Paula dos Santos Chaves

Co-encapsulation of resveratrol and curcumin in lipid-core nanocapsules improves their in vitro antioxidant effects

Resveratrol and curcumin are natural antioxidants found in the human diet that have been used in the prevention and treatment of different diseases associated with oxidative stress. Aiming to improve the antioxidant effects of resveratrol and curcumin, lipid-core nanocapsules containing the combination of both polyphenols were developed. Physicochemical characteristics were evaluated and compared to the formulations containing each polyphenol individually. Co-encapsulation did not influence nanotechnological characteristics, and all formulations presented mean diameter around 200 nm, low polydispersity index, and encapsulation efficiency close to 100%. Nanoencapsulation increases the photostability of resveratrol and curcumin, and co-encapsulation improves resveratrol photostability. The in vitro antioxidant activity of polyphenols against HO radicals was enhanced by nanoencapsulation, and a better effect was observed after their co-nanoencapsulation. Also, nanocapsules exhibited controlled release profile, for both polyphenols. The results showed that the strategy to co-encapsulate resveratrol and curcumin is a promising approach to improve the performance of medicines used to prevent and treat diseases associated with oxidative stress.

3D printed tablets loaded with polymeric nanocapsules: An innovative approach to produce customized drug delivery systems

The generation of multi-functional drug delivery systems, namely solid dosage forms loaded with nano-sized carriers, remains little explored and is still a challenge for formulators. For the first time, the coupling of two important technologies, 3D printing and nanotechnology, to produce innovative solid dosage forms containing drug-loaded nanocapsules was evaluated here. Drug delivery devices were prepared by fused deposition modelling (FDM) from poly(ε-caprolactone) (PCL) and Eudragit® RL100 (ERL) filaments with or without a channelling agent (mannitol). They were soaked in deflazacort-loaded nanocapsules (particle size: 138nm) to produce 3D printed tablets (printlets) loaded with them, as observed by SEM. Drug loading was improved by the presence of the channelling agent and a linear correlation was obtained between the soaking time and the drug loading (r2=0.9739). Moreover, drug release profiles were dependent on the polymeric material of tablets and the presence of the channelling agent. In particular, tablets prepared with a partially hollow core (50% infill) had a higher drug loading (0.27% w/w) and faster drug release rate. This study represents an original approach to convert nanocapsules suspensions into solid dosage forms as well as an efficient 3D printing method to produce novel drug delivery systems, as personalised nanomedicines.

Prednisolone-loaded nanocapsules as ocular drug delivery system: development, in vitro drug release and eye toxicity

Abstract Objective: To develop non-toxic aqueous ocular drug delivery systems containing prednisolone by means of its nanoencapsulation. Materials and methods: Nanocapsules were prepared by interfacial deposition of preformed polymer [poly(ε-caprolactone) or Eudragit® RS100]. Particle size distribution was determined by laser diffractometry, photon correlation spectroscopy and nanoparticle tracking analysis. Ocular irritation and cytotoxicity were evaluated in vitro on the chorioallantoic membrane (CAM) and rabbit corneal epithelial cell line, respectively. Results and discussion: Nanocapsules showed mean particle sizes between 100 and 300 nm and prednisolone encapsulation efficiency of around 50%. Controlled release of prednisolone occurred for 5 h for both formulations according to the biexponential model. Both formulations were found to be non-irritant in the CAM test and non-cytotoxic toward rabbit corneal epithelial cells. Conclusions: Encapsulation of prednisolone in nanocapsules was reported for the first time, being suitable for producing eye drops for the treatment of ocular inflammatory and no eye toxicity was indicated.

Redispersible liposomal-N-acetylcysteine powder for pulmonary administration: development, in vitro characterization and antioxidant activity.

Liposomal dry powders of N-acetylcysteine (SD-NAC-Lip) were developed for pulmonary administration. Liposomes were prepared by reverse phase evaporation and spray dried using lactose (10%, w/w) as drying adjuvant. The powders were characterized according to process yield, drug content, residual water content, particle size distribution, morphology and redispersion behavior. In vitro aerosol performance was evaluated using an eight-stage Andersen Cascade Impactor. Moreover, in vitro antioxidant activity was determined by measuring thiobarbituric acid reactive species (TBARS) present in the lungs of healthy Wistar rats after induction of oxidation by iron/EDTA. The spray-drying process had a high yield (71%±2), drug content (mg/g) according to the expected value, moisture content below 9%, geometric mean diameter under 3μm with span value lower than 1. Spherical particles were observed by scanning electron microscopy. Liposomal dry-powders were able to recover the nanometric size of the original dispersion after their redispersion in aqueous medium, as shown by laser diffraction and transmission electron microscopy. Furthermore, the powders presented aerodynamic diameter of about 7μm and respirable fraction above 30%, indicating suitable properties for pulmonary use. The encapsulation of N-acetylcysteine in liposomes was essential to maintain its in vitro antioxidant activity after the drying process. In addition, the powder containing the encapsulated drug had better in vitro antioxidant activity than the liquid and solid formulations containing the non-encapsulated drug, which makes it a good candidate for the treatment of pulmonary diseases associated with oxidative stress.

The use of chitosan as cationic coating or gel vehicle for polymeric nanocapsules: Increasing penetration and adhesion of imiquimod in vaginal tissue

&NA; The human papillomavirus (HPV) infection, which is strongly related to cervical cancer, can be reduced by the topical application of imiquimod. Some strategies have been used to increase the adhesion and penetration of drugs through the vaginal mucosa. Two of them are the development of mucoadhesive semisolid formulations and the development of polymeric nanocarriers. In this paper, we hypothesize that the combined use of these two strategies results in a better performance of the formulation to retain imiquimod into the vaginal tissue. Aiming this, two different systems are proposed: (a) chitosan‐coated poly(&egr;‐caprolactone)‐nanocapsules incorporated into hydroxyethylcellulose gel (HEC‐NCimiq‐chit), and (b) poly(&egr;‐caprolactone)‐nanocapsules incorporated into chitosan hydrogel (CHIT‐NCimiq). These formulations were submitted to three main tests: mucoadhesivity by interaction, permeation and washability test (or retention test). We developed an integrative index that allows comparing the global performance of the proposed formulations by considering jointly the results of these three tests. Thus, when considered the integrative indexes for the formulations, our results show that CHIT‐NCimiq presents the best performance for the treatment of HPV. Graphical abstract Figure. No caption available.

Ciprofloxacin-loaded lipid-core nanocapsules as mucus penetrating drug delivery system intended for the treatment of bacterial infections in cystic fibrosis

Treatment of bacterial airway infections is essential for cystic fibrosis therapy. However, effectiveness of antibacterial treatment is limited as bacteria inside the mucus are protected from antibiotics and immune response. To overcome this biological barrier, ciprofloxacin was loaded into lipid-core nanocapsules (LNC) for high mucus permeability, sustained release and antibacterial activity. Ciprofloxacin-loaded LNC with a mean size of 180nm showed a by 50% increased drug permeation through mucus. In bacterial growth assays, the drug in the LNC had similar minimum inhibitory concentrations as the free drug in P. aeruginosa and S. aureus. Interestingly, formation of biofilm-like aggregates, which were observed for S. aureus treated with free ciprofloxacin, was avoided by exposure to LNC. With the combined advantages over the non-encapsulated drug, ciprofloxacin-loaded LNC represent a promising drug delivery system with the prospect of an improved antibiotic therapy in cystic fibrosis.

Castor oil and mineral oil nanoemulsion: development and compatibility with a soft contact lens

Abstract Context: The non-invasive ophthalmic therapy has a drawback: low residence time in the eye socket. Nanoparticles and contact lenses have been studied as promising ocular drug delivery systems. Objective: To develop a nanoemulsion and evaluate its compatibility with a soft contact lens as a potential strategy for ocular delivery. Materials and methods: The formulations were developed by spontaneous emulsification and fully characterized. Two drops of nanoemulsion were instilled on the surface of a commercial contact lens and its transparency was measured using a UV-Vis spectrophotometer. Before and after the instillation of the drops, the morphology (scanning electron microscopy – SEM) and ion permeability of the lenses were analyzed. Results: The formulations had a mean particle size of 234 nm, polydispersity below 0.16, zeta potential of −8.56 ± 3.49 mV, slightly acid pH, viscosity ≈1.2 mPa s−1 and spherical-shaped particles. Nanoemulsion was non-irritant (hen’s egg test-chorioallantoic membrane), which was confirmed by the cytotoxicity studies in the SIRC cell cultures. After instillation, SEM analysis showed nanodroplets inside and on the surface of the lenses, although their transparency remained near 100%. No significant differences were found between lens ion permeability coefficients before and after instillation. Conclusions: Formulations presented appropriate physicochemical characteristics and suitability for ocular application. The contact lens remained transparent and ion-permeable after association with the formulation.

Carvedilol-loaded nanocapsules: Mucoadhesive properties and permeability across the sublingual mucosa

&NA; Carvedilol is a drug used to treat heart failure, hypertension, and coronary artery diseases. However, it has low oral bioavailability (25–35%) due to its high first‐pass hepatic metabolism. The objective of this study was to develop carvedilol‐loaded mucoadhesive nanocapsules as delivery systems for the sublingual administration of the drug. Nanocapsules were prepared using poly(&egr;‐caprolactone) (CAR‐LNC) and Eudragit® RS 100 (CAR‐NC) as polymeric wall. In vitro interaction of formulations with mucin was performed to predict their mucoadhesion capacity. The permeability and washability profiles of carvedilol were evaluated using porcine sublingual mucosa. The mean diameter of particles in formulations was in the nanometric range, and particles had low polydispersity and slightly acidic pH. Zeta potential values were positive for CAR‐NC and negative for CAR‐LNC. Encapsulation efficiency was higher than 87% and 99% for CAR‐NC and CAR‐LNC, respectively. Both formulations presented controlled drug release profiles and mucoadhesive properties. Carvedilol was able to permeate through the sublingual mucosa. Nanoencapsulation improved retention time on the mucosa and permeation in presence of simulated salivary flux. This study highlighted the suitability of using CAR‐loaded nanocapsules in the development of innovative sublingual dosage forms. Graphical abstract Figure. No caption available. HighlightsCarvedilol was encapsulated in Eudragit® RS 100 or poly(&egr;)caprolactone nanocapsules.Interaction of nanocapsules with mucin and porcine sublingual mucosa was evidenced.Nanoencapsulated carvedilol was able to cross porcine sublingual mucosa.Nanoencapsulation improved carvedilol permeation in presence of simulated salivary flux.

Redispersible spray-dried nanocapsules for the development of skin delivery systems: proposing a novel blend of drying adjuvants

ABSTRACT This study proposes a novel blend of drying adjuvants (lactose and polyvinylpyrrolidone) as an approach to produce dispersible powders containing nanocapsules for the development of skin delivery systems. Hydrogels were produced with liquid nanocapsules and spray-dried powders. Nanoparticle recovery was obtained after powder aqueous redispersion. No influence of the intermediate product was observed on the hydrogel properties and on the drug release profile. The novel blend of drying adjuvants is a smart approach to obtain dried nanocapsules with excellent aqueous redispersion and to maintain the drug release profile of the original suspension in the design of novel skin delivery systems.

Applications of Polymeric Nanoparticles in Oral Diseases: A Review of Recent Findings

Polymeric nanoparticles are promising drug delivery systems due to their physicochemical properties, which may be explored to improve the treatment and prevention of several diseases, including oral conditions. Moreover, the pharmacological effects of polymers may be improved by nanostructuration. Therefore, this article provides a detailed review of the studies published between 2010 and 2017 covering the use of polymeric nanoparticles in the treatment and/or prevention of oral diseases. A brief description about the dental biofilm and oral diseases is presented in first part of the article. The following section includes an important discussion about the strategies studied to improve the treatment and prevention of these diseases using polymeric nanoparticles: (i) a better drug antibacterial effect, (ii) the release of the drug in a time-controlled way, (iii) the increase of drug uptake by cells, (iv) the cytotoxicity in tumor cells and solubility in water, and (v) mucoadhesive drug delivery systems. Furthermore, the composition and size of the polymeric nanoparticles explored by these strategies were described. Finally, in the last part of this review, the in vitro and in vivo results which demonstrate the effect of these systems in the treatment and/or prevention of the most prevalent oral disorders were highlighted: dental carious lesions, oral cancer, and periodontal and endodontic diseases.