Overcoming Skin Barrier with Transfersomes: Opportunities, Challenges, and Applications.

BACKGROUND: Transdermal drug delivery systems (TDDS) offer several advantages over traditional methods like injections and oral administration, including preventing first-pass metabolism, providing consistent and sustained activity, reducing side effects, enabling the use of short halflife drugs, improving physiological response, and enhancing patient convenience. However, the permeability of skin poses a challenge for TDDS, as it is impermeable to large molecules and hydrophilic drugs but permeable to small molecules and lipophilic medications. To overcome this barrier, researchers have investigated vesicular systems, such as transfersomes, liposomes, niosomes, and ethosomes. Among these vesicular systems, transfersomes are particularly promising for non-invasive drug administration due to their deformability and flexible membrane. They have been extensively studied for delivering anticancer drugs, insulin, corticosteroids, herbal medicines, and NSAIDs through the skin. Transfersomes have demonstrated efficacy in treating skin cancer, improving insulin delivery, enhancing site-specific corticosteroid delivery, and increasing the permeation and therapeutic effects of herbal medicines. They have also been effective in delivering pain relief with minimal side effects using NSAIDs and opioids. Transfersomes have been used for transdermal immunization and targeted drug delivery, offering site-specific release and minimizing adverse effects. Overall, transfersomes are a promising approach for transdermal drug delivery in various therapeutic applications. OBJECTIVES: The aim of the present review is to discuss the various advantages and limitations of transfersomes and their mechanism to penetration across the skin, as well as their application for the delivery of various drugs like anticancer, antidiabetic, NSAIDs, herbal drugs, and transdermal immunization. METHODS: Data we searched from PubMed, Google Scholar, and ScienceDirect. RESULTS: In this review, we have explored the various methods of preparation of transferosomes and their application for the delivery of various drugs like anticancer, antidiabetic, NSAIDs, herbal drugs, and transdermal immunization. CONCLUSION: In comparison to other vesicular systems, transfersomes are more flexible, have greater skin penetration capability, can transport systemic medicines, and are more stable. Transfersomes are capable of delivering both hydrophilic and hydrophobic drugs, making them suitable for transdermal drug delivery. The developed transfersomal gel could be used to improve medicine delivery through the skin.

Experimental Animal Models: Tools to Investigate Antidiabetic Activity.

About 2.8% of the global population are being suffered from Diabetes mellitus. Diabetes mellitus is a group of metabolic disorders that is characterized by an absolute lack of insulin and resulting in hyperglycemia. To overcome the challenges, many antidiabetic drugs are being used, and research is being carried out in search of more effective anti-diabetic drugs. To study the effectiveness of antidiabetic drugs, many diabetic models, chemicals, and diabetogenic hormones were used at the research level. In this review, we summarised various animal models used, chemicals that induce diabetes, their properties, and the mechanism of action of these models. Further, diabetes mellitus is generally induced in laboratory animals by several methods that include: chemical, surgical and genetic manipulations. To better understand both the pathogenesis and potential therapeutic agents, appropriate animal models of type 1 & type 2 diabetes mellitus are needed. However, for an animal model to have relevance to the study of diabetes, either the characteristics of the animal model should mirror the pathophysiology and natural history of diabetes or the model should develop complications of diabetes with an etiology similar to that of the human condition. There appears to be no single animal model that encompasses all of these characteristics, but there are many that provide very similar characteristics in one or more aspects of diabetes in humans. The use of the appropriate animal model based on these similarities can provide much-needed data on pathophysiological mechanisms operative in human diabetes.

Nanosized ethanol based malleable liposomes of cytarabine to accentuate transdermal delivery: formulation optimization, in vitro skin permeation and in vivo bioavailability.

Cytarabine is a pyrimidine nucleoside analog used predominantly for acute myeloid leukemia (AML) and also for other indications, including acute lymphocytic leukemia, chronic myelogenous leukemia, and lymphoma by parenteral route due to its low oral bioavailability. Parenteral administration requires constant plasma level, monitoring for its fluctuation and poor patients compliances. Hence the objective of this work is to construct optimized nanosized malleable liposomes of cytarabine to accentuate transdermal delivery of drug to circumvent previously mentioned drawbacks. We also investigated its characteristics and therapeutic efficiency and attempted to systematically explore the penetration enhancing property. Well characterized ethanolic liposomes were also biologically tested for dermatological safety and systemic bioavailability. Ethanolic liposomes were found to be spherical having nanometric size with low polydispersity and high encapsulation efficiency. Skin permeation and deposition studies revealed significant enhancement. In vivo, skin irritation study of developed formulation showed no erythema or scaling vis-à-vis the liposomes. Blood profile of this novel formulation indicated lower lag time with the high amount of drug within 3-12 h after transdermal administration demonstrating the enhanced percutaneous penetration of cytarabine with no erythema, thus leading to patient's compliance by alternative delivery of drug for the treatment of leukemia.

Biodistribution and targeting potential assessment of mucoadhesive chitosan nanoparticles designed for ulcerative colitis via scintigraphy.

In the present investigation we have prepared and characterized curcumin (CN)-containing chitosan nanoparticles (CS-NPs) coated with Eudragit FS 30D for colon-specific drug delivery for treatment of ulcerative colitis. METHODS: CS-NPs were prepared by ionic gelation using tripolyphosphate. To specify pH sensitive delivery, CS-CN-NPs were coated with Eudragit FS 30D by using a solvent evaporation method. Different process parameters were evaluated, and the optimized formulation was characterized by particle size, size distribution, zeta potential and encapsulation efficiency before lyophilization. The lyophilized product was further subjected to Fourier-transform infrared spectroscopy, and particle morphology and in vitro drug release in different media were studied. RESULTS: the kinetics of in vitro drug release from the CS-CN-NPs revealed sustained release behaviour of the developed carriers. In vivo biodistribution study by gamma-scintigraphy showed good accumulation of the developed nanocarriers in the colonic region. CONCLUSION: sustained and pH stimulated delivery of CN to the colon was successfully attained via coating of CS-NPs with Eudragit FS 30D to circumvent poor absorption and availability of CN.

Lipid based noninvasive vesicular formulation of cytarabine: Nanodeformable liposomes.

Leukemia is the common cause of death and worldwide incidence of this disease is increasing. Chemotherapy is the first choice for leukemia treatment, but the major limitations of standard therapy are its side effects and poor patient compliances. Therefore it is imperative to look for a therapeutic system with lesser side effects urgently to address the underlying causes of poor treatment outcomes. In such a scenario transdermal route for delivery of chemotherapeutic drugs could be a better alternative to provide sustained drug level, enhanced activity, self administration and better patient compliances. The present work is focus on the design of nanolipid based transdermal carrier, deformable liposomes bearing cytarabine as a model drug for effective delivery of drug with enhanced transdermal flux. Developed nanocarriers were characterized for their size, morphology, entrapment efficiency, skin penetration and irritation. It could be concluded that nanodeformable liposomes accentuated transdermal flux of cytarabine and could provide a new strategy for leukemia.

Nanocarriers Based Anticancer Drugs: Current Scenario and Future Perceptions.

Anticancer therapies mostly depend on the ability of the bioactives to reach their designated cellular and subcellular target sites, while minimizing accumulation and side effects at non specific sites. The development of nanotechnology based drug delivery systems that are able to modify the biodistribution, tissue uptake and pharmacokinetics of therapeutic agents is considered of great importance in biomedical research and treatment therapy. Controlled releases from nanocarriers can significantly enhance the therapeutic effect of a drug. Nanotechnology has the potential to revolutionize in cancer diagnosis and therapy. Targeted nano medicines either marketed or under development, are designed for the treatment of various types of cancer. Nanocarriers are able to reduce cytotoxic effect of the active anticancer drugs by increasing cancer cell targeting in comparison to conventional formulations. The newly developed nano devices such as quantum dots, liposomes, nanotubes, nanoparticles, micelles, gold nanoparticles, carbon nanotubes and solid lipid nanoparticles are the most promising applications for various cancer treatments. This review is focused on currently available information regarding pharmaceutical nanocarriers for cancer therapy and imaging.

Enhanced skin delivery of aceclofenac via hydrogel-based solid lipid nanoparticles.

The aim of the present study was to develop solid lipid nanoparticles (SLN) and formulate a hydrogel for enhanced topical delivery of aceclofenac (ACF). The SLN were prepared by the ultrasonic emulsification method and optimized on the basis of stirring speed and lipid content. The optimized formulation was characterized for particle size (189 ± 9.2 nm), polydispersity index (PDI) (0.162 ± 0.02), zeta potential (-32.51 ± 0.12 mV), entrapment efficiency (86.51 ± 2.46%), surface morphology, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). In vivo performance of ACF-loaded SLN hydrogel showed prolonged inhibition of edema, as compared to that observed using plain ACF hydrogel, after 24 h. The results demonstrated that the ACF-SLN formulation for skin targeting could be a promising carrier for topical delivery of ACF.

Preparation and characterization of floating drug delivery system of azithromycin.

The objective of present study was to develop a stomach drug delivery system of azithromycin (AZH) as a model drug for eradication of Helicobacter pyloni (H. pylori). Floating microspheres of AZH were prepared by the solvent evaporation method. The prepared microspheres were subjected to evaluation for particle size, incorporation efficiency, in vitro buoyancy and in vitro drug release characteristics. The formulations were prepared at a variable stirring rate (300 to 500 rpm) and temperature (30-50 degrees C). Surface morphology characteristics were studied using scanning electron microscopy (SEM). The mean particle size of the microspheres significantly increased with increasing polymer concentration and was in the range 252.26 +/- 6.50 to 380.91 +/- 4.59 microm. Angle of repose was between 26.42 to 35.83 degrees. Tapped density ranged between 0.493 to 0.612 g/cm3. The compressibility index of all formulations was found to be in the range of 12.41 to 17.16%, which was < 20 indicating good flow characteristics. The encapsulation efficiency of the prepared microspheres was in the range of 27.8 +/- 4.30 to 66.23 +/- 2.08%. The physical state of the drug, before and after formulation was determined by differential scanning calorimetry (DSC). Percentage buoyancy of the microspheres was in the range 45.52 +/- 0.69 to 68.71 +/- 0.61% for 8 h. In vitro drug release studies were performed in simulated gastrointestinal fluid (SGF), pH 2.0 as dissolution medium (900 mL) for 8 h. Effects of stirring rate during preparation, polymer concentration and temperature on the size of microspheres and drug release were also observed. The results of the present studies indicated that the floating microspheres of AZH were formulated to provide site specific delivery of drug with a view to provide an effective and safe therapy for eradication of H. pylori with a reduced dose and reduced duration of therapy.

Hepatoprotective properties of Bauhinia variegata bark extract.

Bauhinia variegata (Leguminosae) commonly known as Kachnar, is widely used in Ayurveda as tonic to the liver. The present work was carried out to assess the potential of Bauhinia variegata bark as hepatoprotective agent. The hepatoprotective activity was investigated in carbon tetrachloride (CCl(4)) intoxicated Sprague-Dawley rats. Bauhinia variegata alcoholic Stem Bark Extract (SBE) at different doses (100 and 200 mg/kg) were administered orally to male Sprague-Dawley rats weighing between 100-120 g. The effect of SBE on the serum marker enzymes, viz., AST, ALT, ALP and GGT and liver protein and lipids were assessed. The extract exhibited significant hepatoprotective activity. Hence, B. variegata appears to be a promising hepatoprotective agent.