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Transepidermal drug delivery achieves high drug concentrations at the action site and ensures continuous drug delivery and better patient compliance with fewer adverse effects. However, drug delivery through topical application is still limited in terms of drug penetration. Chitosan is a promising enhancer to overcome this constraint, as it can enhance drug diffusion by opening the tight junctions of the stratum corneum. Therefore, here, we developed a novel chitosan nanosponge (CNS) with an optimal ratio and molecular weight of chitosan to improve drug penetration through skin. To prepare the CNS, two types of chitosan (3 and 10 kDa) were each conjugated with poloxamer 407 using para-nitrophenyl chloroformate, and the products were mixed with poloxamer 407 at ratios of 5:5, 8:2, and 10:0. The resulting mixtures were molded to produce flexible soft nanosponges by simple nanoprecipitation. The CNSs were highly stable in biological buffer for four weeks and showed no toxicity in human dermal fibroblasts. The CNSs increased drug permeability through human cadaver skin in a Franz-type diffusion cell, with substantially higher permeability with 3 kDa chitosan at a ratio of 8:2. This suggests the applicability of the novel CNS as a promising carrier for efficient transepidermal drug delivery.

Purpose: The combination of ultrasound and microbubbles can facilitate cellular uptake of (model) drugs via transient permeabilization of the cell membrane. By using fluorescent molecules, this process can be studied conveniently with confocal fluorescence microscopy. This study aimed to investigate the relation between cellular uptake and fluorescence intensity increase of intercalating model drugs.Procedures: SYTOX Green, an intercalating fluorescent dye that displays >500-fold fluorescence enhancement upon binding to nucleic acids, was used as a model drug for ultrasound-induced cellular uptake. SYTOX Green uptake was monitored in high spatiotemporal resolution to qualitatively assess the relation between uptake and fluorescence intensity in individual cells. In addition, the kinetics of fluorescence enhancement were studied as a function of experimental parameters, in particular, laser duty cycle (DC), SYTOX Green concentration and cell line.Results: Ultrasound-induced intracellular SYTOX Green uptake resulted in local fluorescence enhancement, spreading throughout the cell and ultimately accumulating in the nucleus during the 9-min acquisition. The temporal evolution of SYTOX Green fluorescence was substantially influenced by laser duty cycle: continuous laser (100 % DC) induced a 6.4-fold higher photobleaching compared to pulsed laser (3.3 % DC), thus overestimating the fluorescence kinetics. A positive correlation of fluorescence kinetics and SYTOX Green concentration was found, increasing from 0.6 × 10-3 to 2.2 × 10-3 s-1 for 1 and 20 μM, respectively. Finally, C6 cells displayed a 2.4-fold higher fluorescence rate constant than FaDu cells.Conclusions: These data show that the temporal behavior of intracellular SYTOX Green fluorescence enhancement depends substantially on nuclear accumulation and not just on cellular uptake. In addition, it is strongly influenced by the experimental conditions, such as the laser duty cycle, SYTOX Green concentration, and cell line. [ABSTRACT FROM AUTHOR]

Eudragit® RS 30D/silica composite precursor containing either Rhodamine B or sucrose as model drug was dried in a single droplet drying apparatus. Microparticles with distinct core–shell structure were produced by one-step drying for all compositions, while Rhodamine B showed uneven distribution in core and shell regions. At 5% (w/w) loading, it influenced shell formation process by producing dispersible initial shell and altered particle surface morphology into wrinkling appearance, while similar effects were not observed for sucrose. Decreasing the loading to 0.017% reduced the influence. The observations might be attributed to the properties of Rhodamine B, which affect its migration behavior during drying. [ABSTRACT FROM AUTHOR]

In this article we present a relevant strategy for a non-trivial time-programmed release of water-soluble macromolecules from biocompatible μ-containers. The system is based on self-scrolled chitosan acetate (CA) fibers, encapsulated in a poly(dimethylsiloxane) matrix. Mass transfer between a fiber and the external environment takes place via the only opened extremity of the fiber. Fluoroscein isocyanate dextran (FID) is initially deposited at the inner surface of the CA fiber according to a programmed pattern. The FID molecules became mobile after the arriving of the swelling front, which propagates along the fiber's axis upon the immersion of the system in aqueous solution. Diffusion of the macromolecules into the environment is enabled by the open-tube geometry of the swollen part of the fiber, while a programmed kinetics of the drug release is due to patterning of the polymer film prior to rolling. The release of the macromolecules can be retarded by a few hours according to the placement of the FID spot with respect to the fibers orifice. A pulsatile release kinetics is demonstrated for a discrete pattern. A few millimeter spacing of the FID spots results in a few hours time interval between the release impulses. Random walk model is plugged in the effective diffusion coefficient for Fick's law and the release kinetics are simulated. [ABSTRACT FROM AUTHOR]

The objective of our investigation was to design a thermo-dynamically stable microemulsion formulation of the model drug piroxicam with minimum surfactant concentration in order to improve its solubility. The solubility of piroxicam in different oils was examined. Effects of the co-surfactant:surfactant ratio and water content on microemulsion formulation were evaluated. Phase studies were performed for systems composed of oleic acid as the oil phase, Tween-80 as surfactant, and propylene glycol as co-surfactant at a constant percentage of water to elucidate the effect of microemulsion components on the area of microemulsion formulation. The viscosity and conductivity of certain microemulsion formulations were examined as a function of water dilution. The results showed that oleic acid, Tween-80, and propylene glycol resulted in the highest solubilization of piroxicam. The amount of water that was successfully incorporated into a microemulsion system was directly proportional to the co-surfactant:surfactant ratio and inversely proportional to the percentage amount of the oil phase present in the system. Microemulsion systems displayed changes in their viscosity and conductivity upon water dilution. The pre-microemulsion systems could be used as solvents to provide enhanced solubilizing capacity and stabilization for the solubilized drug. These systems could be loaded with the drug and stored in their original form in order to produce a microemulsion containing the drug in situ upon aqueous dilution. The incorporation of piroxicam in microemulsion formulations led to enhancement of the piroxicam release profile by allowing constant and regular in vitro release as well as reducing piroxicam's particle size to that suited to a microemulsion. Thus, the usage of a microemulsion technique led to improvement in piroxicam availability, suggesting the potential for technique's use as a topical vehicle for piroxicam delivery. [ABSTRACT FROM AUTHOR]

Abstract: Poly(ɛ-caprolactone) (PCL) microspheres loaded two model compounds (p-nitroaniline and rhodamine B) with different water solubilities were prepared by an s/o/w single emulsion solvent evaporation method. The microspheres morphology was investigated by scanning electron microscopy, drug loading and encapsulation efficiency were calculated. Drug distribution within microsphere matrix was studied by confocal laser scanning microscopy. p-Nitroaniline, as a more hydrophobic compound, distributed more evenly in the matrix, while the more hydrophilic compound rhodamine distributed close to the surfaces of microspheres. The in vitro release profiles therefore were different. This study helps to further understand the drug release mechanism from microsphere matrix, and design effective long-term drug delivery system. [Copyright &y& Elsevier]

Transepidermal drug delivery achieves high drug concentrations at the action site and ensures continuous drug delivery and better patient compliance with fewer adverse effects. However, drug delivery through topical application is still limited in terms of drug penetration. Chitosan is a promising enhancer to overcome this constraint, as it can enhance drug diffusion by opening the tight junctions of the stratum corneum. Therefore, here, we developed a novel chitosan nanosponge (CNS) with an optimal ratio and molecular weight of chitosan to improve drug penetration through skin. To prepare the CNS, two types of chitosan (3 and 10 kDa) were each conjugated with poloxamer 407 using para-nitrophenyl chloroformate, and the products were mixed with poloxamer 407 at ratios of 5:5, 8:2, and 10:0. The resulting mixtures were molded to produce flexible soft nanosponges by simple nanoprecipitation. The CNSs were highly stable in biological buffer for four weeks and showed no toxicity in human dermal fibroblasts. The CNSs increased drug permeability through human cadaver skin in a Franz-type diffusion cell, with substantially higher permeability with 3 kDa chitosan at a ratio of 8:2. This suggests the applicability of the novel CNS as a promising carrier for efficient transepidermal drug delivery. [ABSTRACT FROM AUTHOR]