Elastic Vesicles Research Articles

Double-mode relaxation of highly deformed anisotropic vesicles.

Lipid vesicles are known to undergo complex conformational transitions, but it remains challenging to systematically characterize nonequilibrium membrane dynamics in flow. Here, we report the direct observation of anisotropic vesicle relaxation from highly deformed shapes using a Stokes trap. Vesicle shape relaxation is described by two distinct characteristic timescales governed by the bending modulus and membrane tension. Interestingly, the fast double-mode timescale is found to depend on vesicle deflation or reduced volume. Experimental results are well described by a viscoelastic model of a deformed membrane. Overall, these results show that vesicle relaxation is governed by an interplay between membrane elastic moduli, surface tension, and vesicle deflation.

What's new in the field of phospholipid vesicular nanocarriers for skin drug delivery.

Over the last three decades, research in the field of phospholipid nanocarriers as tools to improve dermal and transdermal drug delivery has grown substantially. In particular, liposomes have been the target of studies aimed at reformulating vesicles with a greater ability to deliver drugs trans-dermally. A number of additives with varied physicochemical properties have been combined with traditional components of liposomes. These novel modification processes have produced new classes of vesicles with the potential to enhance the treatment of both dermatological disorders and systemic pathologies. Development of the first deformable and elastic phospholipid vesicles has highlighted the key role of vesicle composition in promoting release of vesicle content into and through the skin. This paper discusses the key vesicle properties and mechanisms of delivery by which newly developed phospholipid vesicles can improve percutaneous drug delivery.

Elastic Bilayer Vesicles of Flurbiprofen for Transdermal Delivery: Development and In-Vitro Characterization

Objective: The purpose of the present study was to develop a novel elastic bilayer vesicle entrapped with Flurbiprofen (FLB) for transdermal use to avoid adverse effect associated with oral administration of the drug. Encapsulation of drug in vesicle prolongs the existence of the drug in the systemic circulation and thus enhances penetration into the target site and reduces toxicity. Method: Niosomes were prepared using surfactants (span 40 and span 60) and cholesterol in the molar ratio of 1:1, 2:1, 3:1 and 3:2. Vesicles prepared by thin film hydration method were characterized for morphology, vesicle size and zeta potential, thermal analysis and Entrapment Efficiency (EE). Results: Results revealed that the EE and size of niosomes were influenced by surfactant type and cholesterol ratio. F8 (span 60: cholesterol in 3:2) exhibited the highest encapsulation of FLB (76.77 ± 0.55) with vesicle size of 154 ± 2.96 nm and Polydispersity Index (PDI) of 0.09. The optimized formulation F8 was selected for incorporation into the gel. Niosomal gel was evaluated for homogeneity, pH, spreadability and in-vitro drug release. Conclusion: All the parameters of niosomal gel were found to be satisfactory and in-vitro release study revealed prolonged and complete release of entrapped FLB (93.23±0.65%) in comparison to FLB hydrogel (42.65±0.29%). The results suggested that niosomes may serve as promising vehicles for the transdermal delivery of FLB.

Efficacy of Gelling Agents on the In-vitro Release and Physical Properties of Loxoprofen Sodium Gel Containing Ultra Elastic Vesicles

Objective: Preparation of a topical prolong release gel for loxoprofen sodium using optimized nano-sized transfersome dispersion using different gelling agents with in vitro and in vivo evaluation in comparison to the marketed gel prepared by a conventional method. Method: The optimum nano transfersome dispersion containing 5% egg lecithin (as an oil phase) 1% span 60 (as an emulsifying agent) was converted into a gel using different gelling agents including carbopol 974p, carbopol 940, carbopol 934 and hydroxyl propyl methylcellulose (HPMC K100) at ratio of (1:1). Each prepared gel was then evaluated in vitro to determine the homogenisity, consistency, spreadability, viscosity, and in vitro drug release as well as skin permeation test, human skin irritation test, and in vivo effectiveness. Result: The selected gel formula (TG3) showed best homogenisity, consistency and spreadability as well as it produced initial burst release of 60.3% (within 1 hour) followed by the prolonged release of 95.4% continued for 6 hours. In addition, the optimum gel formula (TG3) has shown remarkable prolong release, which was significantly higher than the marketed gel (loxonin® gel 1%) without any sign of skin irritation with better effectiveness Conclusion: This work succeeded in preparing topical gel for loxoprofen sodium using carbopol 974p as gelling agent and utilizing ultra elastic lipid vesicles (transfersomes) with prolong release that reduces dose frequency and improves patient compliance

Nanomechanical characterization of pressurized elastic fluid nanovesicles using indentation analysis

Mechanical properties play fundamental roles in regulating the biological behaviors of nanovesicles in a wide range of implications including cell uptake, intercellular communication and developing nanocarriers for drug delivery. Here we theoretically probe the mechanical properties of nanovesicles using indentation analysis based on a minimal model fully accounting for both small and large indentation without introducing unphysical contact and geometrical conditions. Two types of vesicles are considered: one having a fixed area and the other undergoing areal stretch. The indentation response of pressurized elastic fluid vesicles depends on the membrane bending rigidity, osmotic pressure, adhesion energy and size of the indenter tip. Moreover, the osmotic pressure dominates the indentation response, effective stiffness and Young’s modulus for strongly pressurized vesicles. An analytical and universal relation which offers a new and easy way to determine the osmotic pressure from the measured indentation force–depth curve is identified. Effects of the nanovesicle size on the effective stiffness at finite and zero osmotic pressures are analyzed and show significantly different trends. Further discussion is made on the differences between the indentation of fluid vesicles and solid thin shells.

Enhanced stability of phenylethyl resorcinol in elastic vesicular formulations

Purpose: To enhance the stability and reduce photo-degradation of phenylethyl resorcinol (PR) by elastic vesicle formation.Methods: PR solution was stored at different temperatures, pH conditions, and under protected and unprotected natural light. The color of the solution and total active content were investigated. Three types of elastic vesicles, viz, ethosomes, transfersomes and invasomes, were prepared and their sedimentation in formulations and total active content were investigated before and after storage under various conditions for 4 months. The stability of the solutions and vesicular formulations were assessed.Results: PR solution was unstable at pH 9, higher temperature (70 ± 1 oC) and under natural light. The color of PR solution changed from colorless to orange tone and the PR content decreased. On the other hand, PR entrapped within ethosome, tranfersome and invasome vesicles showed better stability, color change was not observed in the formulations, and PR content remained > 90 %.Conclusion: All the vesicles display reduced degradation of PR under thermal and natural light. Thus, PR vesicular formulation enhances stability and improves the quality of the product for use in topical administration.Keywords: Phenylethyl resorcinol, Degradation, Ethosomes, Transfersomes, Invasomes, Topical administration

Potential role of resveratrol-loaded elastic sorbitan monostearate nanovesicles for the prevention of UV-induced skin damage

This study was aiming to improve the effect of the water-insoluble drug, resveratrol, by encapsulating it in surfactant-based elastic vesicles (spanlastics). Spanlastics (SLs) were prepared by thin film hydration method using different ratios of Span 60 (S60) and edge activators (EAs). The prepared SLs were subjected to full in-vitro evaluation. All the SLs showed improved properties compared to the drug suspension (p < 0.05). SL5 composed of S60: Brij 35 (7:3) attained the highest drug entrapment efficiency (79.10%±5.56), the smallest particle size (201.30 nm ± 2.45), the best in-vitro anti-oxidant effect and a fast drug release pattern, thus was selected for further investigation. Based on the Draize test, the selected spanlastics (SL5), as well as the drug suspension, showed to be safe to be applied on the skin (PII <2). In-vivo studies were done to test the photoprotective effect of the designed nanovesicles compared to the drug suspension. Evaluation was done based on visual examination and analysis of some anti-oxidant markers (CAT, GSH and SOD), anti-inflammatory markers (IL-6, IL-8 and NF-κB) and anti-wrinkling markers (MMP-1 and GM-CSF) after UVB-irradiation. The drug showed a good prophylactic effect, however, that of SL5 was superior compared to that of the drug suspension as recorded by the level of all biochemical markers (p < 0.05). These results were also confirmed by histopathological examination. This study proves that elastic nanovesicles seem to be a promising approach to overcome the low drug solubility and to improve its efficacy.

Enhanced skin targeting of retinoic acid spanlastics: in vitro characterization and clinical evaluation in acne patients

Acne vulgaris is the most common dermatological disorder affecting millions of individuals. Acne therapeutic solutions include topical treatment with retinoic acid (RA) which showed a good efficacy in treatment of mild and moderate cases. However, the high prevalence of adverse events, such as skin dryness, shedding and skin irritation affects the patient convenience and obstruct the acne treatment. Thus, the objective of this paper was to produce Span 60 based elastic vesicles enriched with penetration enhancers, and study their influence on the delivery of RA and its skin irritation. RA-loaded nanovesicles, enriched with Transcutol®/Labrasol®, were made using the thin film hydration technique, and assessed for entrapment efficiency, particle size and zeta potential. The optimized RA-loaded nanovesicles (composed of Span 60-Tween 20, and Transcutol®) were morphologically assessed via transmission electron microscopy. Moreover, RA deposition into newborn mice skin was assessed in vitro under non-occlusive conditions, where the optimized RA-loaded nanovesicles showed 2-fold higher RA deposition in the skin compared to the corresponding one lacking Transcutol. The optimized RA-loaded nanovesicles incorporated into 1% carbopol gel was evaluated for in-vivo clinical performance in acne patients, and showed appreciable advantages over the marketed formulation (Acretin®) in the treatment of acne regarding skin tolerability and patient’s compliance.

Transfersomes: a novel technique for transdermal drug delivery

Novel drug delivery systems are now a days is creating a new interest in development of drug deliveries. Vesicular drug delivery system is also a part of these novel drug delivery systems. TDDS is the permeability of the skin, it is permeable to small molecules, lipophilic drug and highly impermeable to the macromolecules and hydrophilic drugs. Recent approaches have resulted in design of two vesicular carriers, ethosomes and ultra flexible lipid based elastic vesicles, transferosomes. Transferosomes have recently been introduced, which are capable of transdermal delivery of low as well as high molecular weight drugs. This offers several potential advantages over conventional routes like avoidance of first pass metabolism, predictable and extended duration of activity, minimizing undesirable side effects, utility of short half life drugs, improving physiological and pharmacological response and have been applied to increases the efficiency of the material transfer across the intact skin, by the use of penetration enhancers, iontophoresis, sonophoresis and use of colloidal carriers such as lipid vesicles (liposomes &amp; proliposomes) and non-ionic surfactant vesicles (niosomes &amp; proniosomes). It is suitable for controlled and targeted drug delivery and it can accommodate drug molecules with wide range of solubility. Due to its high deformability it gives better penetration of intact vesicles. They are biocompatible and biodegradable as they are made from natural phospholipids and have high entrapment efficiency. The preparation variables are depending upon the procedure involved for manufacturing of formulation and the preparation procedure was accordingly optimized and validated. Characterization of transferosomes can be done to know the vesicle size, morphology, drug content, entrapment efficiency, penetration ability, occlusion effect, surface charge, in vitro drug release, in vitro skin penetration etc., It increases stability of labile drugs and provides control release. Transferosomes thus differs from such more conventional vesicles primarily by its softer, more deformable, better adjustable artificial membrane.&#x0D; Keywords: Novel Drug Delivery System, Biocompatible, Characterization, Transferosomes.

Elastic liposomes mediated transdermal delivery of verapamil hydrochloride

The aim of present investigation was to formulate and characterize elastic liposomes as a delivery system for transdermal delivery of Verapamil hydrochloride, a drug having low oral bioavailability (approx 20%), short biological half-life and extensive first pass metabolism.Verapamil hydrochloride loaded elastic vesicles were prepared by a slightly modified extrusion method using soya phosphatidylcholine and span 80(edge activator). Prepared elastic vesicles were characterized for various parameters such as vesicle shape, vesicle size and size distribution, entrapment efficiency, elasticity measurements, stability studies and in vitro skin permeation studies through excised rat skin (Sprague Dawley) using a locally fabricated Franz diffusion cell. The entrapment efficiency of elastic vesicles was found to be 59.3±3.6%. In vitro skin permeation of verapamil hydrochloride through excised rat skin (Sprague Dawley) revealed that elastic vesicles led to an enhanced transdermal flux (50.2±4.52 mg/cm2/h) of verapamil hydrochloride as compared to liposomes (11.6±2.12mg/cm2/h). Decreased lag time (0.9 h) was also observed in case of elastic liposomes. Our results indicate the feasibility of elastic liposomes for transdermal delivery of verapamil hydrochloride for improved skin permeation.&#x0D; Keywords: Transdermal delivery, Elastic liposomes, Verapamil hydrochloride.&#x0D;

Implementing Central Composite Design for Developing Transdermal Diacerein-Loaded Niosomes: Ex vivo Permeation and In vivo Deposition.

Background: Niosomes are surfactant-based vesicular nanosystems that proved their efficien-cy in transdermal delivery by overcoming skin inherent anatomic barrier; startum corneum. Central com-posite design is an efficient tool for developing and optimizing niosomal formulations using fewer exper-iments.Objective: The objective of this study was to prepare niosomes as a transdermal delivery system of di-acerein using film hydration technique, employing central composite design, for avoiding its oral gastroin-testinal problems.Methods: Three-level three-factor central composite design was employed for attaining optimal niosomes formulation with the desired characteristics. Three formulation variables were assessed: amount of salt in hydration medium (X1), lipid amount (X2) and number of surfactant parts (X3). DCN-loaded niosomes were evaluated for entrapment efficiency percent (Y1), particle size (Y2), polydispersity index (Y3) and zeta potential (Y4). The suggested optimal niosomes were subjected to further characterization and utilized as a nucleus for developing elastic vesicles for comparative ex vivo and in vivo studies.Results: The values of the independent variables (X1, X2 and X3) in the optimal niosomes formulation were 0 g, 150 mg and 5 parts, respectively. It showed entrapment efficiency percentage of 95.63%, parti-cle size of 436.65 nm, polydispersity index of 0.47 and zeta potential of -38.80 mV. Results of ex vivo permeation and skin deposition studies showed enhanced skin permeation and retention capacity of the prepared vesicles than drug suspension.Conclusion: Results revealed that a transdermal niosomal system was successfully prepared and evaluat-ed using central composite design which will result in delivering diacerein efficiently, avoiding its oral problems.

Combinations of nanovesicles and physical methods for enhanced transdermal delivery of a model hydrophilic drug

Here, we combined lipid nanovesicles (ethosomes, liposomes) as the drug carrier systems with two physical methods (electroporation, sonoporation) to enhance transdermal delivery of a hydrophilic model molecule, calcein. First, using different formulations, ethosomes greatly enhanced calcein permeation by passive diffusion compared to liposomes and calcein in buffer, which is most likely due to a synergism between the ethanol action on the stratum corneum lipids and the penetration of the elastic vesicles. Liposomes permeated poorly through the skin and, as also suggested by other authors, seem to remain confined to the outer layers of the skin. By creating localized effects, liposomes would be better suited to topical dermal delivery than transdermal delivery. Using sonoporation as the physical enhancement method, sonication (5 min) showed improvement over passive diffusion; however, only for the ethosome formulation, and not for solution and liposomes. Similarly, electroporation greatly enhanced delivery of calcein, which was again more pronounced for ethosomes than liposomes and calcein in buffer. Finally, three different transdermal delivery enhancement methods were coupled, using ethosomes as carriers, along with both electroporation and sonoporation, to investigate the potential for synergistic effects. However, these combinations failed to achieve not only synergistic effects, but also additive effects. Nevertheless, combination of the ethosome formulation of calcein with either of electroporation or sonoporation achieves significant enhancement of transdermal molecular delivery being safe for potential clinical use.

Vesicular carriers containing phenylethyl resorcinol for topical delivery system; liposomes, transfersomes and invasomes

Topical administration of phenylethyl resorcinol (PR) has attracted much attention as skin lightening agent with potent anti-tyrosinase activity. Two novel types of elastic carriers were developed to overcome the limitation of PR as topical delivery by increasing the solubility, stability and decreasing skin irritation compared to conventional liposomes. In addition, it also promotes skin penetration of PR to reach deep skin layer at the target site. The lead formulations were obtained from the invasomes containing 1% (w/v) d-limonene mixed with 10% (v/v) absolute ethanol as the skin enhancer, and transfersomes containing 15% (w/w) sodium deoxycholate (SDC) as edge activator. All formulations gave a vesicle size < 500 nm, polydispersity index (PDI) < 0.3, high zeta potential, entrapment efficiency > 50%, and good stability on storage at 30 °C at 75% RH for 4 months. Transfersomes have a lower degree of deformability (6.63%) than invasomes (25.26%). In contrast, the liposomes as rigid vesicles do not show a deformable property. This characteristic affects the skin permeation, and thus, transfersomes with high elastic property provided a significantly higher cumulative amount, steady state flux (Jss) and permeability coefficient (Kp) compared to other formulations. However, in vitro PR accumulation in full-thickness newborn pig skin demonstrated that the application of elastic carrier formulations gave significantly higher accumulation than liposomes, and gave anti-tyrosinase activity up to 80%. These results are straightforwardly related to the results of cellular level study. Transfersomes and invasomes showed higher tyrosinase inhibition activity and melanin content reduction when compared to liposomes in B16 melanoma cells. In addition, acute irritation test in rabbits confirmed that these formulations are safe for skin application. Therefore, elastic vesicle carriers have the efficiency to deliver PR into the deep skin in both quantity and effectiveness which are better than conventional liposomes and appropriate for a skin lightening product.

Combined use of nanocarriers and physical methods for percutaneous penetration enhancement.

Dermal and transdermal drug delivery (due to its non-invasiveness, avoidance of the first-pass metabolism, controlling the rate of drug input over a prolonged time, etc.) have gained significant acceptance. Several methods are employed to overcome the permeability barrier of the skin, improving drug penetration into/through skin. Among chemical penetration enhancement methods, nanocarriers have been extensively studied. When applied alone, nanocarriers mostly deliver drugs to skin and can be used to treat skin diseases. To achieve effective transdermal drug delivery, nanocarriers should be applied with physical methods, as they act synergistically in enhancing drug penetration. This review describes combined use of frequently used nanocarriers (liposomes, novel elastic vesicles, lipid-based and polymer-based nanoparticles and dendrimers) with the most efficient physical methods (microneedles, iontophoresis, ultrasound and electroporation) and demonstrates superiority of the combined use of nanocarriers and physical methods in drug penetration enhancement compared to their single use.

Investigating superiority of novel bilosomes over niosomes in the transdermal delivery of diacerein: in vitro characterization, ex vivo permeation and in vivo skin deposition study

Skin is considered the most accessible organ of the body because of its underlying capillary network. However, stratum corneum (SC), the upper most layer of skin, represents major diffusional barrier for most drugs. Hence, the use of edge activators (EAs) in designing novel elastic vesicles is hypothesized to impart their lipid bilayer with ultra-flexibility to trespass SC by high self-optimizing deformability. To confirm this hypothesis, this work aimed at developing novel bilosomes by modulating conventional niosomal composition using different bile salts as EAs and investigating their superiority over niosomes for transdermal delivery of diacerein (DCN), as model drug. Bilosomes were prepared by thin film hydration (TFH) technique according to full 31.22 factorial design to select the optimal formulation using Design-Expert® software. The optimal bilosomes (B6) showed nanosized vesicles (301.65 ± 17.32 nm) and 100.00 ± 0.00 % entrapment efficiency. Ex vivo permeation studies and in vivo evaluation revealed that B6 exhibited superior permeation and drug retention capacity compared to the conventional niosomal formulation and drug suspension. Furthermore, B6 was subjected to in vivo histopathological study using male Wistar rats which ensured its safety for topical application. Overall, the results confirmed the hypothesized superiority of bilosomes over niosomes for enhancing DCN flux across the skin.

Lubricated immersed boundary method in two dimensions

Many biological examples of fluid–structure interaction, including the transit of red blood cells through the narrow slits in the spleen and the intracellular trafficking of vesicles into dendritic spines, involve the near-contact of elastic structures separated by thin layers of fluid. Motivated by such problems, we introduce an immersed boundary method that uses elements of lubrication theory to resolve thin fluid layers between immersed boundaries. We demonstrate 2nd-order accurate convergence for simple two-dimensional flows with known exact solutions to showcase the increased accuracy of this method compared to the standard immersed boundary method. Motivated by the phenomenon of wall-induced migration, we apply the lubricated immersed boundary method to simulate an elastic vesicle near a wall in shear flow. We also simulate the dynamics of a vesicle traveling through a narrow channel and observe the ability of the lubricated method to capture the vesicle motion on relatively coarse fluid grids.

Ethosomes and Transfersomes: Principles, Perspectives and Practices.

The success story of liposomes in the treatment of systemic infectious diseases and various carcinomas lead the scientists to the innovation of elastic vesicles to achieve similar success through transdermal route. In this direction, ethosomes and transfersomes were developed with the objective to design the vesicles that could pass through the skin. However, there is a lack of systematic review outlining the principles, method of preparation, latest advancement and applications of ethosomes and transfersomes. This review covers various aspects that would be helpful to scientists in understanding advantages of these vesicular systems and designing a unique nano vesicular delivery system. Structured search of bibliographic databases for previously published peer-reviewed research papers was explored and data was culminated in terms of principle of these vesicular delivery systems, composition, mechanism of actions, preparation techniques, methods for their characterization and their application. A total of 182 papers including both, research and review articles, were included in this review in order to make the article comprehensive and readily understandable. The mechanism of action and composition of ethosomes and transfersomes was extensively discussed. Various methods of preparation such as, rotary film evaporation method, reverse phase evaporation method, vortex/ sonication method, ethanol injection method, freeze thaw methods, along with their advantages has been discussed. It was also discussed that both these elastic nanocarriers offer unique advantages of ferrying the drug across membranes, sustaining drug release as well as protecting the encapsulated bio actives from external environment. The enhanced bioavailability and skin penetration of ethosomes as compared to conventional vesicular delivery systems is attributed to the presence of ethanol in the bilayers while that for transfersomes accrues due to their elasticity along with their ability to retain their shape because of the presence of edge activators. Successful delivery of synthetic drugs as well as phytomedicines has been extensively reported through these vesicles. Though these vesicular systems offer a good potential for rational drug delivery, a thoughtfully designed process is required to optimize the process variables involved. Industrial scale production of efficacious, safe, cost effective and stable formulations of both these delivery systems appears to be a pre-requisite to ensure their utility as the trans-dermal vehicles.

Dynamical regimes of lipids in additivated liposomes with enhanced elasticity: A field-cycling NMR relaxometry approach

We study the molecular dynamics of lipids in binary large unilamellar liposomes suspended in D2O composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or soy phosphatidylcholine (SPC) additivated with different percentiles of sodium deoxycholate (SDC). We use the fast field-cycling proton NMR relaxometry technique over a wide timescale and at diverse temperatures. A model previously validated in different formulations is here employed for the relaxometric analysis of elastic vesicles. A new dynamical regime is observed for the first time in additivated DMPC and additivated/non-additivated SPC liposomes. This surprising feature is discussed in terms of vesicle shape fluctuations, enhanced elasticity and lipid & additive diffusion within the membrane. The continuum elastic theory is revisited for a better understanding of recent experiments and those here presented. We address the point of deformability measurements across rigid permeable barriers versus measurements of the bending elastic modulus in free-standing vesicles.

Enhanced non invasive trans-tympanic delivery of ciprofloxacin through encapsulation into nano-spanlastic vesicles: Fabrication, in-vitro characterization, and comparative ex-vivo permeation studies

The aim of this research was to encapsulate ciprofloxacin, a broad spectrum fluoroquinolone antibiotic, into Span 60 based nano-elastic vesicles, nano-spanlastics, for accomplishing improved non invasive trans-tympanic delivery, providing means for ototopical treatment of acute otitis media (AOM). To achieve this purpose, ciprofloxacin-loaded nano-spanlastics were prepared by thin film hydration (TFH) technique, using several non-ionic edge activators (EAs) according to full factorial design (32). The investigation of the effect of formulation variables on nano-spanlastic characteristics and selection of the optimum formula were performed using Design-Expert® software. The selected formulation was also subjected to comparative ex-vivo permeation studies through tympanic membrane (TM) of rabbits. Results revealed that the optimal nano-spanlastic formulation (S-2; containing 20% Brij 35 as an EA) exhibited nano-sized spherical vesicles (287.55±9.97nm), relatively high entrapment efficiency percent (51.81±1.57%), and good physical stability after six months of storage at 4–8°C. Ex-vivo TM permeation studies demonstrated the superiority of the optimal nano-spanlastic formulation over the commercial Ciprocin® drops. However, when compared to lipid-based elastic vesicles, nano-transfersomes, nano-spanlastics exhibited lower drug permeation through the TM. Concisely, the obtained results suggested that nano-spanlastics can be promising for improving trans-tympanic delivery of ciprofloxacin.

Modulation mechanism of the stratum corneum structure during permeation of surfactant-based rigid and elastic vesicles

We evaluated the interaction between human stratum corneum (SC) and surfactant-based rigid or elastic vesicles during permeation using synchrotron X-ray diffraction to obtain the mechanism action of surfactant-based vesicles for enhanced skin permeation. The effects of vesicle elasticity on the interaction with SC were also investigated. Changes in the small-angle X-ray diffraction peaks of the human SC after buffer control and vesicle application were monitored. In the small-angle region, the control as the citrate buffer induced no significant changes of diffraction peaks for the lamellar structure of short periodicity phase (SPP), which is observed as a main peak in the human SC. Application of rigid vesicles resulted in small changes in the diffraction peaks attributed to lamellar phase of SPP. After application of elastic vesicles, however, a large shift to smaller angles due to swelling of the lamellar phase of SPP was clearly observed from the intensity difference profiles. All peaks due to the vesicles were still observed after 2h of application for all formulations, indicating that both vesicles interacted with the SC while maintaining their structures. These results strongly suggest that vesicles affect the lamellar phase of SPP of the intercellular lipids in the SC during permeation.