Maria Elenir Nobre Pinho Ribeiro

Solubilisation capacity of Brij surfactants

The aim of this study was to investigate the potential of selected Brij non-ionic surfactants for enhancing the solubility of poorly water-soluble drugs. Griseofulvin was selected as a model drug candidate enabling comparisons to be made with the solubilisation capacities of other poly(ethylene oxide)-based copolymers. UV/Vis and (1)H NMR spectroscopies were used to quantify the enhancement of solubility of griseofulvin in 1 wt% aqueous micellar solutions of Brij 78 (C(18)H(37)E(20)), Brij 98 (C(18)H(35)E(20)) and Brij 700 (C(18)H(37)E(100)) (where E represents the OCH(2)CH(2) unit of the poly(ethylene oxide) chain) at 25, 37 and 40 °C. Solubilisation capacities (S(cp) expressed as mg griseofulvin per g Brij) were similar for Brij 78 and 98 (range 6-11 mg g(-1)) but lower for Brij 700 (3-4 mg g(-1)) as would be expected for the surfactant with the higher ethylene oxide content. The drug loading capacity of micelles of Brij 78 was higher than many di- and triblock copolymers with hydrophilic E-blocks specifically designed for enhancement of drug solubility.

Solubilisation of griseofulvin, quercetin and rutin in micellar formulations of triblock copolymers E62P39E62 and E137S18E137.

The solubilisation of two poorly soluble flavonoids, quercetin and rutin, in micellar solutions of mixtures of a block copolymer of ethylene oxide and styrene oxide (E(137)S(18)E(137)) with one of ethylene oxide and propylene oxide (E(62)P(39)E(62)) has been studied at 25 and 37 degrees C. Solubilisation capacities were higher than those for the model poorly water-soluble drug griseofulvin and comparable with published values for the solubilisation of rutin by beta-cyclodextrin.

The effect of polymeric additives on the solubilisation of a poorly-soluble drug in micellar solutions of Pluronic F127.

The solubilisation of griseofulvin in 1wt% aqueous micellar solutions of Pluronic F127 at 37°C has been modified by adding polyethylene glycol PEG 35000 or poly(vinylpyrrolidone) PVP K30. The solubilisation capacity expressed in terms of unit weight of F127 is increased by the addition of 0.5wt% PEG 35000 to a value approaching double that of a 2.5wt% solution of F127 alone, but there is no advantage in adding 0.5wt% PVP K30.

The effect of water-soluble polymers, PEG and PVP, on the solubilisation of griseofulvin in aqueous micellar solutions of Pluronic F127

The purpose of this study was to investigate the possibility of enhancing the solubilisation capacity of micellar solutions of Pluronic F127 for the poorly water-soluble drug griseofulvin by co-formulating with a water-soluble polymer. The effect of the addition of the polyethylene glycols PEG6000 and 35000, and the poly(vinylpyrrolidone)s PVP K30 and K90, on the solubilisation capacity of 1wt% solutions of Pluronic F127 was related to the effect of these additives on particle size as determined by dynamic light scattering measurements. The addition of PEG35000 to 1wt% F127 solutions significantly increased the solubility capacity expressed in terms of unit weight of F127; PVP K90 had a smaller effect but no enhancement was noted following the addition of PEG6000 or PVP K30. Solubilisation enhancement was thought to be a consequence of the association of the polymers with the E-blocks of the micelle corona so providing an expanded region of reduced polarity for drug solubilisation.

Magnetic Nanosystem for Cancer Therapy Using Oncocalyxone A, an Antitomour Secondary Metabolite Isolated from a Brazilian Plant

This paper describes the investigation and development of a novel magnetic drug delivery nanosystem (labeled as MO-20) for cancer therapy. The drug employed was oncocalyxone A (onco A), which was isolated from Auxemma oncocalyx, an endemic Brazilian plant. It has a series of pharmacological properties: antioxidant, cytotoxic, analgesic, anti-inflammatory, antitumor and antiplatelet. Onco A was associated with magnetite nanoparticles in order to obtain magnetic properties. The components of MO-20 were characterized by XRD, FTIR, TGA, TEM and Magnetization curves. The MO-20 presented a size of about 30 nm and globular morphology. In addition, drug releasing experiments were performed, where it was observed the presence of the anomalous transport. The results found in this work showed the potential of onco A for future applications of the MO-20 as a new magnetic drug release nanosystem for cancer treatment.

Solubilisation of griseofulvin in aqueous micellar solutions of diblock copolymers of ethylene oxide and 1,2-butylene oxide with lengthy B-blocks

The influence of hydrophobic-block length on solubilisation capacity was examined for micelles of E(m)B(n) copolymers (E=oxyethylene, B=oxybutylene, subscripts denote number-average block lengths in repeat units) with B-block lengths in the range of 30-76 and with E-blocks of sufficient length to ensure the formation of spherical micelles. Griseofulvin was used as a model poorly-water-soluble drug known to be almost exclusively solubilised in the micellar core. Combination of solubilisation data with those of a previous study has shown that the amount of drug solubilised per gram of hydrophobe is essentially independent of B-block length when this exceeds about 15 B units, suggesting that core size is not a major influence on solubilisation.

Diblock copolymers of ethylene oxide and 1,2-butylene oxide in aqueous solution Formation of unimolecular micelles

The dependence of log(cmc) on hydrophobic block length n was examined for E(m)B(n) copolymers (E=oxyethylene, B=oxybutylene, subscripts denote number-average block lengths in repeat units) with n in the range 30-76. Combination with published data for E(m)B(n) diblock copolymers with shorter E-blocks shows two changes of slope in the log(cmc)-n plot corresponding to the onset of unimolecular micelle formation at n approximately 12 and completion of this process at n approximately 30. The results are discussed with reference to published data for E(m)L(n) and E(m)CL(n) (L from d,L-lactide; CL from epsilon-caprolactone) copolymers, which show similar behaviour.

Binary mixture micellar systems of F127 and P123 for griseofulvin solubilisation

Pluronics® molecules self-assemble in aqueous solution providing a core/shell architecture that improves the solubility of hydrophobic drugs. Binary mixtures of Pluronics® have been studied as drug nanocarriers in order to combine their advantages, like high colloidal stability, small particle size and good solubilisation capacity (Scp). In this work we studied Pluronics® binary mixture, P123 and F127, as nanocarriers of the hydrophobic drug griseofulvin. P123 (E21P67E21) shows a relative good Scp, whereas F127 (E98P67E98) shows a good colloidal stability. According to data, these binary mixtures form stables nano-sized comicelles in aqueous solution. The Scp of the P123/F127 systems at 25 and 37 °C was monitored by UV/Visible spectroscopy, showing good results at both temperatures, as would be expected, since P123/F127 have similar length hydrophobic block. Hydrophobic-dependence and temperature-responsive of the systems were evaluated by CMC, particle size and colloidal stability. Hence, stables P123/F127 comicelles may have potencial as hydrophobic drug delivery.

Novos surfactantes alquil poliglicosídicos à base de amilose extraída da batata inglesa (Solanum tuberosum L.)

Alkyl polyglycosides (APGs) are new biodegradable surfactants, non-toxic, synthesized from abundant renewable sources, potentially more appropriate than anionic surfactants. A range of glycosides denoted APG-Cy was synthesized by the Koenig-Knorr reaction using C10, C16 and C18 alcohols and derived from the degradation of amylose from English potato. The molecular structures of the glycosides were characterized by Nuclear Magnetic Resonance (1H and 13C NMR) together with Infrared Spectroscopy (FTIR) and Gel Permeation Chromatography (GPC). The study by NMR allowed the junctions between hydrophilic head groups and hydrophobic tail-groups to be characterized in detail. Conformation of the glycosidic units is 4C1 type with a b anomeric configuration. The formation of glycosides with five glucose rings linked to the alkyl chain was confirmed by 1H NMR and GPC. Liquid crystals identified by the presence of double melting points were observed by Differential Scanning Calorimetry (DSC) showing thermotropic properties. The surface tension (γ) and critical micelle concentration (cmc) were determined by du Nouy method, noting that increasing the length of alkyl chain led to the expected reduction in the cmc. The energies of adsorption and micellization processes calculated from isotherms γ versus ln c (g.dm-3) indicate cooperativeness of hydrophilic and hydrophobic groups.

Binary Micellar Solutions of Poly(Ethylene Oxide)-Poly(Styrene Oxide) Copolymers with Pluronic® P123: Drug Solubilisation and Cytotoxicity Studies

The non-commercial copolymers E45S8, E45S17 and their mixtures with Pluronic® P123 (E21P67E21) were studied as carriers of the model drug griseofulvin. Critical micelle concentration (cmc) (dye solubilisation method), drug solubilisation capacity (Scp and Sh) determined by ultraviolet-visible (UV-Vis) spectroscopy and 1H nuclear magnetic resonance (1H NMR) and cytotoxicity (LDH activity in human neutrophils) were studied. E45S17 1.0 wt.% dispersions presented colloidal aggregates limiting its Scp in comparison to E45S8, but in 0.1 wt.% solutions this phenomenon seemed to be absent and E45S17 presented a higher Scp. The mixtures that showed the best Scp results contained 50% of P123 and presented low cmc. An evaluation of literature data suggested a minimum Em content of 62% in EmSn copolymers below which the increase of Sn length does not lead to an increase of Sh. The results suggested no toxicity of the copolymers on human neutrophils, supporting the use of P123 and poly(styrene oxide) containing copolymers as drug carriers.