Potential of Vesicles to Optimize Topically Applied Formulations with Enhanced Skin Penetration of Drugs 2017 (original) (raw)
Related papers
International Journal of Cosmetic Science, 2020
The permeation of hydrophilic molecules through the skin is still a challenge due to the barrier posed by stratum corneum, the outermost layer of the skin. Liposomes have frequently been used as carriers for different types of drugs and may also function as permeation enhancers. Propylene glycol has also been used as an edge activator in liposomes to increase the permeation. The aim of this work was to prepare liposomes containing an edge activator and loaded with caffeine to evaluate the potential of caffeine reaching the deeper layers in the skin. METHODS: The formulations were prepared by a top-down process using high-pressure homogenization at 20000 psi for 10 minutes. They were characterized by size, polydispersity index (PI), zeta potential (ZP), pH, caffeine content, and encapsulation efficiency (EE%) on preparation (time zero) and after 30 days. Cytotoxicity of blank and loaded liposomes was assessed by MTT proliferation assay with a normal keratinocyte cell line (HaCaT). In vitro permeation tests were performed with human skin in Franz cells over 24 h, and caffeine concentration was determined in the skin surface, stratum corneum, dermoepidermal fraction and receptor medium by HPLC. RESULTS: The caffeine liposomes with (DL-Caf) or without propylene glycol (CL-Caf) showed, respectively, mean size 94.5 and 95.4 nm, PI 0.48 and 0.42, ZP +1.3 and +18.1 mV and caffeine content of 78.57 and 80.13%. IC 50 values of caffeine in DL-Caf (3.59 v/v %) and CL-Caf (3.65 v/v %) were not significantly different from conventional blank liposome (3.27 v/v %). The DL-Caf formulation presented the best capability to enhance the caffeine permeation through the skin, Accepted Article This article is protected by copyright. All rights reserved resulting 1.94 folds higher than caffeine solution. Furthermore, the caffeine flux from DL-Caf was 1.56 and 3.05 folds higher than caffeine solution and CL-Caf, respectively. On the other hand, CL-Caf showed the lowest caffeine penetration revealing the importance of edge activator to aid hydrophilic drug penetration to all skin layers. CONCLUSION: The DL-Caf formulation tested was able to improve the permeation of caffeine through the stratum corneum and dermo epidermal layers, suggesting that this delivery system may be effective for deep skin delivery of hydrophilic drugs.
The skin-permeation-enhancing effect of phosphatidylcholine: caffeine as a model active ingredient
Journal of cosmetic science
Phospholipids or liposomes are recognized to have skin permeation enhancing ability, although their mechanisms are still controversial. The aim of this study was to establish a method of increasing the skin permeation of active ingredients, using phosphatidylcholine as a permeation enhancer. Caffeine was used as a model active ingredient and in vitro skin penetration experiments were performed using Franz-type diffusion cells to determine the amount of absorbed caffeine. Lipid vesicles were prepared by the microfluidization process. The encapsulation efficiency of caffeine was found to be very low due to the instability of the liposome structure and the water solubility of caffeine. However, the amount of absorbed caffeine was nearly independent of the encapsulation efficiency and the vesicle size, but increased with the increase of phosphatidylcholine concentration. These results indicated that phosphatidylcholine could act as a penetration enhancer, irrespective of its presence in...
Journal of Drug Delivery Science and Technology
The objective of the present study is to search for a good selection method of phospholipids to design liposome preparations with high skin penetration-enhancing effects. Five kinds of phosphatidylcholines and phosphatidylglycerols each were selected. First, phospholipid aqueous dispersions and liposomes containing caffeine as a model drug were tested for their skin penetration-enhancing effects using excised hairless rat skin. As results, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-dipalmitoyl-sn-glycero-3phosphoglycerol, sodium salt (DPPG) dispersions showed high penetration-enhancing ratio (ER), whereas DPPG, 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) and 1,2dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes showed high ER, suggesting that liposomes had different skin penetration-enhancing mechanisms from phospholipid dispersions. Next, two kinds of experiments were done to clarify the possible mechanism of liposomes as follows: the excised skin was pretreated for 1 h with caffeine-free phospholipid dispersions and liposomes, and caffeine solution was added to determine its skin permeation. Separately, caffeine permeation experiments were done using physical mixture of blank liposomes and caffeine solution (caffeine-spiked liposomes) and caffeine-entrapped liposomes (caffeine was entrapped only in liposomes). As results, DPPG was a promising phospholipid candidate to fabricate liposome formulations with high skin penetration-enhancing effects, since DPPG phospholipid and its liposome vesicles had a combination effect to disrupt the SC lipid barrier as well as could carry both free and entrapped caffeine in the formulation through the skin.
Formulation and penetration enhancement activity of sticks containing caffeine
journal of applied pharmaceutical science, 2018
Caffeine is a methyl xanthine alkaloid that has been widely used in cosmetic products as anti-cellulite. Caffeine has a hydrophilic character, thus it has difficulty in penetrating the lipid layer of the skin. The aims of this study were to formulate sticks containing emulsion and microemulsion caffeine (control stick), caffeine emulsions (emulsion stick), and caffeine microemulsion (microemulsion stick) and compare the penetration between them. Caffeine was made in the form of water in oil emulsions and microemulsion then form into sticks-shaped with the lipophilic component. All sticks were physically and chemically evaluated. The penetration of caffeine through Sprague-Dawley rat skin using Franz Diffusion Cell were tested for 12 hours. The penetration result of caffeine from control stick, emulsion stick, and microemulsion stick were 306.42 ± 34.92 µg/cm2, 927.75 ± 57.38 µg/cm2, and 2408.68 ± 81.65 µg/cm2 respectively, with percentage 5.90 ± 0.67%, 12.76 ± 0.78%, and 35.23 ± 1.1...
Caffeine-Loaded Niosomes: Characterization and in Vitro Release Studies
We prepared different neutral and positively charged niosomal formulations containing sorbitan esters for entrapment of caffeine. Drug entrapment reduced following the incorporation of positively charged molecule. Furthermore, the span 60-containing niosomes showed the highest drug encapsulation efficiency due to solid-state nature of this surfactant's bilayers. There was a regular relationship between lipophilicity (HLB values) of surfactants and mean particle sizes; increasing the HLB value resulted in larger niosomes. By means of diffusion experiments with Franz diffusion cells, the effects of different vesicular components and that of the positive charge on the release of caffeine from various vesicle formulations were studied. Obtained results indicate that a combined erosiondiffusion mechanism regulates the permeation of caffeine through cellulose acetate membranes. High encapsulation efficiency, appropriate size distribution, and good vesicular stability, especially in solid state niosomes, make this type of vesicular systems a good alternative to liposomes for topical delivery of caffeine.
Validation of an In vitro-in vivo Assay System for Evaluation of Transdermal Delivery of Caffeine
Drug Delivery Letters, 2019
Introduction: Degree of skin penetration of topical drugs and cosmetics is a crucial point concerning their effects and tolerability. For testing drug delivery across the dermal barrier different in vitro and in vivo assays have been developed. Caffeine has been shown to have beneficial effects against skin aging, sunburn and hair-loss, and it is protective against melanoma and non-melanoma type skin cancers. Aim of our study was to set up an assay system to evaluate caffeine penetration from topical formulation into the skin. Methods: Franz diffusion cells consisting of either a filter paper or an artificial membrane or rat skin were used as in vitro/ex vivo test systems and transdermal microdialysis in anaesthetized rats was performed as an in vivo assay. Results: Results indicate that Franz diffusion cell studies provide a good approximation of the release of caffeine from the formulation but are not able to differentiate between 2% and 4% cream concentrations. The maximum concen...
Topical delivery of caffeine from some commercial formulations
International journal of pharmaceutics, 1999
Permeation of caffeine through human skin and artificial membranes (mounted in modified Franz type diffusion cells) was evaluated, either from saturated solutions or from commercially available topical formulations (all containing 3% caffeine). Data interpretation of the caffeine diffusion through human skin does not implicate transfer through pores despite caffeine being a relatively polar molecule. No correlation was found between transfer though the synthetic membranes (cellulose acetate impregnated with isopropyl myristate and silicone rubber soaked in isopropyl myristate) and that observed through skin. The synthetic membranes can be used for assessing product performance in quality assurance but will give little indication of its performance in vivo. The study investigated the percutaneous permeation of caffeine through human skin in order to obtain a mechanistic interpretation of its route of permeation. Synthetic membranes were also examined to determine if they could be use...
Transdermal Evaluation of Caffeine in Different Formulations and Excipients
Journal of Caffeine Research, 2013
Background: The stratum corneum (SC) forms a difficult physical barrier for drugs to pass through the skin. Several strategies were developed to overcome this barrier. Optimization of topical drug formulations by selected excipients may facilitate the penetration of drugs through the SC into the viable skin cells and ultimately into the systemic circulation. Methods: Here, both the influence of two formulations (a classic carbomer-based gel and a novel Pluronic Ò lecithin organo gel (PLO gel)) and selected excipients (ethanol, propylene glycol, diethylene glycol monoethyl ether, isopropyl myristate (IPM), and water) with or without the penetration enhancer miconazole nitrate on the transdermal penetration characteristics of caffeine were determined using an in vitro Franz diffusion cell setup. Results: Higher fluxes were observed for the carbomer-based gel compared to the PLO gel. Among the commonly used excipients, IPM showed the best penetration enhancing properties, while the presence of the penetration enhancer miconazole nitrate did not significantly alter the apparent skin permeation characteristics for caffeine. Conclusion: The high ethanol percentage in the carbomer-based gel could explain the results as supported by our excipient data. Moreover, IPM could play a beneficial role in topical formulations as this excipient was responsible for a significant increase in the amount of caffeine penetrated through the skin. No overall statistical significant effect of the presence of miconazole nitrate as a penetration enhancer was observed.
Drug development and industrial pharmacy, 2018
Cellulite is a common topographical alteration where skin acquires an orange peel or mattress appearance with alterations in adipose tissue and microcirculation. This work aims to develop and evaluate a topical niosomal gel formulae with good permeation to reach the subcutaneous fat layer. Several caffeine niosomal dispersions were prepared and incorporated into gel formulae using Carbopol 940 polymer, chemical penetration enhancers, and iontophoresis, then the prepared gels were applied onto the skin of rats and anticellulite activity of caffeine from the prepared gels compared to that of the commercial product Cellu Destockwas evaluated by histological study of the skin and measurement of plasma level of caffeine passing through the skin using liquid chromatography (LC/MS-MS). Results of histology revealed reduction of size and thickness of fatty layer of rat skin in the following order: FVII > FXIV > Cellu Destock > FVII + Iontophoresis > FXIV + Iontophoresis. Pharmac...
Improved Delivery of Caffeic Acid through Liposomal Encapsulation
Journal of Nanomaterials, 2016
Photoageing resulting from long term exposure of the skin to UV light can be minimized by scavenging the reactive photochemical intermediates with antioxidants. For effective photoprotection, the antioxidant must overcome the barrier properties of the skin and reach the target site in significant amounts. The present study aims to improve the skin penetration of caffeic acid, a very effective free radical scavenger, by encapsulating in liposomes. Caffeic acid loaded liposomes prepared using the reverse phase evaporation technique showed 70% encapsulation efficiency and size around 100 nm with zeta potential of −55 mV.In vitrodiffusion through a dialysis membrane enabled 70% release of encapsulated caffeic acid within 7 h, whereas 95% of free caffeic acid diffused within 4 h in PBS solution (pH 7.4). Liposomal caffeic acid permeation through pig skin epidermis in a Franz cell apparatus was 45 % during 7 h. In contrast, free caffeic acid was almost nonpermeable (<5%) to pig skin du...