RESUMO
The encapsulation of lipophilic drugs in polymeric nanoparticles can form simultaneously both polymeric nanoparticles and drug nanocrystals. The objective was to detect the presence of nanocrystals in the nanoparticle suspensions using a simple methodology, and to determine if the nanocrystals are formed during preparation or by drug leakage from the particles during storage. Indomethacin was chosen as drug model. Unloaded and drug-loaded (1mg/mL) nanocapsules showed diameters close to 280nm and polydispersity lower than 0.20, remaining constant after 120 days. Comparing indomethacin loaded (3mg/mL) and unloaded formulations, variations in the scattered light depolarization degree indicated the simultaneous presence of nanocrystals and nanocapsules in the suspensions. A relation between the scattered light intensities and the drug precipitation was established. As a function of time, when the decrease in the Rayleigh ratios occurred, the drug contents decreased due to precipitation. On the other hand, when the Rayleigh ratios slightly increase, the drug contents are constant. The nanocrystals formed in the oversaturated formulations, agglomerate and precipitate during storage. When the drug is adsorbed on the nanocapsules, but the system is not oversaturated, no nanocrystal was formed and the formulation is physico-chemically stable at least for 150 days of storage.
Assuntos
Indometacina/química , Nanocápsulas , Polímeros/química , Adsorção , Precipitação Química , Cristalização , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Luz , Tamanho da Partícula , Espalhamento de Radiação , Fatores de TempoRESUMO
Nanocapsules are vesicular drug carriers constituted of an oil core, a polymeric wall, and surfactants. A general understanding about the influence of the polymeric wall of nanocapsules on the release profiles of drugs is not known. So, this work was devoted to characterize formulations prepared without polymer or containing it at different concentrations. The indomethacin ethyl ester was used as model and the strategy was based on its interfacial alkaline hydrolysis simulating a sink condition for the release. The antiedematogenic activity in rats for ester-loaded-nanocarriers was also evaluated. The nanocapsules (NC) and nanoemulsion (NE) presented particle sizes below 300 nm, polydispersity lower than 1.2 and pH around 5. SAXS analyses showed that the sorbitan monostearate is dissolved in the oil and the polymer presents regions of crystallinity independently on the PCL concentration. TEM analyses showed droplets (NE) and spherical particles (NC). The time for the total disappearance of the ester varied from 12 h to 24 h depending on the polymer concentration. The biexponential model showed that the indomethacin ester was essentially entrapped within the nanocarriers in an extension of 85 to 95%. The half-lives varied from 147 to 289 min for the sustained phases and from 3 to 6 min for the burst phases. The ester-loaded-NC showed significant antiedematogenic activity, while the ester-loaded-NE did not inhibit the carrageenin-induced paw edema. The nanocapsules promoted the absorption of the indomethacin ethyl ester and the presence of the polymer is important to achieve the pharmacological effect.
Assuntos
Cápsulas/química , Edema/tratamento farmacológico , Indometacina/análogos & derivados , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Álcalis/química , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Edema/patologia , Hidrólise , Indometacina/administração & dosagem , Indometacina/química , Masculino , Microscopia Eletrônica de Transmissão , Conformação Molecular , Tamanho da Partícula , Ratos , Ratos Wistar , Resultado do Tratamento , Difração de Raios XRESUMO
The aim of this work was to establish models and to differentiate the kinetic release behavior of drug models from nanocapsules, nanoemulsion and nanospheres by physico-chemical characterization and release experiments. SAXS analysis showed that the polymer is organized in the nanocapsules, while in the nanospheres the sorbitan monostearate is organized and acts as an impurity of the poly(epsilon-caprolactone) suggesting that constituents in these nanocarriers are differently organized. Formulations presented particle sizes ranging from 178 to 297 nm, probe content from 0.981 to 0.997 mg/mL, pH values from 4.90 to 5.10 and zeta potential from -37.9 to -51.9 mV. The kinetic experiments showed that the nanostructures present similar behaviors when the probe is adsorbed on the nanocarriers (indomethacin-loaded formulations). However, when the probe is entrapped within the nanocarriers (indomethacin ethyl ester-loaded formulations), nanocapsules, nanospheres and nanoemulsion presented different kinetic behaviors. Mathematical modeling of the release profiles was conducted, showing that the presence of the polymer increases the half-lives of the burst phases (5.9, 4.4 and 2.7 min) while the presence of the oil increases the half-lives of the sustained phases (288.8, 87.7 and 147.5 min) for nanocapsules, nanospheres and nanoemulsion, respectively.