Anti biofilm effect of dihydromyricetin-loaded nanocapsules on urinary catheter infected by Pseudomonas aeruginosa.

Nosocomial infections associated with biofilm formation on urinary catheters are among the leading causes of complications due to biofilm characteristics and high antimicrobial resistance. An interesting alternative are natural products, such as Dihydromyricetin (DMY), a flavonoid which presents several pharmacological properties, including strong antimicrobial activity against various microorganisms. However, DMY, has low aqueous solubility and consequently low bioavailability. Nanoencapsulation can contribute to the improvement of characteristics of some drugs, by increasing the apparent solubility and sustained release has been reported among other advantages. The aim of this study was to evaluate, for the first time, the feasibility of DMY nanoencapsulation, and to look at its influence on nanoencapsulation of DMY as well as verify its influence on antimicrobial and antibiofilm activity on urinary catheters infected by Pseudomonas aeruginosa. The physicochemical characterization showed an average diameter less than 170nm, low polydispersity index, positive zeta potential (between +11 and +14mV), slightly acidic pH. The values of the stability study results showed that the best condition for suspension storage without losing physical and chemical characteristics was under refrigeration (4±2°C). The antibiofilm activity of the formulations resulted in the eradication of biofilms both in free DMY formulations and in nanocapsules of DMY during those periods. However, within 96h the results of the inhibition of biofilm by DMY nanocapsules were more effective compared with free DMY. Thus, the nanocapsule formulation containing DMY can potentially be used as an innovative approach to urinary catheter biofilm treatment or prevention.

Improved tretinoin photostability in a topical nanomedicine replacing original liquid suspension with spray-dried powder with no loss of effectiveness.

OBJECTIVE: The use of spray-dried powders containing tretinoin-loaded nanocapsules instead of the original liquid suspension, aimed at the preparation of dermatological nanomedicines with improved photostability, was investigated. METHODS: Powders were prepared using lactose as a drying adjuvant. Hydrogels were prepared using two approaches: dispersing Carbopol Ultrez 10 in an aqueous redispersion of the powder or incorporating the powder in previously formed hydrogels. RESULTS AND DISCUSSION: The photodegradation of tretinoin in hydrogels prepared with the powders showed similar half-life times (around 19.5 h) compared to preparations with the original liquid nanocapsules (20.7 ± 1.4 h), regardless of the preparation approach. In addition, the topical nanomedicines prepared with the spray-dried powders presented a significant improvement in tretinoin photostability compared to the formulation containing the non-encapsulated drug. CONCLUSION: This study verified that the addition of the spray-dried powders containing tretinoin-loaded lipid-core nanocapsules to hydrogels did not influence the photoprotection of the drug compared with the preparation procedure using the original liquid suspension.

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.

Tablets containing drug-loaded polymeric nanocapsules: an innovative platform.

The aim of the present work was to evaluate the feasibility to convert drug-loaded nanocapsule suspensions in a solid dosage form (tablets). Dexamethasone was used as a model drug due to its low aqueous solubility and fast drug release from conventional tablets. Granules containing dexamethasone-loaded nanocapsules were obtained by a wet granulation process using a dispersion of polyvinylpirrolidone/nanocapsules as a binder system. Granules were compressed in an eccentric compression machine (D-NC-T). A control formulation (tablets without nanocapsules) was also prepared (D-T). Tablets were characterized by means of mean weight, hardness, friability, diameter, thickness, disintegration time, drug content, morphological analysis by scanning electron microscopy (SEM), and in vitro drug release studies. D-NC-T showed adequate physicochemical characteristics according to the pharmacopeial requirements in terms of mean weight, hardness, friability, disintegration time and drug content. Intact nanocapsules in tablets were observed by SEM. In vitro drug release studies showed a slower release of dexamethasone from these tablets (D-NC-T) compared to the control formulation (D-T). Results showed that these tablets represent an interesting platform to the development of oral drug delivery systems containing polymeric nanocapsules.

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.

Hydrogel containing dexamethasone-loaded nanocapsules for cutaneous administration: preparation, characterization, and in vitro drug release study.

CONTEXT: Our group previously reported the development of dexamethasone-loaded polymeric nanocapsules as an alternative for topical dermatological treatments. OBJECTIVE: Our study aimed to prepare and characterize a hydrogel containing this system to improve the effectiveness of the glucocorticoid for cutaneous disorders. METHODS: For the antiproliferative activity assay, a dexamethasone solution and D-NC were tested on Allium cepa root meristem model. D-NC were prepared by the interfacial deposition of preformed polymer. Hydrogels were prepared using Carbopol Ultrez 10 NF, as polymer, and characterized according to the following characteristics: pH, drug content, spreadability, viscosity, and in vitro drug release. RESULTS AND DISCUSSION: Nanocapsules showed mean particle size and zeta potential of 201 +/- 6 and -5.73 +/- 0.42 nm, respectively. They demonstrated a lower mitotic index (4.62%) compared to free dexamethasone (8.60%). Semisolid formulations presented acidic pH values and adequate drug content (between 5.4% and 6.1% and 100% and 105%, respectively). The presence of nanocapsules in hydrogels led to a decrease in their spreadability factor. Intact nanoparticles were demonstrated by TEM as well as by dynamic light scattering (mean particle size < 300 nm). In vitro studies showed a controlled dexamethasone release from hydrogels containing the drug associated to the nanocapsules following the Higuchi's squared root model (k = 20.21 +/- 2.96 mg/cm(2)/h(1/2)) compared to the hydrogels containing the free drug (k = 26.65 +/- 2.09 mg/cm(2)/h(1/2)). CONCLUSION: Taking all these results together, the hydrogel containing D-NC represent a promising approach to treat antiproliferative-related dermatological disorders.

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.