Efeito promotor de beta-ciclodextrinas modificadas na permeação in vitro do estradiol

Estradiol, o mais importante hormônio feminino, foi complexado com hidroxipropil-beta-ciclodextrina (HP-beta-CD) e metil-beta-ciclodextrina randômica (RM-beta-CD). Após a obtenção dos complexos, os mesmos foram caracterizados por estudos de solubilidade, CDV e RMN-H¹. O efeito das CDs sobre a absorção/retenção do estradiol na pele foi investigado in vitro em células de difusão de Franz. As CDs aumentaram a solubilidade aquosa do estradiol em diferentes proporções. As análises de CVD e RMN-H¹ comprovaram a complexação do estradiol com ambas CDs, sendo que RM-beta-CD apresentou interação mais forte com estradiol do que HP-beta-CD. Mais adiante, a formação de complexos aumentou o fluxo de estradiol através da pele (PEstradiol, the most important hormone in females, was complexed with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and randomly methylated beta-cyclodextrin (RM-b-CD). After obtaining the inclusion complexes, they were characterized by DSC, ¹H-NMR and solubility studies. The enhancing effect of CDs on estradiol skin permeation/retention was investigated in vitro using Franz diffusion cells. Both CDs increased estradiol aqueous solubility, but in different proportions. DSC and NMR-H¹ analyses showed that estradiol was complexed with both CDs and RM-beta-CD has stronger interactions with the hormone than HP-beta-CD. Moreover, complexes formation increased estradiol flux through the skin (

Preliminary biocompatibility investigation of magnetic albumin nanosphere designed as a potential versatile drug delivery system

Background: The magnetic albumin nanosphere (MAN), encapsulating maghemite nanoparticles, was designed as a magnetic drug delivery system (MDDS) able to perform a variety of biomedical applications. It is noteworthy that MAN was efficient in treating Ehrlich’s tumors by the magnetohyperthermia procedure. Methods and materials: In this study, several nanotoxicity tests were systematically carried out in mice from 30 minutes until 30 days after MAN injection to investigate their biocompatibility status. Cytometry analysis, viability tests, micronucleus assay, and histological analysis were performed. Results: Cytometry analysis and viability tests revealed MAN promotes only slight and temporary alterations in the frequency of both leukocyte populations and viable peritoneal cells, respectively. Micronucleus assay showed absolutely no genotoxicity or cytotoxicity effects and histological analysis showed no alterations or even nanoparticle clusters in several investigated organs but, interestingly, revealed the presence of MAN clusters in the central nervous system (CNS). Conclusion: The results showed that MAN has desirable in vivo biocompatibility, presenting potential for use as a MDDS, especially in CNS disease therapy

Ampla caracterização do Glioblastoma e abordagens terapêuticas doi: http://dx.doi.org/10.5892/ruvrv.2012.102.1225

Os gliomas são considerados tumores primários do sistema nervoso central, representando apenas 2% dos casos de câncer e o glioblastoma multiforme (GBM) é a forma mais comum e com pior prognóstico dos tumores da glia do sistema nervoso central. O GBM é caracterizado pela alta taxa proliferativa e migratória juntamente com a ausência de apoptose, o que o torna altamente agressivo. Atualmente o tratamento para o glioblastoma depende da localização, do tipo de célula e do grau de  malignidade da mesma. Entretanto, não existe um tratamento eficiente disponível para o GBM, apesar dos inúmeros avanços nas técnicas de cirurgia, radioterapia e quimioterapia, este tipo de neoplasia, ainda continua sendo, um dos maiores desafios para a oncologia. A Terapia Fotodinâmica (PDT) vem sendo amplamente utilizada nos tratamentos de tumores sólidos e sua ação terapêutica se dá pela absorção de luz por um fármaco fotossensibilizante, o que resulta numa cascata de eventos fotofísicos, fotoquímicos e fotobiológicos, que induzem em última instancia  a apoptose e/ou necrose das células que foram marcadas de forma eficiente pelo  fármaco fotosensibilizante. Dessa forma, este trabalho de revisão bibliográfica aborda as principais características do glioblastoma e as perspectivas de novos tratamentos para este tipo de tumor, os quais utilizam a PDT

Chloroaluminium phthalocyanine polymeric nanoparticles as photosensitisers : photophysical and physicochemical characterisation, release and phototoxicity in vitro.

Nanoparticles of poly(D,L-lactide-co-glycolide), poly(D,L-lactide) and polyethylene glycol-blockpoly (D,L-lactide) were developed to encapsulate chloroaluminium phthalocyanine (AlClPc), a new hydrophobic photosensitiser used in photodynamic therapy (PDT). The mean nanoparticle size varied from 115 to 274 nm, and the encapsulation efficiency ranged from 57% to 96% due to drug precipitation induced by different types of polymer. All nanoparticle formulations presented negative zeta potential values (–37 mV to –59 mV), explaining their colloidal stability. The characteristic photophysical parameters were analysed: the absorption spectrum profile, fluorescence quantum yield and transient absorbance decay, with similar values for free and nanoparticles of AlClPc. The time-resolved spectroscopy measurements for AlClPc triplet excited state lifetimes indicate that encapsulation in nanocapsules increases triplet lifetime, which is advantageous for PDT efficiency. A sustained release profile over 168 h was obtained using external sink method. An in vitro phototoxic effect higher than 80% was observed in human fibroblasts at low laser light doses (3 J/cm2) with 10 lM of AlClPc. The AlClPc loaded within polymeric nanocapsules presented suitable physical stability, improved photophysical properties, sustained released profile and suitable activity in vitro to be considered a promising formulation for PDT

Chitosan nanoparticles loaded with epigallocatechin-3-gallate: synthesis, characterisation, and effects against <i>Streptococcus mutans</i> biofilm

This study evaluated the effects of chitosan nanoparticles loaded with epigallocatechin-3-gallate (EGCG) against Streptococcus mutans biofilm. EGCG-loaded chitosan (Nchi + EGCG) nanoparticles and Chitosan (Nchi) nanoparticles were prepared by ion gelation process and characterised regarding particle size, polydispersion index, zeta potential, and accelerated stability. S mutans biofilms were treated twice daily with NaCl 0.9% (negative control), Nchi, Nchi + EGCG, and chlorhexidine (CHX) 0.12% (positive control). After 67 h, the biofilms were evaluated for acidogenesis, bacterial viability and dry weight. Biofilm morphology and structure were analysed by scanning electron microscopy. The nanoformulations presented medium to short-term stability, size of 500 nm, and polydispersion index around 0.400. Treatments affected cell morphology and biofilm structure. However, no effects on microbial viability, biofilm dry weight, and acidogenesis were observed. Thus, the nanoformulations disassembled the biofilm matrix without affecting microbial viability, which makes them promising candidates for the development of dental caries preventive and therapeutic agents.</p

Antimicrobial photodynamic therapy against pathogenic bacterial suspensions and biofilms using chloro-aluminum phthalocyanine encapsulated in nanoemulsions

Antimicrobial photodynamic therapy represents an alternative method of killing resistant pathogens. Efforts have been made to develop delivery systems for hydrophobic drugs to improve the photokilling. This study evaluated the photodynamic effect of chloro-aluminum phthalocyanine (ClAlPc) encapsulated in nanoemulsions (NE) on methicillin-susceptible and methicillin-resistant Staphylococcus aureus suspensions and biofilms. Suspensions and biofilms were treated with different delivery systems containing ClAlPc. After the pre-incubation period, the drug was washed-out and irradiation was performed with LED source (660 ± 3 nm). Negative control samples were not exposed to ClAlPc or light. For the suspensions, colonies were counted (colony-forming units per milliliter (CFU/mL)). The metabolic activity of S. aureus suspensions and biofilms were evaluated by the XTT assay. The efficiency was dependent on the delivery system, superficial load and light dose. Cationic NE-ClAlPc and free-ClAlPc caused photokilling of the both strains of S. aureus. For biofilms, cationic NE-ClAlPc reduced cell metabolism by 80 and 73 % of susceptible and resistant strains, respectively. Although anionic NE-ClAlPc caused a significant CFU/ml reduction for MSSA and MRSA, it was not capable of reducing MRSA biofilm metabolism. This therapy may represent an alternative treatment for eradicating resistant strains.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP