RESUMO
Self-aggregation of Curcumin (Cur) in aqueous biological environment decreases its bioavailability and in vivo therapeutic efficacy, which hampers its clinical use as candidate for reducing risk of neurodegenerative diseases. Here, we focused on the design of new Cur- ß-Cyclodextrin nanoconjugates to improve the solubility and reduce cell toxicity of Cur. In this study, we described the synthesis, structural characterization, photophysical properties and neuron cell toxicity of two new water soluble ß-CD/Cur nanoconjugates as new strategy for reducing risks of neurodegenerative diseases. Cur was coupled to one or two ß-CD molecules via triazole rings using CuAAC click chemistry strategy to yield ß-CD@Cur and (ß-CD)2@Cur nanoconjugates, respectively. The synthesized nanoconjugates were found to be able to self-assemble in aqueous condition and form nano-aggregates of an average diameter size of around 35 and 120 nm for ß-CD@Cur and (ß-CD)2@Cur, respectively. The photophysical properties, water solubility and cell toxicity on rat embryonic cortical neurons of the designed nanoconjugates were investigated and compared to that of Cur alone. The findings revealed that both new nanoconjugates displayed better water solubility and in vitro biocompatibility than Cur alone, thus making it possible to envisage their use as future nano-systems for the prevention or risk reduction of neurodegenerative diseases.
Assuntos
Técnicas de Química Sintética , Curcumina/química , Curcumina/farmacologia , Nanoconjugados/química , beta-Ciclodextrinas/química , Animais , Disponibilidade Biológica , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Curcumina/síntese química , Liberação Controlada de Fármacos , Estrutura Molecular , Nanoconjugados/ultraestrutura , Neurônios/efeitos dos fármacos , Tamanho da Partícula , Ratos , SolubilidadeRESUMO
Photodynamic therapy (PDT) is mainly used to destroy cancerous cells; it combines the action of three components: a photoactivatable molecule or photosensitizer (PS), the light of an appropriate wavelength, and naturally occurring molecular oxygen. After light excitation of the PS, the excited PS then reacts with molecular oxygen to produce reactive oxygen species (ROS), leading to cellular damage. One of the drawbacks of PSs is their lack of solubility in water and body tissue fluids, thereby causing low bioavailability, drug-delivery efficiency, therapeutic efficacy, and ROS production. To improve the water-solubility and/or drug delivery of PSs, using cyclodextrins (CDs) is an interesting strategy. This review describes the in vitro or/and in vivo use of natural and derived CDs to improve antitumoral PDT efficiency in aqueous media. To achieve these goals, three types of binding modes of PSs with CDs are developed: non-covalent CDâ»PS inclusion complexes, covalent CDâ»PS conjugates, and CDâ»PS nanoassemblies. This review is divided into three parts: (1) non-covalent CD-PS inclusion complexes, covalent CDâ»PS conjugates, and CDâ»PS nanoassemblies, (2) incorporating CDâ»PS systems into hybrid nanoparticles (NPs) using up-converting or other types of NPs, and (3) CDs with fullerenes as PSs.
Assuntos
Antineoplásicos/uso terapêutico , Ciclodextrinas/uso terapêutico , Fotoquimioterapia , Antineoplásicos/química , Antineoplásicos/farmacologia , Ciclodextrinas/química , Ciclodextrinas/farmacologia , Fulerenos , Humanos , Luz , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
Curcumin is known for its anti-inflammatory, neuroprotective, and antioxidant properties, but its use in biological applications is hindered by its sensitivity to light, oxygen, and temperature. Furthermore, due to its low water solubility, curcumin has a poor pharmacokinetic profile and bioavailability. In this study, we evaluated the potential application of curcumin as a neuroprotective agent encapsulated in RGD peptide-PEGylated nanoliposomes developed from salmon-derived lecithin. Salmon lecithin, rich in polyunsaturated fatty acids, was used to formulate empty or curcumin-loaded nanoliposomes. Transmission electron microscopy, dynamic light scattering, and nanoparticle tracking analysis characterizations indicated that the marine-derived peptide-PEGylated nanoliposomes were spherical in shape, nanometric in size, and with an overall negative charge. Cytotoxicity tests of curcumin-loaded nanoliposomes revealed an improved tolerance of neurons to curcumin as compared to free curcumin. Wild-type SH-SY5Y were treated for 24 h with curcumin-loaded nanoliposomes, followed by 24 h incubation with conditioned media of SH-SY5Y expressing the Swedish mutation of APP containing a high ratio of Aß40/42 peptides. Our results revealed significantly lower Aß-induced cell toxicity in cells pre-treated with RGD peptide-PEGylated curcumin-loaded nanoliposomes, as compared to controls. Thus, our data highlight the potential use of salmon lecithin-derived RGD peptide PEGylated nanoliposomes for the efficient drug delivery of curcumin as a neuroprotective agent.
RESUMO
Self-aggregation of hydrophobic porphyrin-based photosensitizers (PSs) in aqueous biological environment decreases their bioavailability and in vivo therapeutic efficacy, which hampers their clinical use in photodynamic therapy (PDT). In the current study, we explore three new supramolecular systems based of hydrophobic PSs (i.e. 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP) or 5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin (P1COOH)) non-covalently or covalently attached to ß-CD. The two non-covalent solid inclusion complexes (ß-CD)2/mTHPP and [(ß-CD)/P1COOH]4 are prepared by a new co-precipitation@lyophilization combined method and the covalent conjugate ß-CD-P1 by click chemistry. The binding type effect and effectiveness on the disaggregation in aqueous medium and in vitro PDT efficacy against glioblastoma cancer cells of PSs are investigated for the three ß-CD/PS systems. The findings reveal a remarkable improvement of the disaggregation and in vitro PDT activity of these ß-CD/PS systems compared to the free PSs, except for [(ß-CD)/P1COOH]4 inclusion complex caused by J-type self-aggregation of the inclusion complex in tetrameric form. ß-CD-P1 conjugate shows the higher in vitro PDT efficacy compared to the other ß-CD/PS systems. Overall, the results indicate that the disaggregation in aqueous medium and in vitro PDT activity of hydrophobic PSs can be improved by their binding to ß-CD and the covalent binding is the best approach.
Assuntos
Glioblastoma/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas , beta-Ciclodextrinas , Linhagem Celular Tumoral , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Porfirinas/farmacologia , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacologiaRESUMO
Photodynamic therapy (PDT) has drawn great interest in recent years mainly due to its low side effects and few drug resistances. Nevertheless, one of the issues of PDT is the need for oxygen to induce a photodynamic effect. Tumours often have low oxygen concentrations, related to the abnormal structure of the microvessels leading to an ineffective blood distribution. Moreover, PDT consumes O2. In order to improve the oxygenation of tumour or decrease hypoxia, different strategies are developed and are described in this review: 1) The use of O2 vehicle; 2) the modification of the tumour microenvironment (TME); 3) combining other therapies with PDT; 4) hypoxia-independent PDT; 5) hypoxia-dependent PDT and 6) fractional PDT.