How Sorbitan Monostearate Can Increase Drug-Loading Capacity of Lipid-Core Polymeric Nanocapsules.

Lipid-core polymeric nanocapsules are innovative devices that present distinguished characteristics due to the presence of sorbitan monostearate into the oily-core. This component acted as low-molecular-mass organic gelator for the oil (medium chain triglycerides). The organogel-structured core influenced the polymeric wall characteristics disfavoring the formation of more stable polymer crystallites. This probably occurred due to interpenetration of these pseudo-phases. Sorbitan monostearate dispersed in the oily-core was also able to interact by non-covalent bonding with the drugs increasing the drug loading capacity more than 40 times compared to conventional nanocapsules. We demonstrated that the drug-models quercetin and quercetin pentaacetate stabilized the organogel network probably due to interactions of the drug molecules with the sorbitan monostearate headgroups by hydrogen bonding.

Sustained antioxidant activity of quercetin-loaded lipid-core nanocapsules.

Lipid-core nanocapsules (LNC) are vesicular nanocarriers prepared by solvent displacement. LNC have been previously prepared using medium-chain triglyceride and sorbitan monostearate as liquid and solid lipophilic components dispersed in the core, surrounded by poly(epsilon-caprolactone) (PCL). Our objective was to investigate the antioxidant activity of LNC containing quercetin (QUE), a radical scavenger, prepared with octyl methoxycinnamate and sorbitan monostearate as lipophilic core components and PCL as the polymer wall. We selected Saccharomyces cerevisae cells as the proposed biological model. QUE-LNC presented z-average diameter of 212 nm, pH of 5.51 and zeta potential of -11 mV. Multiple light scattering analysis (TurbiscanLab) showed a photon path length of 172 microm. Furthermore, a validated turbidimetric study determined that the density of particles in suspension was 1.66 x 10(13). DSC analysis showed that the melting temperature of PCL shifted to lower values when in contact with octyl methoxycinnamate indicating a molecular interaction. After 1 h (7 h), the QUE-LNC formulation and QUE solution incubated with H2O2 showed cell survival of 84.4% (87.7%) and 65.6% (7.3%), respectively. After 35 h of incubation, cell survival was 31.7% and 0.9%, respectively. The QUE-LNC showed sustained antioxidant activity and potential as a nanostructured material to formulate final products.

Simultaneous control of capsaicinoids release from polymeric nanocapsules.

The nanoencapsulation of capsaicinoids (capsaicin and dihydrocapsaicin) was proposed in this work as a strategy to control their release due to the reservoir characteristics of the nanocapsules. This reservoir property could prolong the topical analgesic effect and reduce the burning sensation and skin irritation caused by the capsaicinoids. The nanocapsules were physicochemically characterized and presented z-average diameter of 153 +/- 7 (PDI < 0.2) and zeta potential of +9.62 +/- 1.48 mV. The pH of the aqueous nanoparticle suspension was 5.72 +/- 0.10, which is suitable for cutaneous application. The total capsaicinoids content was 0.5 mg mL(-1) (64% of capsaicin and 33% of dihydrocapsaicin) and their encapsulation efficiencies were close to 100%. The formulation was stable over 90 days. The in vitro release profiles demonstrated that the release of capsaicin and dihydrocapsaicin was prolonged by means of nanoencapsulation. Moreover, comparing the half-life values, it was observed that the polymeric wall significantly affected the release rates for both capsaicinoids. According to Fick's first law, capsaicin presented higher flux (5.6 +/- 0.1 (x10(-4)) mg cm(-2) h(-1)) than that of dihydrocapsaicin (2.1 +/- 0.2 (x 10(-4)) mg cm(-2) h(-1)), which was probably related to its higher gradient concentration. Drug diffusion and polymer relaxation were responsible for the capsaicinoids release from the nanocapsules, which fitted the monoexponential mathematical model. This innovative formulation was designed considering its potential action of prolonging the analgesic effect of the capsaicionoids on the skin.

Size-control of poly(epsilon-caprolactone) nanospheres by the interface effect of ethanol on the primary emulsion droplets.

We hypothesized that the control of the poly(epsilon-caprolactone) (PCL) nanosphere sizes could be achieved by controlling the size of the primary emulsion droplets considering a combined effect of the ethanol volume fraction in the organic phase and the stirring rate of the primary emulsion. In this way, we prepared poly(epsilon-caprolactone) (PCL) nanospheres in order to evaluate the effect of those variables on the hydrodynamic diameters of the nanoparticles by a 32 factorial design. The size distribution curves considering intensity, volume and number of particles showed monomodal distributions for all formulations. The nanoparticle diameters (z-average) decreased from 423 to 249 nm with the increase in both the ethanol volume fraction from 0.0 to 0.4 and the stirring rate from 9500 to 17500 rpm. The polydispersity indexes ranged from 0.076 to 0.176. A statistical model based on the regression coefficients calculated by the factorial design analysis was proposed in order to predict the nanoparticle diameters. Using the predictive model, the results showed high similarity between the experimental and the predicted nanosphere diameters, validating the model for loaded PCL nanospheres. The backscattering profiles of the primary emulsions prepared using different proportions of ethyl acetate and ethanol showed a reduction in the size of the droplets from 1.659 microm to 0.706 microm with the increase in the ethanol volume fraction and the stirring rate. Ethanol decreased the restoring stress of the droplets as a consequence of the reduction in the interface tension. The decrease in the nanoparticle mean size was a consequence of the droplet size reduction in the primary emulsion.

Rate-modulating PHBHV/PCL microparticles containing weak acid model drugs.

In this work, we aimed to evaluate the influence of the proportions of poly(epsilon-caprolactone) (PCL) in the poly(hydroxybutyrate-co-hydroxyvalerate) (PHBHV) blended microparticles on the drug release profiles of drug models and to determine the drug release mechanism. Diclofenac and indomethacin used as drug models showed encapsulation efficiencies close to 85%. The average diameters (122-273microm) and the specific surface areas (26-120m(2)g(-1)) of the microparticles were dependent on the PCL concentration in the blends. Differential scanning calorimetry (DSC) analyses showed that the microparticle preparation process influenced the thermal behavior of PHBHV, as well as the glass transition temperature of PHBHV increased with the presence of indomethacin. The release profiles, described by a biexponential equation, showed sustained phase half-lives varying from 131 to 912min (diclofenac) and from 502 to 6300min (indomethacin) depending on the decrease of the PCL concentration. The product between the diffusion coefficient and the drug solubility in the matrix (DC(s,m)), which was proportional to the PCL concentration, was calculated by fitting the release data to the Baker-Lonsdale equation. The mechanism of release was mainly controlled by the drug diffusion and the drug release profiles were controlled by varying the PCL concentration systematically in the blended PHBHV/PCL microparticles.

Semisolid formulation containing a nanoencapsulated sunscreen: effectiveness, in vitro photostability and immune response.

The objective of this work was to verify if hydrophilic gels containing benzophenone-3 loaded nanocapsules (HG-NCBZ3) could improve the sunscreen in vitro effectiveness against UVA radiation and its photostability compared to a conventional hydrogel containing the free sunscreen (HG-BZ3). In parallel, the immune response of the nanostructured system was evaluated by mouse ear swelling test and the local lymph node assay. The nanocapsules were prepared by interfacial deposition of poly(epsilon-caprolactone) and characterized in terms of particle size, polydispersity index, zeta potential, drug content and encapsulation efficiency. HG-NCBZ3 UV scans showed higher absorption intensity values than HG-NCplacebo, prepared using unloaded nanocapsules. Films of the gels were irradiated with UVA light and the BZ3 recovery was evaluated by HPLC. BZ3 recovery decreased from 100% to 29% for HG-BZ3 and to 56% for HG-NCBZ3 after 13 h. After wavelength scans within 13 h, the relative areas under the curves (AUC) decreased from 1.00 to 0.62 for HG-BZ3 and remained constant for HG-NCBZ3. Sensitization assay showed that stimulation indexes lower than 3 for all the hydrogel samples. Formulations did not induce increases higher than 10% in ear swelling, indicating that the hydrogels did not cause cutaneous sensitization in mice. The nanoencapsulation improved both the photostability and the effectiveness of BZ3 compared to the non-encapsulated sunscreen and the topical application of free and nanoencapsulated BZ3 did not produce significant allergy response in mice.

Sustained release from lipid-core nanocapsules by varying the core viscosity and the particle surface area.

Based on the structure of polymeric nanocapsules containing a lipid-dispersed core composed of caprylic/capric trygliceride (CCT) and sorbitan monostearate (SM), we hypothesized that varying the core component concentrations the drug release kinetic could be modulated. Our objective was also to determine the parameters which were responsible for controlling the drug release kinetics. The nanocapsules were prepared by interfacial deposition of poly(epsilon-caprolactone). Interfacial hydrolysis of indomethacin ester (IndOEt) was used to simulate a sink condition of release. Mathematical modeling showed that the IndOEt half-lives increased (198 to 378 and 263 to 508 min) with the increase in the core lipid concentrations, and that the release mechanism was the anomalous transport. By increasing the SM concentration, the diameters were constant (around 250 nm) and the surface areas increased (from 1.06 x 10(4) to 1.51 x 10(4) cm2 x ml(-1)), while by increasing the CCT concentration, the diameters increased (215 to 391 nm) and the surface areas reduced (1.46 x 10(4) to 1.06 x 10(4) cm2 x ml(-1)). The presence of SM increased the viscosity of CCT and the IndOEt apparent permeability decreased from 4.26 x 10(-7) to 2.54 x 10(-7) cm x s(-1), while for CCT series, the apparent permeability was constant around 3.0 x 10(-7) cm x s(-1). A mathematical correlation was established and the IndOEt apparent permeability can be estimated by the SM concentration. In conclusion, varying the CCT and SM concentrations the IndOEt release was controlled by the nanocapsule surface area and by the viscosity of the core, respectively.