Transfersomes Research Articles

Topical Delivery of Dual Loaded Nano-Transfersomes Mediated Chemo-Photodynamic Therapy against Melanoma via Inducing Cell Cycle Arrest and Apoptosis.

Melanoma is a malignant skin cancer associated with high mortality rates and drug resistance, posing a significant threat to human health. The combination of chemotherapy and photodynamic therapy (PDT) represents a promising strategy to enhance antitumor efficacy through synergistic anti-cancer effects. Topical delivery of chemotherapeutic drugs and photosensitizers (PS) offers a non-invasive and safe way to treat melanoma. However, the effectiveness of these treatments is often hindered by challenges such as limited skin permeability and instability of the PS. In this study, transfersomes (TFS) were designed to facilitate transdermal delivery of the chemotherapeutic drug 5-Fluorouracil (5-FU) and the PS Imperatorin (IMP) for combined chemo-photodynamic therapy for melanoma. The cytotoxic and phototoxic effects of TFS-mediated PDT (TFS-UVA) were investigated in A375 cells and nude mice. The study also demonstrated that TFS-UVA generated intracellular ROS, induced G2/ M phase cell cycle arrest, and promoted cell apoptosis. In conclusion, this study indicated that 5-FU/ IMP-TFS serves as an effective transdermal therapeutic strategy for chemo-PDT in treating melanoma.

Deformation of transfersomes dispersed in hydrated deep eutectic solvent in stratum corneum

Abstract The deformation of transfersomes (TFs) dispersed in deep eutectic solvents and applied to the stratum corneum (SC) was evaluated by small-angle X-ray scattering. We found that TFs permeated the SC, while the regularity and period of the multilayer structure of TFs deformed significantly, depending on the SC location and the time after application.

Centella asiatica transfersomes and Bergamot essential oil nanoemulsion combined in gel exhibited anti-photoaging effects on UVB-radiated BALB/c mice

Photoaging of skin tissue can result from exposure to ultraviolet B (UVB) radiation. This study developed two nanocarriers Centella asiatica (CA) transfersomes (TF) and Bergamot essential oil (BEO) nanoemulsions (NE) combined in a gel formulation as a drug delivery system, in order to study whether they could synergize to prevent UVB radiation and provide anti-photoaging effects. Nanoencapsulation of CA-TF and BEO-NE were examined for their quality by characterizing their physicochemical properties. An in vivo study evaluated topically applied CA-TF and BEO-NE combination gels biological effect on BALB/c mice before UVB radiation (840 mJ/cm2) for two weeks. Particle size analysis of developed nanocarriers exhibited monodispersed pattern with an average particle size and zeta potential of around 9.64 ± 0.35 nm and −39.86 ± 1.33 mV, respectively. In vivo experiments showed that topically applied CA-TF and BEO-NE combination gel significantly prevented UVB-induced wrinkle formation and skin erythema and inhibited histological damage, including epidermal hyperplasia, collagen fibers, and the destruction of elastic fibers. Additionally, the CA-TF and BEO-NE combination gel reduced UVB-induced oxidative stress by increasing superoxide dismutase (SOD) activity and suppressed lipid peroxidation by decreasing malondialdehyde (MDA) expression as well as inhibiting the expression of UVB-induced pro-inflammatory cytokines include tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6). Moreover, the CA-TF and BEO-NE combination gel increased the type I collagen expression, restoring UVB-induced collagen production and density. Therefore, nanoencapsulation CA-TF and BEO-NE combination gel could synergistically prevent UVB-induced oxidative stress and inflammatory responses.

Lyophilization enhances the stability of Panax notoginseng total saponins-loaded transfersomes without adverse effects on ex vivo/in vivo skin permeation

Transfersomes (TFSs) have been extensively investigated to enhance transdermal drug delivery. As a colloidal dispersion system, TFSs are prone to problems such as particle aggregation and sedimentation, oxidation and decomposition of phospholipids. To enhance the stability of panax notoginseng saponins (PNS)-loaded transfersomes (PNS-TFSs) without adverse influences on their skin permeation, we prepared lyophilized PNS-loaded transfersomes (PNS-FD-TFSs), clarified their physicochemical characteristics and investigated their in vitro drug release, ex vivo skin permeation/deposition and in vivo pharmacokinetics. In this study, a simple, fast and controllable process was developed for preparing lyophilized PNS-TFSs. In the optimized PNS-FD-TFS formulation, sucrose and trehalose were added to the PNS-TFS dispersion with a mass ratio of trehalose, sucrose, and phospholipid of 3:2:1, and the mixture was frozen at −80 °C for 12 h followed by lyophilization at −45 °C and 5 Pa for 24 h. The optimized formulation of PNS-FD-TFSs was screened based on the appearance and reconstitution time of the lyophilized products, vesicle size, and PDI of the freshly reconstituted dispersions. It maintained stable physicochemical properties for at least 6 months at 4 °C. The vesicle size of PNS-FD-TFSs was below 100 nm and homogenous with a polydispersity index of 0.2 after reconstitution. The average encapsulation efficiencies of the five index saponins notoginsenoside R1 (NGR1), ginsenoside Rg1 (GRg1), ginsenoside Re (GRe), ginsenoside Rb1 (GRb1) and ginsenoside Rd (GRd) in PNS-FD-TFSs were 68.41 ± 5.77%, 68.95 ± 6.08%, 65.46 ± 10.95%, 91.50 ± 5.62% and 95.78 ± 1.70%, respectively. The reconstituted dispersions of PNS-FD-TFSs were similar to PNS-TFSs in in vitro release, ex vivo skin permeation, and deposition. The pharmacokinetic studies showed that, compared with the PNS liposomes (PNS-LPS), the PNS-FD-TFS-loaded drug could permeate through the skin and enter the blood rapidly. It can be concluded that the lyophilization process can effectively improve the stability of PNS-TFSs without compromising their transdermal absorption properties.

Transfersome, an ultra-deformable lipid-based drug nanocarrier: an updated review with therapeutic applications.

The application of nanotechnology with integration of chemical sciences is increasing continuously in the management of diseases. The drug's physicochemical and pharmacological characteristics are enhanced by application of nanotechnological principles. Several nanotechnology-based formulations are being investigated to improve patient compliance. One such novel nanocarrier system is transfersome (TFS) and is composed of natural biocompatible phospholipids and edge activators. Morphologically, TFS are similar to liposomes but functionally, these are ultra-deformable vesicles which can travel through pores smaller than their size. Because of their amphipathic nature, TFS have the potential to deliver the drugs through sensitive biological membranes, especially the blood-brain barrier, skin layers, and nasal epithelium. Different molecular weight drugs can be transferred inside the cell by encapsulation into the TFS. Knowing the tremendous potentiality of TFS, the present work provides an in-depth and detailed account (pharmaceutical and preclinical characteristics) of TFS incorporating different categories of therapeutic moieties (anti-diabetic, anti-inflammatory, anti-cancer, anti-viral, anti-fungal, anti-oxidant, cardiovascular drugs, CNS acting drugs, vaccine delivery, and miscellaneous applications). It also includes information about the methods of preparation employed, significance of excipients used in the preparation, summary of clinical investigations performed, patent details, latest investigations, routes of administration, challenges, and future progresses related to TFS.

Development and In Vitro/Ex Vivo Evaluation of Lecithin-Based Deformable Transfersomes and Transfersome-Based Gels for Combined Dermal Delivery of Meloxicam and Dexamethasone.

Transfersomes (TFS) are the promising carriers for transdermal delivery of various low and high molecular weight drugs, owing to their self-regulating and self-optimizing nature. Herein, we report synthesis and characterization of TFS loaded with meloxicam (MLX), an NSAID, and dexamethasone (DEX), a steroid, for simultaneous transdermal delivery. The different formulations of TFS containing varying amounts of lecithin, Span 80, and Tween 80 (TFS-1 to TFS-6) were successfully prepared by thin-film hydration method. The size of ranged between 248 and 273 nm, zeta potential values covering from -62.6 to -69.5 mV, polydispersity index (PDI) values in between 0.329 and 0.526, and entrapment efficiency of MLX and DEX ranged between 63-96% and 48-81%, respectively. Release experiments at pH 7.4 demonstrated higher cumulative drug release attained with Tween 80 compared to Span 80-based TFS. The scanning electron microscopy (SEM) of selected formulations -1 and TFS-3 revealed spherical shape of vesicles. Furthermore, three optimized transfersomal formulations (based on entrapment efficiency, TFS-1, TFS-3, and TFS-5) were incorporated into carbopol-940 gels coded as TF-G1, TF-G3, and TF-G5. These transfersomal gels were subjected to pH, spreadability, viscosity, homogeneity, skin irritation, in vitro drug release, and ex vivo skin permeation studies, and the results were compared with plain (nontransfersomal) gel having MLX and DEX. TFS released 71.72% to 81.87% MLX in 12 h; whereas, DEX release was quantified as 74.72% to 83.72% in same time. Nevertheless, TF-based gels showed slower drug release; 51.54% to 59.60% for MLX and 48.98% to 61.23% for DEX. The TF-G systems showed 85.87% permeation of MLX (TF-G1), 68.15% (TF-G3), and 68.94% (TF-G5); whereas, 78.59%, 70.54%, and 75.97% of DEX was permeated by TF-G1, TF-G3, and TF-G5, respectively. Kinetic modeling of release and permeation data indicated to follow Korsmeyer-Peppas model showing diffusion diffusion-based drug moment. Conversely, plain gel influx was found mere 26.18% and 22.94% for MLX and DEX, respectively. These results suggest that TF-G loaded with MLX and DEX can be proposed as an alternate drug carriers for improved transdermal flux that will certainly increase therapeutic outcomes.

Designing, Optimization and Characterization of Trifluralin Transfersomal Gel to Passively Target Cutaneous Leishmaniasis

Herein, Trifluralin (TFL) laden transfersomes (TFS) were investigated against Cutaneous Leishmaniasis (CL), via localized and targeted dermal delivery of TFL. Designed TFL-TFS were optimized utilizing 23 full factorial design on the basis of desired response factors including Particle size (P.S), Polydispersity index (PDI), TFL entrapment (%EE) and deformability index (DI). Optimized formulation was found to display P.S of 140.3 ± 2.3, PDI of 0.006 ± 0.002, %EE of 86 ± 0.5 and 43.5 ± 1.0 DI. Results of TEM and XRD analysis have shown intact spherical structure of TFL-TFS and alteration in TFL crystallinity, respectively. Moreover, the optimized TFL-TFS were loaded in Carbopol-940 gel to attain protracted skin retention. TFL-TFS were found to exhibit sustain TFL release profile for up to 24 h. Ameliorated skin permeation of TFL-TFS, even in absence of permeation enhancers, has shown its suitability for cutaneous application. Macrophage uptake assay demonstrated higher intracellular penetration, evidenced by intense reddish fluorescence of rhodamine loaded TFS in comparison to rhodamine-solution. In vitro anti-leishmanial assessment was showing 2.86-folds and 3.07-folds decrement in IC50-value of TFL-TFS against L. tropica KWH23 amastigotes and promastigotes, respectively. Percent inhibition assay against intra-macrophage amastigotes demonstrated that 90.87% amastigotes were assassinated at 50 μg/ml concentration of TFL-TFS, in comparison to the plain TFL-solution, exhibiting 54% parasitic killing.

Transdermal Film Loaded with Avanafil Ultra-deformable Nanovesicles to Enhance its Percutaneous Absorption and Bioavailability.

The in vitro dissolution of Avanafil (AVA) is the rate-limiting step for its bioavailability. Also, it undergoes the first-pass metabolism, and its absorption is altered significantly in the presence of food. So, our study aimed to overcome the previous hurdles and improve the AVA bioavailability by its incorporation in the ultra-deformable nanovesicles, transfersomes (TRF), then loading these nanovesicles in transdermal films. The AVA-loaded TRF formulation was optimized using Draper-Lin small composite design (D-LSCD). The optimized AVA-loaded TRF was evaluated for quality attributes and assessed for skin permeation using a fluorescence laser microscope and for pharmacokinetic parameters after topical application on the rats. The optimized AVA-loaded TRF showed a vesicle size of 97.75 nm, a zeta potential of -28.83 mV, and entrapment efficiency of 95.14% with good deformability and release profile. The intense discoloration in the deep skin layers of the rats indicated the permeation efficiency of AVA-loaded TRF films. The pharmacokinetic parameters specified the augmented absorption extent with Cmax of 254.66 ± 8.02 ng/mlversus 70.33 ± 3.05 ng/ml which reflected on the AUC0-inf that has a value of 2050.45 ± 159.14 ng/ml h versus 497.34 ± 102.61 ng/ml h for the optimized AVA-loaded TRF film and raw AVA-loaded film, respectively. These promising results wide open the field for broader clinical application of this alternative delivery pathway for superior bioavailability, efficacy, and patient compliance and satisfaction.

Improving Dermal Delivery of Rose Bengal by Deformable Lipid Nanovesicles for Topical Treatment of Melanoma

Cutaneous melanoma is one of the most aggressive and metastatic forms of skin cancer. However, current therapeutic options present several limitations, and the annual death rate due to melanoma increases every year. Dermal delivery of nanomedicines can effectively eradicate primary melanoma lesions, avoid the metastatic process, and improve survival. Rose Bengal (RB) is a sono-photosensitizer drug with intrinsic cytotoxicity toward melanoma without external stimuli but the biopharmaceutical profile limits its clinical use. Here, we propose deformable lipid nanovesicles, also known as transfersomes (TF), for the targeted dermal delivery of RB to melanoma lesions to eradicate them in the absence of external stimuli. Considering RB’s poor ability to cross the stratum corneum and its photosensitizer nature, transfersomal carriers were selected simultaneously to enhance RB penetration to the deepest skin layers and protect RB from undesired photodegradation. RB-loaded TF dispersion (RB-TF), prepared by a modified reverse-phase evaporation method, were nanosized with a ζ-potential value below −30 mV. The spectrophotometric and fluorimetric analysis revealed that RB efficiently interacted with the lipid phase. The morphological investigations (transmission electron microscopy and small-angle X-ray scattering) proved that RB intercalated within the phospholipid bilayer of TF originating unilamellar and deformable vesicles, in contrast to the rigid multilamellar unloaded ones. Such outcomes agree with the results of the in vitro permeation study, where the lack of a burst RB permeation peak for RB-TF, observed instead for the free drug, suggests that a significant amount of RB interacted with lipid nanovesicles. Also, RB-TF proved to protect RB from undesired photodegradation over 24 h of direct light exposure. The ex vivo epidermis permeation study proved that RB-TF significantly increased RB’s amount permeating the epidermis compared to the free drug (78.31 vs 38.31%). Finally, the antiproliferative assays on melanoma cells suggested that RB-TF effectively reduced cell growth compared to free RB at the concentrations tested (25 and 50 μM). RB-TF could potentially increase selectivity toward cancer cells. Considering the outcomes of the characterization and cytotoxicity studies performed on RB-TF, we conclude that RB-TF represents a valid potential alternative tool to fight against primary melanoma lesions via dermal delivery in the absence of light.

TOPICAL DELIVERY OF QUERCETIN LOADED TRANSFERSOMES FOR WOUND TREATMENT: IN VITRO AND IN VIVO EVALUATION

Objective: To design topical Quercetin (Qc)-loaded transfersomes (TFs) for wound treatment. Methods: Qc-loaded TFs were prepared by thin-film hydration technique using 2241full factorial design and the optimum formula was selected. In vivo skin, deposition and cutaneous wound induction studies were performed for four groups of male wistar rats. At the end of the experiment, biochemical parameters were measured in the healed tissues (total proteins (TP), total antioxidant capacity (TAC), glutathione reductase (GSH), nitric oxide (NO), and malonaldehyde (MDA). Two in vivo histopathological experiments using male wistar rats were performed; the first study was done for the healed tissues of the above experiment and the second was to confirm the safety of formulations. Results: Qc optimum TFs (F6) showed EE% of 91.1%, PS of 695.35 nm, PDI of 0.592, and ZP of-11.1 mV, and spherical shape. In vivo skin deposition study showed that drug percentage retained in the skin from Qc optimum TFs was significantly higher than that from Qc suspension and Qc liposomes (p<0.05). There was no significant difference in the values of TP, TAC and MDA between the treated groups (p>0.05). GSH in TFs treated groups was significantly higher than the other groups (p<0.05) while NO in TFs treated groups was significantly lower than the other treated groups (p<0.05). Histopathological experiments showed that wounds treated by TFs healed better than those treated by both liposomes and Qc suspension. Conclusion: Qc-loaded TFs can be used as successful drug-delivery system for wound healing.

Transfersomes improved delivery of ascorbic palmitate into the viable epidermis for enhanced treatment of melasma

Ascorbic palmitate (AP) is widely used in the topical pharmaceutical or cosmetic formulations for melasma treatment. However, the presence of the skin barriers makes it difficult for the highly lipophilic drug molecules to traverse the stratum corneum (SC) and diffuse into the viable epidermis (EP) to reach the melanocytes, thereby exerting suboptimal antimelasma effects. Herein, AP was encapsulated into the transfersomes (TFs), yielding AP-TFs. AP-TFs utilized the deformability of TFs to squeeze through the skin pores in the SC under the transepidermal hydration gradient forces, leading to 14.1-fold increase in AP accumulation to the EP. AP-TFs could slowly release the encapsulated AP, while whether the released AP or transfersomal AP showed comparable uptake into the melanocytes, thereby exerting similar inhibitory effects on tyrosinase activity and melanogenesis. Ultimately, in the rat melasma model, AP-TFs showed superior antimelasma efficacy to free AP, with effective relief of oxidative stress and inflammation in the skin. Moreover, AP-TFs did not induce skin irritation. Therefore, the study provides a safe and effective approach to elevating the delivery of highly lipophilic drugs to the EP for enhanced treatment of melasma.

In vitro and in vivo evaluation of an ionic sensitive in situ gel containing nanotransfersomes for aripiprazole nasal delivery

In the current study, a composite in-situ gel formulation containing aripiprazole (APZ) loaded transfersomes (TFS) was developed for the intranasal brain targeting of APZ. APZ loaded TFS were prepared by applying the film hydration method and optimized using an irregular factorial design. The prepared formulations were optimized based on different parameters including particle size, polydispersity index (PdI), zeta potential, encapsulation efficiency (EE) and release efficiency (RE). The optimized APZ-TFS were distributed in an ion-triggered deacetylated gellan gum solution (APZ-TFS-Gel) and evaluated in terms of pH, gelling time, rheological properties and in-vitro release study. The therapeutic efficacy of the best APZ-TFS-Gel was then tested in the mice model of schizophrenia induced by ketamine by evaluating various behavioral parameters. The optimized formulation showed the particle size of 72.12 ± 0.72 nm, the PdI of 0.19 ± 0.07, the zeta potential of −55.56 ± 1.9 mV, the EE of 97.06 ± 0.10%, and the RE of 70.84 ± 1.54%. The in-vivo results showed that compared with the other treatment groups, there was a considerable increase in swimming and climbing time and a decrease in locomotors activity and immobility time in the group receiving APZ-TFS-Gel. Thus, APZ-TFS-Gel was found to have desirable characteristics for therapeutic improvement.

A COMPARATIVE ASSESSMENT OF VESICULAR FORMULATIONS: TRANSFERSOMES AND CONVENTIONAL LIPOSOMES LOADED IVABRADINE HYDROCHLORIDE

Objective: Ivabradine hydrochloride (IH), a benzazepine derivative used to treat cardiovascular disease angina pectoris. In this study IH-loaded novel carrier systems transfersomes (TFs) and conventional liposomes (CLs) were developed and compared for their efficacy to enhance the stability of drugs from degradation.
 Methods: TFs formulations (TF-1, TF-2 and TF-3) were prepared by using different biocompatible surfactants; tween-80 (TW), span-80(S) and sodium deoxycholate (SC) in the concentration ratio of 15 parts with 85 parts of soy phosphatidylcholine as phospholipid by thin-film hydration method. These vesicles were compared with CLs formulation (L-1) prepared in 7:3 molar ratio of soy phosphatidylcholine: cholesterol by following the same method. These vesicles were compared for physical appearance, vesicle shape, and size, percentage drug entrapment efficiency (%DEE), deformability index (DI), in vitro percentage cumulative drug release study, and physical stability studies. The chosen optimized novel carriers were observed under scanning electron microscopy.
 Results: The compared data demonstrated that the physical appearance for all vesicles was turbid and had a spherical shape. The size distribution was in the range of 129.0 nm to 273.5 nm in vesicles. The %DEE (79.0±0.94) and DI (35.0±1.9) was found maximum in TF-1 formulation that was 2.3 times higher than L-1 formulation. The in vitro percentage cumulative drug release study followed second-order polynomial kinetics that was 2.0 times higher than L-1and 2.9 times higher than the plain drug in 30 min (90.4±0.06%) from TF-1. The vesicles were found to be stable at refrigeration conditions.
 Conclusion: Thus, amongst of all vesicles TW loaded TFs (TF-1) was chosen as an excellent novel vesicular carrier for hydrophilic drugs due to its higher deformability behavior than CLs that protects the certain drugs from biodegradation and provides stability.

FORMULATION AND EVALUATION OF IVABRADINE HYDROCHLORIDE LOADED TRANSFERSOMAL GEL FOR TRANSDERMAL DELIVERY

Objective: Aim of this study was to develop the topical delivery containing ivabradine hydrochloride (IVH) loaded transpersonal gel for symptomatic treatment of chronic stable angina pectoris in coronary artery disease.
 Methods: Different hydrophilic-lipophilic balance (HLB) values of surfactants-tween-80, span-80 and sodium deoxycholate (SDC) were investigated to prepare transfersomes (TFs)respectively, with different concentration of soya phosphatidylcholine and 10% v/v ethanol in phosphate buffer solution (pH 6.8) by conventional rotary evaporation sonication method. The prepared formulations were evaluated for percentage entrapment efficiency (%EE), deformability index (DI), turbidity, vesicle shape and size, in vitro drug release study and stability. SEM was done on selected formulation F8 and liposome formulation (LF). Gel was prepared by using carbopol-940 as a gelling agent with propylene glycol, polyethylene glycol solution as permeation enhancer by 32 factorial design optimization methods. The developed gel was evaluated for pH, viscosity, drug content, ex-vivo permeation studies and stability studies of TFs-gel. This was compared with LF-gel prepared by same procedure.
 Results: Maximum % EE (78.4±0.94), suitable vesicular size (128.6 nm) and maximum DI (34.9±1.9) was found in TFs-TW-80 and selected for gel development. In vitro drug release data from TFs-TW-80, plain drug solution and liposomal formulation (LF) revealed that % cumulative drug released in TFs-TW-80 was found maximum (89.5±0.12 %) in 20 min than others. It was 2.1 times higher than LF and 3.3 times higher than the plain drug. SEM study showed spherical shape of vesicles. The drug contents in the TFs and LF gels were found to be 92 to 95%w/w. Partition coefficient for TFs-loaded gel was 1.04±0.03. Ex vivo permeation study from hairless rat skin showed that permeation of drug is described by firstly first-order kinetics than zero-order kinetics. The drug released from TFs-gel was found to be 1.7 times higher than LF-gel and about 1.9 times higher than plain drug. Flux from TFs-gel was 2.04 times greater than LF-gel and 3.28 times more than plan drug. Stability studies indicated that suitable storage condition for developed gel was temperature 25 °C or less, where the pH, potency and therapeutic efficacy of formulations remain constant.
 Conclusion: Thus, transdermal route has become one of the most successful and innovative focus for research in drug delivery of IVH loaded TFs-TW-80 to increase stability and bioavailability.

Application of Nanopharmaceutics for Flibanserin Brain Delivery Augmentation Via the Nasal Route.

Flibanserin (FLB) is a nonhormonal medicine approved by the Food and Drug Administration (FDA) to treat the hypoactive sexual appetite disorder in females. However, the peroral administration of the medicine is greatly affected by its poor bioavailability as a result of its extensive first-pass effect and poor solubility. Aiming at circumventing these drawbacks, this work involves the formulation of optimized FLB transfersome (TRF) loaded intranasal hydrogel. Box–Behnken design was utilized for the improvement of FLB TRFs with decreased size. The FLB-to-phospholipid molar ratio, the edge activator hydrophilic lipophilic balance, and the pH of the hydration medium all exhibited significant effects on the TRF size. The optimized/developed TRFs were unilamellar in shape. Hydroxypropyl methyl cellulose based hydrogel filled with the optimized FLB TRFs exhibited an improved ex vivo permeation when compared with the control FLB-loaded hydrogel. In addition, the optimized TRF-loaded hydrogel exhibited higher bioavailability and enhanced brain delivery relative to the control hydrogel following intranasal administration in Wistar rats. The results foreshadow the possible potential application of the proposed intranasal optimized FLB-TRF-loaded hydrogel to increase the bioavailability and nose-to-brain delivery of the drug.

Coarse-grained molecular dynamics simulations of the effect of edge activators on the skin permeation behavior of transfersomes

Transfersomes (TRS) can provide sustained drug delivery and themselves are biocompatible, biodegradable and nontoxic. Edge activators (EAs) are key factors for increasing the deformability of TRS, and this active deformation mechanism is of commercial interest, especially at the molecular level. Accordingly, in this paper, the deformability of pure dipalmitoyl phosphatidylcholine (DPPC) vesicles, TRS with sodium cholate as an EA, and DPPC vesicles containing pogostone (POG) were compared via umbrella sampling technology. The DPPC conformation and membrane fluidity of these three types of bilayer systems were evaluated, and the changes in the membrane properties of vesicles caused by EAs were studied. EAs could increase the deformability of TRS by decreasing the deformation energy barrier due to their amphiphilic structures, which was similar to those of DPPC molecules. The membrane properties also changed via treatment with EAs including altering the tail chain angle, disturbing the ordered tail chain arrangement and prompting lateral diffusion of DPPC molecules. In addition, the impact of EAs on DPPC bilayers was further demonstrated to be concentration dependent. An ideal concentration was identified for the lowest amount of EA that offered a gel-liquid-crystalline phase transition of DPPC bilayers. Importantly, POG, a lipophobic transdermal drug, can also affect the skin permeation behavior of vesicles but had weaker effects than EA.

Flexible nano-sized lipid vesicles for the transdermal delivery of colchicine; in vitro/in vivo investigation

Colchicine (CL) is the most effective treatment of acute gout, however, it is associated with side effects in 80% of the patients at therapeutic doses, in addition, it's a water-soluble strong base (pKa ∼12.8) which ionizes at physiological gastrointestinal pH resulting in low oral bioavailability of 44%. This work employed enhancing the bioavailability and reducing the side effects of CL through combining the benefits of the transdermal route together with those of elastic lipid nano-vesicles. Transfersomes (TRs) have been studied as vehicles for transdermal drug delivery, however, poor encapsulation of drugs and drug leaking of the vesicles required complexation of CL with β-cyclodextrin (β-CD) before formulation. The composition of the designed CL-β-CD-TR was studied to balance the flexibility of the vesicles to their entrapment ability. CL-β-CD-TR were characterized for their shape, size, entrapment efficiency, elasticity, release profile, ex vivo skin permeation, pharmacological efficacy, and histopathological effect. Encapsulation efficiency of CL-β-CD complex in the vesicular formulations ranged from 42.3% to 93.8%. Particle size ranged from 70.6 nm to 138.5 nm and zeta potential ranged from 16.1 mV to 23.4 mV. The in vitro release of CL from the selected CL-β-CD-TR formulation (F3) showed a controlled, biphasic profile. Ex vivo study reported the great potential of F3 (CL-β-CD-TR) for skin permeation. In vivo experiment demonstrated that F3 (CL-β-CD-TR) possessed high biological efficacy with reduced skin irritation.

Transfersomal Nanoparticles for Enhanced Transdermal Delivery of Clindamycin

The aim of this work was to study the potential of delivering clindamycin phosphate, as an efficient antibiotic drug, into a more absorbed, elastic ultradeformable form, transfersomes (TRSs). These vesicles showed an enhanced penetration through ex vivo permeation characters. TRSs were prepared using thin-film hydration method. Furthermore, they were evaluated for their entrapment efficiency, size, zeta potential, and morphology. Also, the prepared TRSs were converted into suitable gel formulation using carbopol 934 and were evaluated for their gel characteristics like pH, viscosity, spreadability, homogeneity, skin irritation, in vitro release, stability, and ex vivo permeation studies in rats. TRSs were efficiently formulated in a stable bilayer vesicle structure. Furthermore, clindamycin phosphate showed higher entrapment efficiency within the TRSs reaching about 93.3% ± 0.8 and has a uniform particle size. Moreover, the TRSs surface had a high negative charge which indicated the stability of the produced vesicles and resistance of aggregation. Clindamycin phosphate showed a significantly higher in vitro release (p < 0.05; ANOVA/Tukey) compared with the control carbopol gel. Furthermore, the transfersomal gel showed a significantly higher (p < 0.05; ANOVA/Tukey) cumulative amount of drug permeation and flux than both the transfersomal suspension and the control carbopol gel. In conclusion, the produced results suggest that TRS-loaded clindamycin are promising carriers for enhanced dermal delivery of clindamycin phosphate.

DESIGN AND CHARACTERIZATION OF TRANSFEROSOMAL GEL OF REPAGLINIDE

The main aim of current investigation is to formulate and evaluate transferosomal gel for effective transdermal delivery of r epaglinide. Repaglinide is an oral anti hyperglycemic agent used for the treatment of non - insulin - dependent diabetes mellitu s ( NIDDM ). The pre formulation study was carried out initially in terms of identification (physical appearance, melting point and IR spectra), solubility study and λ max determination. The transfer somes were formulated by modified hand shaking method using surfactant such as Span 80 and Tween 80 in various concentrations and evaluated for their vesicle shape and type, entrap ment efficiency, % drug content and In vitro drug permeation study. The shapes of most repaglinide containing transfer somes were found to be spherical fro m SEM analysis. The % entrapment efficiency of deformable vesicles formulations were found to be in the range of 82.51 % to 87.69 %. Entrapment efficiency of the RT6 formulation was high (maximum 87.69 %). In - vitro skin permeation study studies showed that , transfersome gels were found to increase the skin permeation and deposition showing a controlled effect. Stability studies were performed for RT - 6 Transferosomes to study effect of different temperature conditions on percent entrapment and optimized gel formulation to study content uniformity and physical appearance for a period of 3 months respectively. Finally, in light of the current data, it can be concluded that transferosomes were a promising candidate for t ransdermal delivery, to prolong the releas e and to improve the site specificity of the drug repaglinide.

Development of tacrolimus-loaded transfersomes for deeper skin penetration enhancement and therapeutic effect improvement in vivo

The aims of this study were to prepare novel transfersomes (TFs) for tacrolimus to treat atopic dermatitis, and to observe the therapeutic effects on mice atopic dermatitis, as compared to commercial tacrolimus ointment (Protopic®) and liposomes-gel. Different kinds of surfactants—sodium cholate, Tween 80 and Span 80 were investigated to prepare TFs respectively. TFs-Tween 80 was selected as the optimal carrier owing to the best deformability and the highest drug retentions. Entrapment efficiency and diameter were also evaluated. The optimized TFs were further made into gel and in vitro drug release of TFs-gel after 24 h was higher than the commercial ointment. Cumulative drug release from TFs-gel after 12 h in vitro was 37.6%. The optimized TFs-gel illustrated remarkably highest drug skin retentions when compared with liposomes-gel and commercial ointment in vivo skin retention experiments. The amounts of tacrolimus in epidermis and dermis from TFs-gel were 3.8 times and 4.2 times respectively as much as ointment, while liposomes-gel was only 1.7 times and 1.4 times respectively as compared to ointment. Topical application of TFs-gel displayed the best therapeutic effect on mice atopic dermatitis induced by repeated topical application of 2,4-dinitrofluorobenzene. Thus TFs displayed superior performance and effective skin target for topical delivery of tacrolimus.