Angiogenesis is a physiological process involving the growth of new blood vessels, which provides oxygen and required nutrients for the development of various pathological conditions. In a tumor microenvironment, this process upregulates the growth and proliferation of tumor cells, thus any stage of angiogenesis can be a potential target for cancer therapies. In the present study, chitosan and his derivatives have been used to design novel polymer-based nanoparticles. The therapeutic potential of these newly designed nanoparticles has been evaluated. The antioxidant and MTT assays were performed to know the antioxidant properties and their biocompatibility. The in vivo antiangiogenic properties of the nanoparticles were evaluated by using a chick Chorioallantoic Membrane (CAM) model. The obtained results demonstrate that chitosan derivatives-based nanostructures strongly enhance the therapeutic effect compared to chitosan alone, which also correlates with antitumor activity, demonstrated by the in vitro MTT assay on human epithelial cervical Hep-2 tumor cells. This study opens up new direction for the use of the chitosan derivatives-based nanoparticles for designing of antiangiogenic nanostructured materials, for future cancer therapy.While stimulation of angiogenesis in cancer leads to metastasis, the anti-angiogenic therapy proved to be an important approach against tumor growth. In this respect, it is a well-known fact that the consumption of antioxidants can be recommended to achieve the inhibition of angiogenesis or reversal of unwanted cell-cell adherence [1]. Several studies have been conducted to investigate the connection between antioxidants and pathological angiogenesis, thus leading to mixed conclusions from studies that have been associated with a lower total cancer incidence with the use of antioxidants [2], to studies that have highlighted the lack of any benefit of using antioxidants on the incidence of cancer [3]. All these results are, for certain ones, closely related with the type of antioxidant included in the study (alpha tocopherol, beta-carotene, ascorbic acid) and the investigated tumor location and not least the investigated pharmaceutical formulation. In this context, the use of antioxidants in the form of nanoparticles could improve the efficiency of this therapy due to specific surface area of nanostructures [4], thereby ensuring better contact with cells that would increase the chances of pathological angiogenesis inhibition. However, to have more success in cancer therapy, more studies should be conducted in this direction.Chitosan is a natural cationic polymer exhibits three chemical reactive sites including a primary amine and two primary or secondary hydroxyl groups for further modification [5][6][7]. Nano/microparticles coated with chitosan, synthesized through different techniques for encapsulation (chemical, physical and mechanical techniques), are in continuous development, aiming at the entrapment of bioactive substances, enzymes, hormones, antimicrobial agents, vitamins, mi...

One of the most common adverse effects, in the case of medicines used voluntarily or not, of over dosage, or even of drugs administered in therapeutic doses, is hepatic injury, which is why, in the pharmaceutical research, the experimental compounds are assessed before and during clinical trials, so that only compounds that prove to be safe for commercial use will be approved. In our case, compounds obtained prior to this study were evaluated from a biological point of view, following in vitro tests, establishing the antimicrobial potential, on bacterial strains and fungal strains. In addition, in vivo tests were performed on mice, for completing the pharmacotoxicological profile: evaluation of the hepatic markers (GPT, GOT, alkaline phosphatase, total serum cholesterol and serum albumin). The results demonstrate that different structural modulations of isoniazid can favourably influence the antimicrobial activity and may lead to an improvement of liver markers, after oral administration. RezumatUnul dintre cele mai frecvente efecte adverse, în cazul medicamentelor utilizate în mod voluntar sau nu, a unei doze excesive, sau chiar a medicamentelor administrate în doze terapeutice, este lezarea hepatică, motiv pentru care, în cercetarea farmaceutică, compușii experimentali sunt evaluați înainte și în timpul studiilor clinice, astfel încât doar cei care se dovedesc a fi siguri pentru utilizare, vor fi aprobați. În cazul nostru, compușii obținuți anterior acestui studiu, au fost evaluați din punct de vedere biologic, prin teste in vitro, stabilind potențialul antimicrobian, pe tulpini bacteriene și tulpini fungice. În plus, testele in vivo efectuate pe șoareci de laborator, au fost realizate pentru completarea profilului farmacotoxicologic: evaluarea markerilor hepatici (TGP, TGO, fosfatază alcalină, colesterol seric total și albumină serică). Rezultatele obținute demonstrează că diferitele modificări structurale ale izoniazidei pot influența în mod favorabil activitatea antimicrobiană ș i pot duce la o îmbunătățire a markerilor hepatici, după administrarea pe cale orală.

Lately, in the world of medicine, the use of polymers for the development of innovative therapies seems to be a major concern among researchers. In our case, as a continuation of the research that has been developed so far regarding obtaining new isoniazid (INH) derivatives for tuberculosis treatment, this work aimed to test the ability of the encapsulation method to reduce the toxicity of the drug, isoniazid and its new derivatives. To achieve this goal, the following methods were applied: a structural confirmation of isoniazid derivatives using LC-HRMS/MS; the obtaining of microparticles based on polymeric support; the determination of their loading and biodegradation capacities; in vitro biocompatibility using MTT cell viability assays; and, last but not least, in vivo toxicological screening for the determination of chronic toxicity in laboratory mice, including the performance of a histopathological study and testing for liver enzymes. The results showed a significant reduction in tissue alterations, the disappearance of cell necrosis and microvesicular steatosis areas and lower values of the liver enzymes TGO, TGP and alkaline phosphatase when using encapsulated forms of drugs. In conclusion, the encapsulation of INH and INH derivatives with chitosan had beneficial effects, suggesting a reduction in hepatotoxicity and, therefore, the achievement of the aim of this paper.

Considering that microbial resistance to antibiotics is becoming an increasingly widespread problem, burn management, which usually includes the use of topical antimicrobial dressings, is still facing difficulties regarding their efficiency to ensure rapid healing. In this context, the main objective of this research is to include new oxytetracycline derivatives in polymeric-film-type dressings for the treatment of wounds caused by experimentally induced burns in rats. The structural and physico-chemical properties of synthesized oxytetracycline derivatives and the corresponding membranes were analyzed by FT-IR and MS spectroscopy, swelling ability and biodegradation capacity. In vitro antimicrobial activity using Gram-positive and Gram-negative bacterial strains and pathogenic yeasts, along with an in vivo study of a burn wound model induced in Wistar rats, was also analyzed. The newly obtained polymeric films, namely chitosan-oxytetracycline derivative membranes, showed good antimicrobial activity noticed in the tested strains, a membrane swelling ratio (MSR) of up to 1578% in acidic conditions and a biodegradation rate of up to 15.7% on day 7 of testing, which are important required characteristics for the tissue regeneration process, after the production of a burn. The in vivo study proved that chitosan-derived oxytetracycline membranes showed also improved healing effects which contributes to supporting the idea of using them for the treatment of wounds caused by burns.

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