Guterres Ss

Tretinoin-loaded nanocapsules: Preparation, physicochemical characterization, and photostability study.

The aim of this study was to prepare and characterize tretinoin-loaded nanocapsules as well as to evaluate the influence of this nanoencapsulation on tretinoin photostability. Tretinoin-loaded nanocapsules (0.5 mg ml(-1)) were prepared by interfacial deposition of preformed polymer (poly-epsilon-caprolactone) using two different oily phases: capric/caprylic triglycerides and sunflower seed oil. Tretinoin-loaded nanocapsules presented drug content close to the theoretical value, encapsulation efficiencies higher than 99.9%, nanometric mean size with a polydispersity index below 0.25, and pH values between 5.0 and 7.0. Regarding photodegradation studies, tretinoin methanolic solution showed a half-life time around 40 min according to a first order equation, whereas tretinoin nanocapsule suspensions showed a half-life between 85 and 100 min (twofold higher than in methanolic solution) according to a zero order equation. Tretinoin-loaded nanocapsules improved tretinoin photostability, independently on the type of oily phase used in this study, and represent a potential system to be incorporated in topical or systemic dosage forms containing tretinoin.

Effects of indomethacin-loaded nanocapsules in experimental models of inflammation in rats.

Background and purpose:  The effects of systemic treatment with indomethacin‐loaded nanocapsules (IndOH‐NC) were compared with those of free indomethacin (IndOH) in rat models of acute and chronic oedema.

Preparation and characterization of spray-dried polymeric nanocapsules

Recently, much interest has been generated by colloidal drug delivery systems such as nanocapsules because of the possibilities for controlled release, increased drug efficacy, and reduced toxicity after parenteral administration. Nanocapsules of poly-ε-caprolactone and Eudragit S90® were prepared. However, these systems present physicochemical instability. To dry these nanocapsule suspensions with the view of obtaining a solid form, the spray-drying process was used. Spray-dried powders of nanocapsules of poly-ε-caprolactone and Eudragit S90® were prepared by atomization in a Büchi 190 Mini-spray dryer using colloidal silicon dioxide as a technological carrier. The morphological analysis of the surface at the powders showed that nanocapsules remain intact, and no change in particle size was detected after the spray-drying process. These results suggest that this method can be an interesting alternative to dry nanocapsule suspensions.

Lipid-core nanocapsules restrained the indomethacin ethyl ester hydrolysis in the gastrointestinal lumen and wall acting as mucoadhesive reservoirs.

The aim of this work was to investigate if the indomethacin ethyl ester (IndOEt) released from lipid-core nanocapsules (NC) is converted into indomethacin (IndOH) in the intestine lumen, intestine wall or after the particles reach the blood stream. NC-IndOEt had monomodal size distribution (242 nm; PDI 0.2) and zeta potential of -11 mV. The everted rat gut sac model showed IndOEt passage of 0.16 micromol m(-2) through the serosal fluid (30 min). From 15 to 120 min, the IndOEt concentrations in the tissue increased from 6.13 to 27.47 micromol m(-2). No IndOH was formed ex vivo. A fluorescent-NC formulation was used to determine the copolymer bioadhesion (0.012 micromol m(-2)). After NC-IndOEt oral administration to rats, IndOEt and IndOH were detected in the gastrointestinal tract (contents and tissues). In the tissues, the IndOEt concentrations decreased from 459 to 5 microg g(-1) after scrapping, demonstrating the NC mucoadhesion. In plasma (peripheric and portal vein), in spleen and liver, exclusively IndOH was detected. In conclusion, after oral dosing of NC-IndOEt, IndOEt is converted into IndOH in the intestinal lumen and wall before reaching the blood stream. The complexity of a living system was not predicted by the ex vivo gut sac model.

Selective cytotoxicity of indomethacin and indomethacin ethyl ester-loaded nanocapsules against glioma cell lines: an in vitro study.

Gliomas are the most common and devastating tumors of the central nervous system. Several studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) are promising anticancer agents. Biodegradable nanoparticulate systems have received considerable attention as potential drug delivery vehicles. The aim of this study was to evaluate the effects of indomethacin-loaded nanocapsules and indomethacin ethyl ester-loaded nanocapsules on glioma cell lines. In addition, the effect of these formulations on normal neural tissue was also evaluated. In order to investigate this, glioma cell lines (U138-MG and C6) and hippocampal organotypic cultures were used. The main finding of the present study is that indomethacin-loaded nanocapsules formulation was more potent than a solution of indomethacin in decreasing the viability and cell proliferation of glioma lines. Indomethacin and indomethacin ethyl ester associated together in the same nanocapsule formulation caused a synergic effect decreasing glioma cell proliferation. In addition, when the glioma cells were exposed to 25 microM of indomethacin-loaded nanocapsules or indomethacin ethyl ester-loaded nanocapsules, a necrotic cell death was observed. Interestingly, 5 microM of indomethacin-loaded nanocapsules was able to cause an antiproliferative effect without promoting necrosis in glioma cells. Another important finding was that the cytotoxic effect induced by 25 microM or 50 microM of indomethacin-loaded nanocapsules or indomethacin ethyl ester-loaded nanocapsules, in glioma cells was not observed in the organotypic cultures, indicating selective cytotoxicity of those formulations for tumoral cells. Further investigations using in vivo glioma model should be helpful to confirm the distinct effects of indomethacin-loaded nanocapsules and indomethacin ethyl ester-loaded nanocapsules, in normal versus tumoral cells.

Polymeric nanocapsules ultra stable in complex biological media.

Non-specific protein adsorption from complex biological media, especially from blood plasma, is an urgent challenge for the application of nanoparticles as delivery systems, diagnostics, and other biomedical application. Nanocapsules (NC) prepared from FDA-approved degradable poly(ɛ-caprolactone) shell and Mygliol 812(®) oil in the core were coated with mono-methoxy terminated oligo(ethylene glycol) methacrylate (poly(MeOEGMA)) polymer brush layers with a well-controlled thickness at the nanometer scale up to 350 nm using surface initiated atom transfer radical polymerization in water or phosphate buffered saline. Incubation of uncoated NC with human serum albumin solution, fetal bovine serum, or human blood plasma resulted in fast aggregation observed by dynamic light scattering as an increase in diameter of particles present in the solutions. Conversely, these biological fluids affected only marginally the size distribution of the NC coated with a 60 nm thick poly(MeOEGMA) layer. The high suspension stability of the coated NC in complex biological fluids was related to the suppressed deposition of proteins from these fluids observed by surface plasmon resonance (SPR) on analogous poly(MeOEGMA) layer prepared on flat surfaces of SPR chips.

Nanoparticle-coated microparticles: preparation and characterization.

The objective of the present work was to design and prepare new nanoparticle-coated drug-loaded inorganic microparticles by spray-drying using diclofenac as drug model. Previous works presented the process to dry drug-loaded polymeric nanoparticles using silicon dioxide as adjuvant, otherwise in the present proposition the drug is associated with the silicon dioxide and unloaded polymeric nanocapsule or nanosphere suspensions were used as organic coating. Eudragit S100® was chosen because of its gastric resistance. The potential application of polymeric colloidal suspensions as nanocoating for microparticles were evaluated in terms of process yields, encapsulation efficiencies, morphologic analyses and in vitro drug release profiles in buffered media (pH 1.2; 5.0 and 7.4). The results showed the technological feasibility of preparing controlled nanoparticle-coated drug-loaded inorganic microparticles. When the diclofenac was employed as a hydrophilic model, in this salt form, the powders prepared in two steps (core previously prepared) showed an adequate gastroresistance by the use of Eudragit S100®. The use of diclofenac as a hydrophobic model (acid form) conducted to powders presenting good gastroresistance when the nanocapsules and triacetin were employed.

Innovative Sunscreen Formulation Based on Benzophenone-3-Loaded Chitosan-Coated Polymeric Nanocapsules

Aim: To evaluate the effect of cationic coating of polymeric nanocapsules in sunscreen formulations on the in vitro skin penetration of benzophenone-3. Methods: Benzophenone-3-loaded nanocapsules were prepared by the interfacial deposition of poly(Ε-caprolactone) and coated by using a chitosan solution. The nanoparticles were characterized and incorporated in hydrogels. The presence of nanoparticles in hydroxyethyl cellulose gels was observed by transmission electron microscopy and photon correlation spectroscopy. Penetration studies were carried out using Franz cells with porcine skin membranes. Results: Benzophenone-3-loaded chitosan-coated nanocapsules presented a mean size of 202 ± 7 nm and positive zeta potential (+21 ± 1 mV), while these values for the uncoated nanocapsules were 175 ± 1 nm and –8 ± 1 mV. Penetration profiles showed that a higher amount of benzophenone-3 remained at the skin surface and a lower amount was found in the receptor compartment after the application of the formulation containing chitosan-coated nanocapsules compared to a formulation containing its free form. Conclusions: Hydrogel containing benzophenone-3 chitosan-coated nanocapsules represents an innovative formulation to overcome limitations of sunscreen daily use.

Increasing sodium pantoprazole photostability by microencapsulation: effect of the polymer and the preparation technique.

Pantoprazole sodium is a proton pump inhibitor, used in acid-related disorders, like peptic ulcers and gastroesophageal reflux. This drug is unstable in acid solution and in the presence of salts. The aim of this work was to study the photostability under UVC radiation of pantoprazole and to determine its kinetics. A methanol solution and the solid pantoprazole were evaluated by HPLC within 120 min and 10 days, respectively. The work was also dedicated to evaluate and compare the ability of microencapsulation in stabilizing pantoprazole after UVC radiation. Pantoprazole-loaded microparticles prepared by emulsification/solvent evaporation or spray drying were compared. Pantoprazole was encapsulated using Eudragit S100 or its blend with poly(epsilon-caprolactone) or HPMC. In methanol solution, pantoprazole was completely degraded after 120 min and presented zero-order kinetics with t1/2 of 6.48 min. In the solid form, after 10 days, pantoprazole concentration was reduced to 27% following zero-order kinetic. The microparticles prepared only with Eudragit S100 demonstrated an increase of the drug photostability. After 10 days of irradiation, 56 and 44% of the drug was stable when encapsulated by emulsification/solvent evaporation and spray drying, respectively. The use of polymer blends did not improve the pantoprazole photostability.

Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects.

The treatment of various hair disorders has become a central focus of good dermatologic patient care as it affects men and women all over the world. For many inflammatory-based scalp diseases, glucocorticoids are an essential part of treatment, even though they are known to cause systemic as well as local adverse effects when applied topically. Therefore, efficient targeting and avoidance of these side effects are of utmost importance. Optimizing the balance between drug release, interfollicular permeation, and follicular uptake may allow minimizing these adverse events and simultaneously improve drug delivery, given that one succeeds in targeting a sustained release formulation to the hair follicle. To test this hypothesis, three types of polymeric nanocarriers (nanospheres, nanocapsules, lipid-core nanocapsules) for the potent glucocorticoid clobetasol propionate (CP) were prepared. They all exhibited a sustained release of drug, as was desired. The particles were formulated as a dispersion and hydrogel and (partially) labeled with Rhodamin B for quantification purposes. Follicular uptake was investigated using the Differential Stripping method and was found highest for nanocapsules in dispersion after application of massage. Moreover, the active ingredient (CP) as well as the nanocarrier (Rhodamin B labeled polymer) recovered in the hair follicle were measured simultaneously, revealing an equivalent uptake of both. In contrast, only negligible amounts of CP could be detected in the hair follicle when applied as free drug in solution or hydrogel, regardless of any massage. Skin permeation experiments using heat-separated human epidermis mounted in Franz Diffusion cells revealed equivalent reduced transdermal permeability for all nanocarriers in comparison to application of the free drug. Combining these results, nanocapsules formulated as an aqueous dispersion and applied by massage appeare to be a good candidate to maximize follicular targeting and minimize drug penetration into the interfollicular epidermis. We conclude that such nanotechnology-based formulations provide a viable strategy for more efficient drug delivery to the hair follicle. Moreover, they present a way to minimize adverse effects of potent glucocorticoids by releasing the drug in a controlled manner and simultaneously decreasing interfollicular permeation, offering an advantage over conventional formulations for inflammatory-based skin/scalp diseases.