergistic effect against S. aureus, when combined with the antibiotic norfloxacin. Moreover, α-bisabolol presented synergism against E. coli when combined with gentamicin. The results of this study show that α-bisabolol presents a modulatory synergistic effect for some antibiotics, as gentamicin, and this is an interesting result against multidrug resistant bacteria (MDR). By other side, the complexation of α-bisabolol with ß-cyclodextrin apparently reduces the modulatory effect, maybe due the polarity enhancement of the polarity of α-bisabolol, affecting the interaction of this compound with the cell membrane bilayer. However, more studies are necessary to demonstrate or not these interactions.