Analytical techniques to recognize inclusion complexes formation involving monoterpenes and cyclodextrins: A study case with (-) borneol, a food ingredient.

Monoterpenes are non-polar secondary metabolites widely used by industry due to their excellent therapeutic, food-ingredient and cosmetic properties. However, their low solubility in water limits their use. In this sense, cyclodextrins (CDs) have been widely used to solve these technological challenges. Thus, this study aims to use (-)-borneol as a monoterpene model to prepare inclusion complexes between ß-CD and hydroxypropyl-ß-CD (HP-ß-CD) through different ways and characterize them in order to choose the best inclusion method to improve physicochemical properties of monoterpenes. To achieve this goal, the samples were prepared by physical mixture (PM), paste complex (PA) and freeze-drying complex (FD) and then, extensively characterized by thermal analysis, Fourier-transform infrared spectroscopy, scanning electron microscopy, size particle, X-ray diffraction and nuclear magnetic resonance. The physicochemical results showed that freeze-drying was more effective to form inclusion complexes between (-)-borneol with both CDs. This research highlights the importance of recognizing the best method to prepare inclusion complexes, including food additives as (-)-borneol, to achieve better results in food preparations.

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.

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.

Pharmacokinetics and pharmacodynamics of the injectable formulation of methadone hydrochloride and methadone in lipid nanocarriers administered orally to horses.

We investigated the thermal, electrical and mechanical antinociceptive and physiological effects (heart rate, respiratory rate, arterial blood pressure, head height and abdominal auscultation score), and pharmacokinetics, of 0.5 mg/kg of the injectable formulation (ORAL) or nanoparticulated methadone (NANO) given orally, in six adult mares, using a crossover, blind and prospective design. Repeated-measure models were used to compare parametric data between and within treatments, followed by Tukey's test. Nonparametric data were analysed with Wilcoxon signed-rank, adjusted by Bonferroni tests. Blood samples were also collected up to 6 h after dosing for plasma drug quantification by LC-MS/MS. Methadone pharmacokinetic parameters were determined by noncompartmental and compartmental approaches. There were no differences in pharmacodynamic parameters. No statistical differences were observed in the pharmacokinetic parameters from noncompartmental analysis for both groups, except a significant decrease in peak plasma concentration, increase in apparent volume of distribution per fraction absorbed (Vdss /F) and increased mean residence time (MRT) for NANO. One-compartment open model with first order elimination best described the pharmacokinetic profiles for both groups. Neither ORAL nor NANO administered orally to horses produced antinociception. The nanoencapsulated formulation of methadone given orally to horses did not improve methadone pharmacokinetic parameters or increased systemic body exposure to methadone.

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.

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.

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.

Influence of nanoencapsulation on the sensory properties of cosmetic formulations containing lipoic acid.

Sensory analysis has become a valuable tool in qualifying consumer perception regarding cosmetic products. This study aims to explore the application of discriminative and affective consumers sensory analysis in evaluating the influence of nanoencapsulation on the sensory properties and rheological characteristics of a cosmetic formulation containing lipoic acid. The nanocapsules were prepared by the pre-formed polymer precipitation method. Semisolid formulations were prepared using a silicone emulsion system, and these pseudoplastic fluids were characterized using rheological methods. The panellists (n = 88) analysed the formulations with and without nanoencapsulated lipoic acid as paired comparisons within the discriminative and affective sensory analysis. In these measurements, spreadability, stickiness, oiliness and sulphur odour were evaluated. The panellists had no previous training in conducting these measurements. It was shown that nanotechnology can change some sensory characteristics of the formulations. The spreadability, stickiness and oiliness are the attributes for which the panellists noted differences with statistical significance. The spreadability difference could be due to the results found in the rheological profiles and consistency indexes between formulations. In the discriminative analysis, the panellists could not detect any noticeable differences in the sulphur odour or residual properties between samples, attributes that would influence whether consumers adhered to the selected treatment. Considering affective analysis, the consumers communicated that the formulation containing the nanoencapsulated lipoic acid, which presented less consistency, was preferred based on the reduction in immediate stickiness and residual sulphur odour. The free lipoic acid formulation was preferred in terms of residual oiliness and spreadability.

Levodopa microparticles for pulmonary delivery: photodegradation kinetics and LC stability-indicating method.

Levodopa, (S)-2-amino-3-(3,4-dihydroxyphenyl) propanoic acid, is still considered the gold standard treatment for Parkinson's disease. However, oral levodopa shows poor pharmacokinetics and its efficacy becomes problematic with the progression of the disease. Pulmonary delivery using the association of the polymers: chitosan, hyaluronic acid and HPMC, represents a novel approach to overcome this problem. A stability-indicating liquid chromatography method for the quantitative determination of levodopa microparticles for pulmonary delivery was developed as well as its photodegradation kinetics in solution. The developed and validated method was applied for the analyses of the novel formulation as well as for protocols of stability studies.

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.

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.

Drying polymeric drug-loaded nanocapsules: the wet granulation process as a promising approach.

The industrial development of polymeric nanoparticle suspensions is still limited due to their low physicochemical stability. In this paper, we evaluated the wet granulation process as an alternative method to dry polymeric nanocapsules using dexamethasone as drug model. Nanocapsule suspensions were used as granulating liquid as well as a drug-loaded-nanocarrier in the wet granulation process. Granules were evaluated regarding their drug content, mean particle size, yield, moisture content, flow properties, stability on storage, recovery studies after water redispersion and morphological characteristics (SEM). Granules containing dexamethasone-loaded polymeric nanocapsules presented good drug content (approximately 94%) and were stable for 6 months at room temperature. Morphological analyses showed nanostructures on their surface and the nanoparticles were recovered after redispersing the granules in water. These results suggest that wet granulation can be an interesting alternative to dry drug-loaded nanocapsule suspensions.

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.

Microparticles containing lemongrass volatile oil: preparation, characterization and thermal stability.

Lemongrass volatile oil (LVO) is an important ingredient in cosmetics, presenting antimicrobial properties, in particular antifungal activity, and it is a promising raw material for the development of pharmaceutical products. However, its volatility and susceptibility to degradation are the major drawbacks for the use of Cymbopogon citratus oil in pharmaceutical compounding. Thus, the aim of this work was to develop and to characterize microparticles containing this oil viewing the stabilization of LVO. Two techniques of preparation were evaluated; spray drying and precipitation, and two encapsulation materials, beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) were tested. The microparticles were characterized in terms of content of water, yield, percentage of inclusion, infrared spectroscopy. Morphology was evaluated by scanning electronic microscopy. Studies of stability were also conducted. The content of citral (neral and geranial), major component of the oil, present in microparticles was assayed by a validated HPLC method. The percentage of inclusion of LVO into the microparticles was 56-60% and 26-29% using beta-CD and HP-beta-CD, respectively. The results showed that the use of the beta-CD as encapsulant material was more efficient. Additionally, an increased inclusion of lemongrass oil was observed with the precipitation technique.

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. EXPERIMENTAL APPROACH: The following models of inflammation were employed: carrageenan-induced acute oedema (measured between 30 min and 4 h), sub-chronic oedema induced by complete Freund's adjuvant (CFA) (determined between 2 h and 72 h), and CFA-induced arthritis (oedema measured between 14 and 21 days). KEY RESULTS: IndOH or IndOH-NC produced equal inhibition of carrageenan-elicited oedema. However, IndOH-NC was more effective in both the sub-chronic (33 +/- 4% inhibition) and the arthritis (35 +/- 2% inhibition) model of oedema evoked by CFA, when compared with IndOH (21 +/- 2% and 14 +/- 3% inhibition respectively) (P < 0.01). In the CFA arthritis model, treatment with IndOH-NC markedly inhibited the serum levels of the pro-inflammatory cytokines tumour necrosis factor alpha and IL-6 (by 83 +/- 8% and 84 +/- 11% respectively), while the levels of the anti-inflammatory cytokine IL-10 were significantly increased (196 +/- 55%). The indices of gastrointestinal damage in IndOH-NC-treated animals were significantly less that those after IndOH treatment (58 +/- 16%, 72 +/- 6% and 69 +/- 2%, for duodenum, jejunum and ileum respectively). CONCLUSIONS AND IMPLICATIONS: IndOH-NC produced an increased anti-inflammatory efficacy in long-term models of inflammation, allied to an improved gastrointestinal safety. This formulation might represent a promising alternative for treating chronic inflammatory diseases, with reduced undesirable effects.

Nanoencapsulation as a way to control the release and to increase the photostability of clobetasol propionate: influence of the nanostructured system.

The aim of this study was to prepare and to evaluate the physicochemical and in vitro drug release characteristics of different nanostructured systems containing clobetasol propionate (CP): CP-loaded polymeric nanoparticles (nanocapsules and nanospheres) and CP-loaded nanoemulsion. Physicochemical characteristics of the formulations were monitored up to 9 months after preparation by means of drug content, encapsulation efficiency, mean size, polydispersity index, pH, and zeta potential. In vitro drug release studies were carried out using the dialysis bag method. Photostability of CP-loaded nanoparticles was evaluated by their exposition to UVA radiation. All formulations presented nanometric mean size (140-220 nm), polydispersity index below 0.25, neutral pH values, negative zeta potential and encapsulation efficiency close to 100%. All these parameters, except pH, remained unchangeable up to 9 months of storage at room temperature for CP-loaded nanocapsules. On the other hand, CP-loaded nanospheres and nanoemulsion showed an increase in their mean size, as well as in polydispersity index under storage (after 3 and 6 months, respectively). In vitro drug release studies showed a controlled release of CP from nanoparticles (nanocapsules > nanospheres > nanoemulsion) with a low burst release. Photostability of CP under UVA radiation was improved by its incorporation into nanoparticles (nanocapsules > nanoemulsions > nanospheres).

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.

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.