IgG functionalized polymeric nanoparticles for oral insulin administration.

The oral route is the best way to administer a drug; however, fitting peptide drugs in this route is a major challenge. In insulin cases, less than 0.5% of the administered dose achieves systemic circulation. Oral delivery by nanoparticles can increase insulin permeability across the intestinal epithelium while maintaining its structure and activity until release in the gut. This system can be improved to increase permeability across intestinal cells through active delivery. This study aimed to improve a nanoparticle formulation by promoting functionalization of its surface with immunoglobulin G to increase its absorption by intestinal epithelium. The characterization of formulations showed an adequate size and a good entrapment efficiency. Functionalized nanoparticles led to a desirable increase in insulin release time. Differential scanning calorimetry, infrared spectroscopy and paper chromatography proved the interactions of nanoparticle components. With immunoglobulin G, the nanoparticle size was slightly increased, which did not show aggregate formation. The developed functionalized nanoparticle formulation proved to be adequate to carry insulin and potentially increase its internalization by epithelial gut cells, being a promising alternative to the existing formulations for orally administered low-absorption peptides.

Sublingual tablets containing spray-dried carvedilol-loaded nanocapsules: development of an innovative nanomedicine.

The aim of this study was to propose the use of spray-dried mucoadhesive carvedilol-loaded nanocapsules in the formulation of sublingual tablets. There is no previous report describing the preparation of tablets containing spray-dried nanocapsules or tablets containing nanocapsules, neither prepared by direct compression nor for sublingual administration. Tablets of 6 mm of diameter and 2.7 ± 0.2 mm of height were obtained with a mean weight of 44 ± 4 mg, carvedilol content of 0.164 ± 0.017 mg, and a disintegration time less than 25 min. They were produced using a force of 4.7 ± 1.6 kgf. The release profile of carvedilol from the tablets was evaluated using the dialysis bag method. In parallel, the release of nanocapsules from the tablet structure into the release medium was evaluated using dynamic light scattering. Nanocapsules that were released from the tablets into the release medium exhibited similar particle size distributions after recovery as in their original liquid suspension, without losing their original ability to control drug release. Therefore, sublingual tablets may be produced from spray-dried drug-loaded nanocapsules using a direct compression technique, providing a useful pharmaceutical approach for drugs that undergo first pass metabolism, such as carvedilol.

New pectin-based hydrogel containing imiquimod-loaded polymeric nanocapsules for melanoma treatment.

We developed a pectin-based hydrogel containing nanocapsules as a new strategy for melanoma treatment. Our first objective was to evaluate the nanoencapsulation effect of imiquimod on melanoma. Imiquimod-loaded polymeric nanocapsules (NCimiq) showed significant time-dependent decrease in cell viability after treatment at 3 µmol L-1 (79% viable cells in 24 h and 55% in 72 h), which was not observed in cells treated with the solution of the drug (IMIQ) (99% viable cells in 24 h and 91% in 72 h). The second objective was to develop the hydrogel containing the drug-loaded nanocapsules (PEC-NCimiq). In vitro release study showed that 63% of imiquimod was released from the pectin-based hydrogel containing the drug (PEC-imiq) after 2 h, while 60% of the drug was released from PEC-NCimiq after 8 h. In the permeation study, 2.5 µg of imiquimod permeated the skin within 8 h after the initial contact of PEC-NCimiq, whereas only 2.1 µg of drug permeated after 12 h of contact when PEC-imiq was assayed. Pectin-based hydrogels enabled the drug penetration in all skin layers, especially the dermis (PEC-NCimiq = 6.8 µg and PEC-imiq = 4.3 µg). In the adhesion study, PEC-NCimiq showed the highest adhesiveness (42% removed from the skin) in comparison to PEC-imiq (71% removed from the skin). In conclusion, the nanoencapsulation provided a higher cytotoxic effect of imiquimod in SK-MEL-28, and the incorporation of the drug-loaded nanocapsules in pectin-based hydrogel showed higher adhesiveness and deeper penetration of the drug into the skin. Graphical abstract.

Anti-HPV Nanoemulsified-Imiquimod: A New and Potent Formulation to Treat Cervical Cancer.

Cervical cancer is associated with the human papilloma virus (HPV) and nowadays is the fourth most frequent cancer among women. One of the treatments for this disease is based on the application of imiquimod. In this study, we postulated that the use of imiquimod in nanoemulsion results in a better antitumoral effect than the drug administered in its nonencapsulated form for the treatment of cervical cancer. Permeability studies using vaginal mucosa, as membrane, and in vitro studies involving cervical cancer cells (viability, clonogenic assay, and cell death analysis) were performed. We showed that low amount of encapsulated imiquimod permeated the vaginal mucosa. However, a higher percentage of cells died after the treatment with low amount (3.0 µmol L-1) of the formulation compared to the free drug. In addition, the innovative formulation presented a combinatory mechanism of cell death involving autophagy and apoptosis. Our results demonstrate that the imiquimod-loaded nanoemulsioncan be an alternative product for the treatment of cervical cancer validating the hypothesis.

Imiquimod-loaded nanocapsules improve cytotoxicity in cervical cancer cell line.

This paper proposes the development of imiquimod-loaded polymeric nanocapsules formulation for the treatment of cervical cancer. The mechanism of death involved in the reduction of the cell viability as well as the production of an inflammation marker (IL-6) after the treatment in cell line SiHa have been evaluated. The formulation has significantly decreased the viability of the cells in a time-dependent manner, after 24, 48 and 72 h. Additionally, results showed a cellular decrease of almost 80% of the cells after 72 h of treatment. The formulation induced death by apoptosis, necrosis, autophagy, and increased the percentage of SubG1subpopulation of SiHa cells after 72 h. After the same time-interval, the formulation significantly prevented the appearance of colonies, showing effectiveness against SiHa. Finally, the formulation stimulated SiHa cells to release IL-6. These findings open new possibilities for the development of aqueous nanosuspension containing imiquimod as a novel strategy for the treatment of cervical cancer.

Doxazosin nanoencapsulation improves its in vitro antiproliferative and anticlonogenic effects on breast cancer cells.

Doxazosin has been evaluated for the treatment of several types of cancer. Here, the antitumor effect of the nanoencapsulated form of doxazosin was evaluated in an in vitro model of breast cancer (MCF7 cell line). Doxazosin-loaded polymeric nanocapsules (DXZ-NC) were produced by interfacial deposition of preformed polymer with homogeneous aspect, spherical shape, mean diameter of about 130nm, positive zeta potential (+5mV), and encapsulation efficiency close to 35%. The Alamar Blue® assay and cell counting were carried out to assess cell viability and cell number, respectively. Mechanism of death was evaluated by Annexin/Propidium Iodide staining, while the long-term response was assessed using the clonogenic assay. Nuclear morphometric analysis was investigated using the NMA technique. A significant decrease in cell viability and clonogenicity was observed after the treatment with DXZ-NC when compared to the non-encapsulated drug. All treatments induced apoptosis as the main mechanism of toxicity. In conclusion, the nanoencapsulation of doxazosin improved its in vitro effects in MCF7 cells, without changing the mechanism of cell death underlying its toxicity. This approach was fundamental to reduce the long-term in vitro ability of the remaining tumor cells to form new colonies after the treatment, potentially reducing the risk of tumor recurrence.

Lipid-core nanocapsules increase the oral efficacy of quercetin in cutaneous leishmaniasis.

New oral treatments are needed for all forms of leishmaniasis. Here, the improved oral efficacy of quercetin (Qc) and its penta-acetylated derivative (PQc) was evaluated in cutaneous leishmaniasis after encapsulation in lipid-core nanocapsules (LNCs) of poly(ε-caprolactone). Leishmania amazonensis-infected BALB/c mice were given 51 daily oral doses of free drugs (16 mg kg-1) or LNC-loaded drugs (0·4 mg kg-1). While treatment with free Qc reduced the lesion sizes and parasite loads by 38 and 71%, respectively, LNC-Qc produced 64 and 91% reduction, respectively. The antileishmanial efficacy of PQc was similar but not as potently improved by encapsulation as Qc. None of the treatments increased aspartate aminotransferase, alanine aminotransferase or creatinine serum levels. These findings indicate that when encapsulated in LNC, Qc and, to a lesser extent, PQc can safely produce an enhanced antileishmanial effect even at a 40-fold lower dose, with implications for the development of a new oral drug for cutaneous leishmaniasis.

Vegetable Oil-Loaded Nanocapsules: Innovative Alternative for Incorporating Drugs for Parenteral Administration.

An innovative nanocapsule formulation for parenteral administration using selected vegetable oils (mango, jojoba, pequi, oat, annatto, calendula, and chamomile) was developed that has the potential to encapsulate various drugs. The vegetable oil-loaded nanocapsules were prepared by interfacial deposition and compared with capric/caprylic triglyceride-loaded lipid core nanocapsules. The major objective was to investigate the effect of vegetable oils on particle size distribution and physical stability and to determine the hemolytic potential of the nanocapsules, considering their applicability for intravenous administration. Taking into account the importance of accurately determining particle size for the selected route of administration, different size characterization techniques were employed, such as Laser Diffraction, Dynamic Light Scattering, Multiple Light Scattering, Nanoparticle Tracking Analysis, and Transmission Electronic Microscopy. Laser diffraction studies indicated that the mean particle size of all nanocapsules was below 300 nm. For smaller particles, the laser diffraction and multiple light scattering data were in agreement (D[3,2]-130 nm). Dynamic light scattering and nanoparticle tracking analysis, two powerful techniques that complement each other, exhibited size values between 180 and 259 nm for all nanoparticles. Stability studies demonstrated a tendency of particle creaming for jojoba-nanocapsules and sedimentation for the other nanoparticles; however, no size variation occurred over 30 days. The hemolysis test proved the hemocompatibility of all nanosystems, irrespective of the type of oil. Although all developed nanocapsules presented the potential for parenteral administration, jojoba oil-loaded nanocapsules were selected as the most promising nanoformulation due to their low average size and high particle size homogeneity.

Skin penetration and dermal tolerability of acrylic nanocapsules: Influence of the surface charge and a chitosan gel used as vehicle.

For an improved understanding of the relevant particle features for cutaneous use, we studied the effect of the surface charge of acrylic nanocapsules (around 150nm) and the effect of a chitosan gel vehicle on the particle penetration into normal and stripped human skin ex vivo as well as local tolerability (cytotoxicity and irritancy). Rhodamin-tagged nanocapsules penetrated and remained in the stratum corneum. Penetration of cationic nanocapsules exceeded the penetration of anionic nanocapsules. When applied on stripped skin, however, the fluorescence was also recorded in the viable epidermis and dermis. Cationic surface charge and embedding the particles into chitosan gel favored access to deeper skin. Keratinocytes took up the nanocapsules rapidly. Cytotoxicity (viability<80%), following exposure for ≥24h, appears to be due to the surfactant polysorbate 80, used for nanocapsules stabilization. Uptake by fibroblasts was low and no cytotoxicity was observed. No irritant reactions were detected in the HET-CAM test. In conclusion, the surface charge and chitosan vehicle, as well as the skin barrier integrity, influence the skin penetration of acrylic nanocapsules. Particle localization in the intact stratum corneum of normal skin and good tolerability make the nanocapsules candidates for topical use on the skin, provided that the polymer wall allows the release of the active encapsulated substance.

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.

Solid lipid nanoparticles containing copaiba oil and allantoin: development and role of nanoencapsulation on the antifungal activity.

The aim of this work was to develop solid lipid nanoparticles (SLN) containing copaiba oil with and without allantoin (NCOA, NCO, respectively) and to evaluate their antifungal activity. Nanoparticle suspensions were prepared using a high homogenisation technique and characterised by dynamic light scattering, laser diffraction, nanoparticle tracking analysis, multiple light scattering analysis, high-pressure liquid chromatography, pH and rheology. The antifungal activities of the formulations were tested in vitro against the emergent yeasts Candida krusei and Candida parapsilosis, and the fungal pathogens of human skin Trichophyton rubrum and Microsporum canis. The dynamic light scattering analysis showed z-average diameters (intensity) between 118.63 ± 8.89 nm for the nanoparticles with both copaiba oil and allantoin and 126.06 ± 9.84nm for the nanoparticles with just copaiba oil. The D[4,3] determined by laser diffraction showed similar results of 123 ± 1.73 nm for the nanoparticles with copaiba oil and allantoin and 130 ± 3.6 nm for the nanoparticles with copaiba oil alone. Nanoparticle tracking analysis demonstrated that both suspensions had monomodal profiles and consequently, the nanoparticle populations were homogeneous. This analysis also corroborated the results of dynamic light scattering and laser diffraction, exhibiting a smaller mean diameter for the nanoparticles with copaiba oil and allantoin (143 nm) than for the nanoparticles with copaiba oil (204 nm). The physicochemical properties indicated that the dispersions were stable overtime. Rheology evidenced Newtonian behaviour for both suspensions. Antifungal susceptibility showed a MIC90 of 125 µg/mL (nanoparticles with copaiba oil) and 7.8 µg/mL (nanoparticles with copaiba oil and allantoin) against C. parapsilosis. The nanoparticles with copaiba oil and the nanoparticles with copaiba oil and allantoin presented a MIC90 of 500 µg/mL and 250 µg/mL, respectively, against C. krusei. The MIC90 values were 500 µg/mL (nanoparticles with copaiba oil) and 1.95 µg/mL (nanoparticles with copaiba oil and allantoin) against T. rubrum. Against M. canis, the nanoparticles with copaiba oil and allantoin had a MIC9 of 1.95 µg/mL. In conclusion, nanoencapsulation improved the antifungal activity of copaiba oil, which was enhanced by the presence of allantoin. The MICs obtained are comparable to those of commercial products and can represent promising therapeutics for cutaneous infections caused by yeasts and dermatophytes.

Penetration, photo-reactivity and photoprotective properties of nanosized ZnO.

The oxidizing capacity and skin penetration of a commercial nanosized ZnO, Nanosun™ (Micronisers-Australia), were evaluated in vitro using porcine skin. Nanosun™ was initially characterized regarding its photo-reactivity and size distribution. An assay using methylene blue was performed to confirm the Nanosun™ photo-reactivity by exposing the labile molecule to UVA irradiation in the presence and absence of the nanosized ZnO. The nanosized ZnO was photo-reactive, reducing the methylene blue concentration to 7% while its concentration remained constant in the control formulation (without ZnO). The product label states that the average particle size is 30 nm. X-ray diffraction, nitrogen sorption and UV-spectrophotometry confirmed the presence of nanometric particles of approximately 30 nm. On the other hand, laser diffractometry showed micrometric particles in the size distribution profile. These analyses indicated that the nanoparticles are arranged as agglomerates and aggregates of micrometric proportions ranging from 0.6 to 60 µm. The skin lipid peroxidation was determined by the formation of thiobarbituric acid reactive species (TBARS) and quantified by UV-spectrophotometry. When exposed to UVA radiation the nanosized ZnO applied porcine skin showed a lower production of TBARS (7.2 ± 1.5 nmol g(-1)) than the controls, the MCT applied porcine skin (18.4 ± 2.8 nmol g(-1)) and the blank porcine skin (14.0 ± 2.0 nmol g(-1)). The penetration of ZnO nanoparticles was studied by scanning electron microscopy and energy dispersive X-ray spectroscopy. The tested ZnO particles did not penetrate into viable layers of the intact porcine skin. The particles tend to accumulate on the skin folds and in these regions they may penetrate into the horny layer.

Nanoencapsulation of tacrolimus in lipid-core nanocapsules showed similar immunosuppressive activity after oral and intraperitoneal administrations.

Tacrolimus is widely used in the prophylaxis of solid-organ transplant rejection. Several studies have reported that tacrolimus has variable and poor bioavailability after oral administration, apart from adverse effects such as gastrointestinal disorders, hyperglycemia, nephro- and neurotoxicity. The aim of this work was to encapsulate tacrolimus (TAC) in lipid-core nanocapsules (LNC) as an oral strategy to deliver the drug. To validate our hypothesis, the pharmacodynamic effect of TAC-LNC was determined after oral and intraperitoneal (i.p.) administrations to mice. TAC-LNC had z-average diameter of 210 nm (unimodal), and 99.5% of encapsulation efficiency. In vitro sustained release was determined for TAC-LNC fitting an anomalous transport mechanism (n = 0.8). TAC-LNC demonstrated higher immunosuppressive activity after oral and i.p. administrations, when compared to the drug solution. TAC-LNC administered at 6.0 mg kg(-1) day(-1) showed equivalent percent reduction in lymphocyte when both routes of administration were used. After oral administration, drug nanoencapsulation allows reducing the dose by at least 40%. Furthermore, the nanoencapsulation of TAC in lipid-core nanocapsules showed pharmacodynamic effect similar for the oral and the i.p. routes. In conclusion, the lipid-core nanocapsules were able to improve the TAC deliver across the oral absorption barrier.

Innovative approach to produce submicron drug particles by vibrational atomization spray drying: influence of the type of solvent and surfactant.

Spray drying is a technique used to produce solid particles from liquid solutions, emulsions or suspensions. Buchi Labortechnik developed the latest generation of spray dryers, Nano Spray Dryer B-90. This study aims to obtain, directly, submicron drug particles from an organic solution, employing this equipment and using dexamethasone as a model drug. In addition, we evaluated the influence of both the type of solvent and surfactant on the properties of the powders using a 3(2) full factorial analysis. The particles were obtained with high yields (above 60%), low water content (below 2%) and high drug content (above 80%). The surface tension and the viscosity were strongly influenced by the type of solvent. The highest powder yields were obtained for the highest surface tension and the lowest viscosity of the drug solutions. The use of ionic surfactants led to higher process yields. The laser diffraction technique revealed that the particles deagglomerate into small ones with submicrometric size, (around 1 µm) that was also observed by scanning electron microscopy. Interaction between the raw materials in the spray-dried powders was verified by calorimetric analysis. Thus, it was possible to obtain dexamethasone submicrometric particles by vibrational atomization from organic solution.

Characterization of rheology and release profiles of olanzapine-loaded lipid-core nanocapsules in thermosensitive hydrogel.

In this study we developed a new drug delivery system for olanzanpine comprised of drug-loaded lipid-core nanocapsules incorporated in a thermosensitive hydrogel, intended to sustain the drug release. Firstly, olanzapine, a hydrophobic drug, was loaded in poly(epsilon-caprolactone) lipid core nanocapsules prepared by interfacial deposition of preformed polymer. The effects of the presence of ethanol and the amounts of sorbitan monostearate and medium-chain triglycerides on the particle size, zeta potential, polydispersity index, presence of microparticles and encapsulation efficiency were investigated using a 2(3) factorial design. The optimized nanocapsules were incorporated into a hydrophilic polymer (Poloxamer 407) dispersion in order to obtain a thermosensitive gel. The formulation containing 0.077 g of sorbitan monostearate, 0.22 ml of medium-chain triglycerides, 3 ml of ethanol and 18% of the thermosensitive polymer was selected according to the physicochemical properties. The rheology and release profiles of the mixed hydrophobic and hydrophilic delivery system were successfully characterized and revealed its great potential for the administration of hydrophobic drugs such as olanzapine with sustained in situ drug release.

Spray-dried powders containing tretinoin-loaded engineered lipid-core nanocapsules: development and photostability study.

The influence of the spray-drying process on the ability of engineered lipid-core nanocapsules to protect tretinoin against UV degradation was evaluated. This approach represents a technological alternative to improve the microbiological stability, storage and transport properties of such formulations. Tretinoin-loaded lipid-core nanocapsules or tretinoin-loaded nanoemulsion were dispersed in lactose (10% w/v) and fed in the spray-drier to obtain a solid product (spray-dried powder containing tretinoin-loaded nanocapsules or nanoemulsion--SD-TTN-NCL or SD-TTN-NE, respectively). SD-TTN-NE showed a lower (p < or = 0.05) percentage of encapsulation (89 +/- 1%) compared to SD-TTN-NCL (94 +/- 2%). Redispersed SD-TTN-NCL and SD-TTN-NE showed z-average sizes of 204 +/- 2 nm and 251 +/- 9 nm, which were close to those of the original suspensions (220 +/- 3 nm and 239 +/- 14 nm, respectively). Similar percentage of photodegradation were determined for tretinoin loaded in nanocapsules (26.15 +/- 4.34%) or in the respective redispersed spray-dried powder (28.73 +/- 6.19 min) after 60 min of UVA radiation exposure (p > 0.05). Our experimental design showed for the first time that spray-dried lipid-core nanocapsules are able to protect tretinoin against UVA radiation, suggesting that the drying process did not alter the supramolecular structure of the lipid-core nanocapsules. Such powders are potential intermediate products for the development of nanomedicines containing tretinoin.

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.

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.

Lipid-core nanocapsules as a nanomedicine for parenteral administration of tretinoin: development and in vitro antitumor activity on human myeloid leukaemia cells.

Tretinoin-loaded conventional nanocapsules have showed a significant protection of this drug against UVC radiation. However, this formulation presents a limited stability on storage. We hypothesized that the association of tretinoin to lipid-core nanocapsules could increase the physicochemical stability of such formulations, focusing on the development of a reliable nanomedicine for parenteral administration. However, this advantage should still be accompanied by the known photoprotective effect of conventional polymeric nanocapsules against the exposure of tretinoin to UV radiation. Results showed that tretinoin-loaded lipid-core nanocapsules improved the physicochemical stability of formulations under storage, without changing their ability to protect tretinoin either against UVA or UVC radiation. In addition, the effect of nanoencapsulation on the antiproliferative and differentiation properties of tretinoin was studied on human myeloid leukemia cells (HL60 cells) showing that tretinoin-loaded lipid-core nanocapsules presents a longer antitumor efficiency compared to the free tretinoin. These results allow us to propose the current formulation (tretinoin-loaded lipid-core nanocapsules) as a promising parenteral nanomedicine for the treatment of acute promyelocytic leukaemia.

Nanocapsules prepared from amorphous polyesters: effect on the physicochemical characteristics, drug release, and photostability.

The influence of the polymeric amorphous materials on the physicochemical and drug release properties of drug-loaded nanocapsules as well as their role on the protection of the entrapped drug against the degradation induced by UV radiation was evaluated. Nanocapsules were prepared by interfacial deposition of preformed polymer (PLA, PLGA 50:50, and PLGA 85:15) using clobetasol propionate as the drug model. In vitro drug release was evaluated by the dialysis bag method. Photochemical stability was studied under UVA radiation. After preparation, all formulations presented nanometric mean size (180-200 nm), polydispersity index below 0.20, acid pH, negative zeta potential, and encapsulation efficiency close to 100%. Clobetasol propionate-loaded PLGA nanocapsules presented a lower physicochemical stability, showing a high drug leakage during 3 months of storage. In vitro studies showed biphasic drug release from all nanocapsules (according to an anomalous transport) and no influence of the hydrophilic characteristics of the amorphous polymeric material on the release rate. The photostability of clobetasol propionate under UVA radiation was improved by its incorporation into PLA and PLGA nanocapsules showing that besides semicrystalline polymers, amorphous polymers could also efficiently protect nanoencapsulated drugs against UV radiation.