Ultradeformable liposomes with terpenes for delivery of hydrophilic compound.

Ultradeformable liposomes containing penetration enhancers were created to deliver NaFl. Vesicles were investigated for their particle size, zeta potential, NaFl entrapment efficiency (%EE), loading efficiency, and in vitro skin penetration. The vesicles obtained were spherical in shape, with a particle size of less than 100 nm and a negative surface charge (-6 to -11 mV). The %EE of NaFl loaded in vesicles ranged from 37 to 48%. Ultradeformable liposomes with monoterpenes (d-limonene, 1,8-cineole and geraniol) significantly improved NaFl penetration through the skin. Confocal laser scanning microscopy analysis confirmed skin-penetration results and was used to evaluate the behavior of hydrophilic compounds penetrating through the skin.

Development and Skin Penetration Pathway Evaluation Using Confocal Laser Scanning Microscopy of Microemulsions for Dermal Delivery Enhancement of Finasteride.

This study aimed to develop microemulsions using poloxamer 124 as a surfactant to improve the skin penetration of finasteride and to investigate the skin penetration pathways of these microemulsions by colocalization techniques using confocal laser scanning microscopy (CLSM). The prepared finasteride-loaded microemulsions had average particle sizes ranging from 80.09 to 136.97 nm with particle size distributions within acceptable ranges and exhibited negative surface charges. The obtained microemulsions could significantly increase the skin penetration of finasteride compared to a finasteride solution. According to the skin penetration pathway evaluation conducted with CLSM, the microemulsions were hair follicle-targeted formulations due to penetration via the transfollicular pathway as a major skin penetration pathway. Additionally, this study found that the microemulsions also penetrated via the intercluster pathway more than via the intercellular pathway and transcellular pathway. The intercluster pathway, intercellular pathway, and transcellular pathway were considered only minor pathways.

Development of Ultradeformable Liposomes with Fatty Acids for Enhanced Dermal Rosmarinic Acid Delivery.

This study aimed to develop ultradeformable liposomes (ULs) with fatty acids, namely, oleic, linoleic, and linolenic acid, to improve the skin penetration of rosmarinic acid. This study also investigated the vesicle-skin interaction and skin penetration pathway of ULs with fatty acids using the co-localization technique of multifluorescently labeled particles. The prepared ULs were characterized in terms of size, surface charge, size distribution, shape, % entrapment efficiency (% EE), and % loading efficiency (% LE). The prepared ULs with fatty acids had an average particle size between 50.37 ± 0.3 and 59.82 ± 17.3 nm with a size distribution within an acceptable range and exhibited a negative surface charge. The average % EE and % LE were 9 and 24.02, respectively. The in vitro skin penetration study found that ULs with oleic acid could significantly increase the skin penetration of rosmarinic acid compared to ULs. According to confocal laser scanning microscopy observations, this study suggested that UL vesicles attach to the skin before releasing the entrapped drug to penetrate the skin. These findings suggested that ULs with oleic acid penetrated the skin via the transfollicular pathway as a major penetration pathway.

Combined effect of sonophoresis and a microemulsion on the dermal delivery of celecoxib.

The aim of this study was to evaluate the intensity of sonophoresis at which the skin penetration of celecoxib was enhanced and to study the combined effects of sonophoresis and microemulsion application on the dermal delivery of celecoxib. The sonophoresis intensity that provided the highest skin penetration enhancement of celecoxib was 30 Watts/cm2. However, the combination of sonophoresis and the microemulsion resulted in a decrease in celecoxib skin penetration. The results of a confocal laser scanning microscopy study using the colocalization analysis of multifluorescently labeled particles revealed that the reduction in skin penetration of celecoxib from the combination of sonophoresis and a microemulsion resulted from a decrease in transfollicular penetration, which is the major skin absorption pathway of the microemulsion.

Development and skin penetration pathway evaluation of microemulsions for enhancing the dermal delivery of celecoxib.

This study aimed to develop a microemulsion using PEG-6 Caprylic/Capric Glycerides as a surfactant to enhance the dermal delivery of celecoxib. Confocal laser scanning microscopy (CLSM) using the colocalization technique was also used to investigate the skin penetration pathway of the microemulsion. The prepared microemulsion formulations were characterized in terms of size, surface charge, size distribution and type. The celecoxib-loaded microemulsion had particle sizes ranging from 48 to 214 nm with neutral charge and significantly increased the skin penetration of celecoxib. According to the CLSM study, the microemulsion might attach to any part of the skin before releasing the entrapped drug to penetrate the tissue. The transfollicular pathway might be the major skin penetration pathway for the microemulsion, whereas the intercellular and transcellular pathways are minor ones.

Development and mechanistic study of a microemulsion containing vitamin E TPGS for the enhancement of oral absorption of celecoxib.

Purpose: The purpose of this study was to develop a microemulsion containing D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) as a biodegradable surfactant to increase the oral absorption of celecoxib. Methods: This study investigated the intestinal absorption enhancement mechanism of this microemulsion by measuring transepithelial electrical resistance (TEER) values. This study also evaluated microemulsion particle-intestine interactions in terms of release and attachment processes using confocal laser scanning microscopy (CLSM). Results: The prepared microemulsion particles had a size of <300 nm with a neutral surface charge. The celecoxib-loaded microemulsion release kinetic was classified as the zero-order model. This vitamin E TPGS-based microemulsion significantly increased the in vitro intestinal absorption of celecoxib compared to celecoxib solution. The CLSM study suggested that microemulsion particles with entrapped drugs might attach to the intestinal epithelium before releasing the entrapped drug into tissues. The TEER value of the intestinal tissues treated with the celecoxib-loaded microemulsion was significantly decreased compared to the value before treatment, indicating an increase in drug transport via the paracellular pathway. The evaluation of intestinal tissue cytotoxicity using lactate dehydrogenase cytotoxicity assay suggested that the prepared celecoxib-loaded microemulsion was safe for oral route administration. Conclusions: The prepared celecoxib loaded microemulsion could increase the intestinal absorption of celecoxib compared to celecoxib solution. The intestinal absorption enhancement mechanism of this microemulsion resulted from the increase of the drug transport via the paracellular pathway.

Development of a novel microemulsion for oral absorption enhancement of all-trans retinoic acid.

This study was aimed to develop a novel microemulsion that contained oleth-5 as a surfactant to enhance the oral absorption of all-trans retinoic acid (ATRA). The prepared microemulsion was evaluated for its particle size, shape, zeta potential, in vitro release, in vitro intestinal absorption, intestinal membrane cytotoxicity and stability. The obtained microemulsion was spherical in shape with a particle size of <200 nm and a negative surface charge. The in vitro release of the ATRA-loaded microemulsion was best fit with the zero-order model. This microemulsion significantly improved the intestinal absorption of ATRA. Confocal laser scanning microscopy analysis using a fluorescent dye-loaded microemulsion also confirmed the intestinal absorption result. The intestinal membrane cytotoxicity of the ATRA-loaded microemulsion did not differ from an edible oil (fish oil). Stability testing showed that the ATRA-loaded microemulsion was more stable at 25°C than 40°C.

Effect of liposomal fluidity on skin permeation of sodium fluorescein entrapped in liposomes.

The purpose of this study was to investigate the effect of ultradeformable liposome components, Tween 20 and terpenes, on vesicle fluidity. The fluidity was evaluated by electron spin resonance spectroscopy using 5-doxyl stearic acid and 16-doxyl stearic acid as spin labels for phospholipid bilayer fluidity at the C5 atom of the acyl chain near the polar head group (hydrophilic region) and the C16 atom of the acyl chain (lipophilic region), respectively. The electron spin resonance study revealed that Tween 20 increased the fluidity at the C5 atom of the acyl chain, whereas terpenes increased the fluidity at the C16 atom of the acyl chain of the phospholipid bilayer. The increase in liposomal fluidity resulted in the increased skin penetration of sodium fluorescein. Confocal laser scanning microscopy showed that ultradeformable liposomes with terpenes increase the skin penetration of sodium fluorescein by enhancing hair follicle penetration.

Investigation of the mechanism of enhanced skin penetration by ultradeformable liposomes.

This study aimed to determine the mechanism by which ultradeformable liposomes (ULs) with terpenes enhance skin penetration for transdermal drug delivery of fluorescein sodium, using transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM). Skin treated with ULs containing d-limonene, obtained from in vitro skin penetration studies, was examined via TEM to investigate the effect of ULs on ultrastructural changes of the skin, and to evaluate the mechanism by which ULs enhance skin penetration. The receiver medium collected was analyzed by TEM and CLSM to evaluate the mechanism of the drug carrier system. Our findings revealed that ULs could enhance penetration by denaturing intracellular keratin, degrading corneodesmosomes, and disrupting the intercellular lipid arrangement in the stratum corneum. As inferred from the presence of intact vesicles in the receiver medium, ULs are also able to act as a drug carrier system. CLSM images showed that intact vesicles of ULs might penetrate the skin via a transappendageal pathway, potentially a major route of skin penetration.

Visualization of ultradeformable liposomes penetration pathways and their skin interaction by confocal laser scanning microscopy.

The objective of this study was to elucidate the skin penetration pathway of the generated ultradeformable liposomes (ULs) with terpenes for transdermal drug delivery of fluorescein sodium (NaFl). ULs with d-limonene were selected to investigate the penetration pathways and vesicle-skin interaction in terms of release and attachment processes via Confocal Laser Scanning Microscopy (CLSM). A co-localization technique was employed to visualize the skin penetration behavior of UL-labeled red fluorescence (Rh-PE) and fluorescence-entrapped drug (NaFl) through porcine skin. Our results suggested that ULs with entrapped drug might attach to any part of the skin before releasing the entrapped drug into the skin. Most ULs and entrapped drug penetrated through hair follicles more than through the nonfollicular region. In summary, the transfollicular pathway was the major penetration pathway of ULs with d-limonene for transdermal drug delivery of NaFl, whereas the intercellular and transcellular pathways were the minor penetration pathways.