Characterization and basic guidelines for the quality control of chitosan for drug delivery in pharmaceutical applications

Chitosan is increasingly used as an alternative to synthetic polymers due to its water solubility, biodegradability, and biological activity. In this work, chitosan samples from three suppliers were evaluated and characterized by physicochemical methods in an attempt to analyze pharmaceutical applications. The degree of deacetylation (DD) was determined by 1H NMR, IR spectra, potentiometric titration, and UV spectrophotometry. The analysis was supplemented by the techniques of DSC, TG, loss on drying, pH of the suspension, heavy metals, sulphated ash, and triple detector size exclusion chromatography (TriSEC). The use of UV, IR, and 1H NMR techniques to determine the degree of deacetylation, limit testing for heavy metals and sulphated ash to analyze inorganic waste, and TriSEC to analyze molecular weights and molecular distribution are recommended as basic requirements for pharmaceutical applications.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Evaluation of biodegradable implants based on polymer blends: development, characterization and in vitro release studies

Implants prepared with polymer blends [poly (e-caprolactone)-poly(lactide), PCL-PLA] at different rates were developed from microspheres. Approximately 19% of dexamethasone acetate was encapsulated into the microspheres, and it was not dependent on polymer characteristics. DSC studies suggested that there is not any signal of interaction between the polymers and the drug and also no influence of any residual solvent in the microspheres. Infrared analysis indicated the chemical stability of the drug even in the blend matrix. The developed devices present low degradation rate. 34% and 21% of dexamethasone acetate was released from PLA and PCL alone implants at 10 weeks, respectively. Intermediate amounts were released from the devices prepared at different PLA-PCL ratios in such a way that the higher the amount of PCL, the slower was the drug release. This study demonstrates that polymeric drug delivery systems allowed to a prolonged release of dexamethasone acetate in vitro.Colegio de Farmacéuticos de la Provincia de Buenos Aire

An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis

Amphotericin B (AmpB) is active against leishmaniasis, but its use is hampered due to its high toxicity observed in patients. In this study, a nanoparticles-delivery system for AmpB (NQC-AmpB), containing chitosan and chondroitin sulfate molecules, was evaluated in BALB/c mice against Leishmania amazonensis. An in vivo biodistribution study, including biochemical and toxicological evaluations, was performed to evaluate the toxicity of AmpB. Nanoparticles were radiolabeled with technetium-99m and injected in mice. The products presented a similar biodistribution in the liver, spleen, and kidneys of the animals. Free AmpB induced alterations in the body weight of the mice, which, in the biochemical analysis, indicated hepatic and renal injury, as well as morphological damage to the kidneys of the animals. In general, no significant organic alteration was observed in the animals treated with NQC-AmpB. Mice were infected with L. amazonensis and treated with the nanoparticles or free AmpB; then, parasitological and immunological analyses were performed. The NQC-AmpB group, as compared to the control groups, presented significant reductions in the lesion size and in the parasite burden in all evaluated organs. These animals presented significantly higher levels of IFN-γ and IL-12, and low levels of IL-4 and IL-10, when compared to the control groups. The NQC-AmpB system was effective in reducing the infection in the animals, and proved to be effective in diminishing the toxicity evoked by AmpB, which was observed when it was administered alone. In conclusion, NQC-AmpB could be considered a viable possibility for future studies in the treatment of leishmaniasisThis work was supported by grants from Pró-Reitoria de Pesquisa from UFMG (Edital 01/2014), Instituto Nacional de Ciência e Tecnologia em Nano-biofarmacêutica (INCT-Nanobiofar), FAPEMIG (CBB-APQ-00496-11 and CBB-APQ-00819-12), and CNPq (APQ-472090/2011-9 and APQ-482976/2012-8). MACF is a grant recipient of FAPEMIG/CAPES. EAFC, VNC, and AAGF are grant recipients of CNPq. Eduardo AF Coelho and André AG Faraco are co-senior authors of this stud

Antileishmanial activity and mechanism of action from a purified fraction of Zingiber officinalis Roscoe against Leishmania amazonensis

In recent years, considerable attention has been given to identify new antileishmanial products derived from medicinal plants, although, to date, no new effective compound has been recently applied to treat leishmaniasis. In the present study, the antileishmanial activity of a water extract from Zingiber officinalis Roscoe (ginger) was investigated and a purified fraction, named F10, was identified as responsible by this biological activity. The chemical characterization performed for this fraction showed that it is mainly composed by flavonoids and saponins. The water extract and the F10 fraction presented IC50 values of 125.5 and 49.8 μg/mL, respectively. Their selectivity indexes (SI) were calculated and values were seven and 40 times higher, respectively, in relation to the value found for amphotericin B, which was used as a control. Additional studies were performed to evaluate the toxicity of these compounds in human red blood cells, besides of the production of nitrite, as an indicator of nitric oxide (NO), in treated and infected macrophages. The results showed that both F10 fraction and water extract were not toxic to human cells, and they were able to stimulate the nitrite production, with values of 13.6 and 5.4 μM, respectively, suggesting that their biological activity could be due to macrophages activation via NO production. In conclusion, the present study shows that a purified fraction from ginger could be evaluated in future works as a therapeutic alternative, on its own or in association with other drugs, to treat disease caused by L. amazonensis

Relaxation of three solenoidal wells and characterization of extremal three-phase H-measures

We fully characterize quasiconvex hulls for three arbitrary solenoidal ( divergence free) wells in dimension three. With this aim we establish weak lower semicontinuity of certain functionals with integrands restricted to generic two-dimensional planes and convex in ( up to three) rank-2 directions within the planes. Within the framework of the theory of compensated compactness, the latter represents an example when the differential constraints fail the constant rank condition but nevertheless the so-called Lambda-convexity still implies lower semicontinuity and A-quasiconvexity ( which essentially means that rank-2 convexity implies S-quasiconvexity-that is quasiconvexity in the sense of the divergence-free differential constraints-on the planes). The proof employs a version of Muller's estimates of Haar wavelet projections in terms of the Riesz transform. The above semicontinuity result is then applied to the three solenoidal wells problem via analogs of Sverak's "nontrivial" quasiconvex functions and connectedness properties of the rank-2 envelopes. As another application of the semicontinuity result, we obtain a "geometric" result of a more general nature: characterization of certain extremal three-point H-measures for three-phase mixtures ( of three characteristic functions) in dimension three. We also discuss the applicability of the results to problems with other differential constrains, in particular to three linear elastic wells, and further generalizations