scholarly journals Monoolein Assisted Oil-Based Transdermal Delivery of Powder Vaccine

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 814
Author(s):  
Momoko Kitaoka ◽  
Atsushi Oka ◽  
Masahiro Goto
Keyword(s):  
Ex Vivo ◽  
Skin Permeation ◽  
Lipid Extraction ◽  
Skin Penetration ◽  
Isopropyl Myristate ◽  
Transdermal Administration ◽  
Common Skin ◽  
Model Protein ◽  
Specific Igg

An increasing number of protein vaccines have been researched for cancer, inflammation, and allergy therapies. Most of the protein therapeutics are administered through injection because orally-administered proteins are metabolized by the digestive system. Although transdermal administration has received increasing attention, the natural barrier formed by the skin is an obstacle. Monoolein is a common skin penetration enhancer that facilitates topical and transdermal drug delivery. Conventionally, it has been used in an aqueous vehicle, often with polyhydric alcohols. In the current study, monoolein was dissolved in an oil vehicle, isopropyl myristate, to facilitate the skin permeation of powder proteins. The skin permeabilities of the proteins were examined in-vivo and ex-vivo. Monoolein concentration-dependently enhanced the skin permeation of proteins. The protein permeability correlated with the zeta potential of the macromolecules. Dehydration of the stratum corneum (SC), lipid extraction from the SC, and disordering of ceramides caused by monoolein were demonstrated through Fourier transform infrared spectroscopic analysis and small-angle X-ray scattering analysis. An antigen model protein, ovalbumin from egg white, was delivered to immune cells in living mice, and induced antigen-specific IgG antibodies. The patch system showed the potential for transdermal vaccine delivery.

scholarly journals Evaluation of Skin Permeation and Retention of Topical Dapsone in Murine Cutaneous Leishmaniasis Lesions

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 607
Author(s):  
Moreno ◽  
Calvo ◽  
Schwartz ◽  
Navarro-Blasco ◽  
González-Peñas ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Topical Therapy ◽  
Parasite Burden ◽  
Skin Penetration ◽  
High Plasma

The oral administration of dapsone (DAP) for the treatment of cutaneous leishmaniasis (CL) is effective, although serious hematological side effects limit its use. In this study, we evaluated this drug for the topical treatment of CL. As efficacy depends on potency and skin penetration, we first determined its antileishmanial activity (IC50 = 100 μM) and selectivity index in vitro against Leishmania major-infected macrophages. In order to evaluate the skin penetration ex vivo, we compared an O/W cream containing DAP that had been micronized with a pluronic lecithin emulgel, in which the drug was solubilized with diethylene glycol monoethyl ether. For both formulations we obtained similar low flux values that increased when the stratum corneum and the epidermis were removed. In vivo efficacy studies performed on L. major-infected BALB/c mice revealed that treatment not only failed to cure the lesions but made their evolution and appearance worse. High plasma drug levels were detected and were concomitant with anemia and iron accumulation in the spleen. This side effect was correlated with a reduction of parasite burden in this organ. Our results evidenced that DAP in these formulations does not have an adequate safety index for use in the topical therapy of CL.

scholarly journals A NOVEL VESICULAR APPROACH FOR TRANSDERMAL ADMINISTRATION OF ENALAPRIL MALEATE LOADED NANOPRONIOSOMAL GEL: FORMULATION, EX VIVO EVALUATION AND IN VIVO ANTIHYPERTENSIVE STUDY

2020 ◽  
pp. 190-202
Author(s):  
M. SABAREESH ◽  
J. P. YANADAIAH ◽  
K. B. CHANDRA SEKHAR
Keyword(s):  
Ex Vivo ◽  
Skin Permeation ◽  
Skin Irritation ◽  
Physicochemical Characterization ◽  
Size Analysis ◽  
Transdermal Administration ◽  
Enalapril Maleate ◽  
Treatment Of Hypertension ◽  
Permeation Studies

Objective: The objective of the study was to formulate and evaluate the nanoproniosomal gel of Enalapril maleate (EM) for the treatment of hypertension through the transdermal administration and to provide better bioavailability. Methods: The nanoproniosomal gel of the EM was formulated by Lecithin, Cholesterol, Non-ionic surfactants using the Coacervation-phase separation method. The prepared nanoproniosomal gels were evaluated for pH and viscosity, vesicle size analysis, rate of spontaneity, entrapment efficiency, zeta potential, ex vivo skin permeation studies, skin irritation test, stability studies and in vivo antihypertensive studies. Results: Physical characterization was found to be within acceptable limits. The ex vivo skin permeation studies showed the cumulative permeation of 58.75 % to 89.72 % through the albino rat skin in 24 h for all the formulations, which indicate the zero-order drug permeation with diffusion, non-fickian release. Among all formulations, EMNP7 was selected as best formulation because it showed better characteristics than other formulations in several aspects like physicochemical characterization, ex vivo skin permeation studies, permeation kinetics, and other evaluation parameters. The skin irritation study revealed that there was no irritation after topical application and it was found to be safer to use. The In vivo antihypertensive study revealed that the formulation of EMNP7 was successful to regress the rat blood pressure (BP) to normal values in experimental hypertensive rats. Conclusion: The nanoproniosomal gel is an efficient transdermal therapeutic system for the delivery of EM for the treatment of hypertension. It is suitable for once a day controlled release formulation.

A nontoxic ionic liquid composition for the delivery of biological macromolecular anions across the skin barrier

2021 ◽  
Author(s):  
Neeraj Kumar ◽  
Balraj Saini ◽  
Rajwinder Kaur
Keyword(s):  
Ionic Liquids ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Skin Barrier ◽  
Skin Penetration ◽  
Liquid Composition ◽  
Cell Internalization ◽  
Dermal Delivery ◽  
In Vivo Cytotoxicity

The development of biocompatible ionic liquids is needed in order to explore their vastly underutilized pharmaceutical potential. US10912834 patent discloses ionic liquids comprising macromolecular biological anions and alkylated cations, which provides enhanced dermal delivery and cell internalization of the large biological anions. The studies of ex vivo permeation through excised pig skin indicated significantly higher skin penetration of percent dose and enhanced drug internalization was achieved using these ionic liquids. Although, the patent advances an infant field of biological macromolecule-based ionic liquids, the evaluation of these claimed ionic liquids relies only on the in vivo cytotoxicity data and ex vivo skin permeation behavior. Exhaustive studies, including dermatokinetic evaluation and long-term animal toxicity experiments, should be performed in order to unravel the potential of the aforementioned ionic liquids.

scholarly journals Development of Pranoprofen Loaded Nanostructured Lipid Carriers to Improve Its Release and Therapeutic Efficacy in Skin Inflammatory Disorders

Nanomaterials ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 1022 ◽  
Author(s):  
María Rincón ◽  
Ana Calpena ◽  
María-José Fabrega ◽  
María Garduño-Ramírez ◽  
Marta Espina ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Skin Penetration ◽  
Nanostructured Lipid Carriers ◽  
Penetration Enhancers ◽  
Morphological Properties ◽  
Anti Inflammatory ◽  
Dermal Oedema

Pranoprofen (PF)-loaded nanostructured lipid carriers (NLCs), prepared using a high-pressure homogenization method, have been optimized and characterized to improve the biopharmaceutical profile of the drug. The optimized PF-NLCs exhibited physicochemical characteristics and morphological properties that were suitable for dermal application. Stability assays revealed good physical stability, and the release behavior of PF from these NLCs showed a sustained release pattern. Cell viability results revealed no toxicity. Ex vivo human skin permeation studies in Franz diffusion cells were performed to determine the influence of different skin penetration enhancers (pyrrolidone, decanol, octanoic acid, nonane, menthone, squalene, linoleic acid, and cineol) on skin penetration and retention of PF, being the highest dermal retention in the presence of linoleic acid. The selected formulations of NLCs exhibited a high retained amount of PF in the skin and no systemic effects. In vivo mice anti-inflammatory efficacy studies showed a significant reduction in dermal oedema. NLCs containing linoleic acid presented better anti-inflammatory efficacy by decreasing the production of interleukins in keratinocytes and monocytes. The biomechanical properties of skin revealed an occlusive effect and no hydration power. No signs of skin irritancy in vivo were detected. According to these results, dermal PF-NLCs could be an effective system for the delivery and controlled release of PF, improving its dermal retention, with reduced dermal oedema as a possible effect of this drug.

Chemical Permeation Enhancers for Transdermal Delivery of Thiocolchicoside: Assessment of Ex-vivo Skin Flux and In-vivo Pharmacokinetics

2017 ◽  
Vol 10 (5) ◽  
pp. 3827-3835
Author(s):  
Y Madhusudan Rao ◽  
Gayatri P ◽  
Ajitha M ◽  
P. Pavan Kumar ◽  
Kiran kumar
Keyword(s):  
Passive Control ◽  
Ex Vivo ◽  
Skin Permeation ◽  
In Vivo Studies ◽  
Permeation Enhancers ◽  
Casting Technique ◽  
Chemical Permeation Enhancers ◽  
Chemical Permeation ◽  
In Vivo Pharmacokinetics

Present investigation comprises the study of ex-vivo skin flux and in-vivo pharmacokinetics of Thiocolchicoside (THC) from transdermal films. The films were fabricated by solvent casting technique employing combination of hydrophilic and hydrophobic polymers. A flux of 18.08 µg/cm2h and 13.37µg/cm2h was achieved for optimized formulations containing 1, 8-cineole and oleic acid respectively as permeation enhancers. The observed flux values were higher when compared to passive control (8.66 µg/cm2h). Highest skin permeation was observed when 1,8-cineole was used as chemical permeation enhancer and it considerably (2-2.5 fold) improved the THC transport across the rat skin. In vivo studies were performed in rabbits and samples were analysed by LC-MS-MS. The mean area under the curve (AUC) values of transdermal film showed about 2.35 times statistically significant (p<0.05) improvement in bioavailability when compared with the oral administration of THC solution. The developed transdermal therapeutic systems using chemical permeation enhancers were suitable for drugs like THC in effective management of muscular pain.    

scholarly journals Nanostructured Lipid Carrier Gel for the Dermal Application of Lidocaine: Comparison of Skin Penetration Testing Methods

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 310 ◽  
Author(s):  
Stella Zsikó ◽  
Kendra Cutcher ◽  
Anita Kovács ◽  
Mária Budai-Szűcs ◽  
Attila Gácsi ◽  
...  
Keyword(s):  
Drug Release ◽  
Human Skin ◽  
Ex Vivo ◽  
Study Drug ◽  
Skin Penetration ◽  
Human Epidermis ◽  
Nanostructured Lipid Carrier ◽  
Experimental Findings

The aim of this research was to investigate the stability of a lidocaine-loaded nanostructured lipid carrier dispersion at different temperatures, formulate a nanostructured lipid carrier gel, and test the penetration profile of lidocaine from the nanostructured lipid carrier gel using different skin penetration modeling methods. The formulations were characterized by laser diffraction, rheological measurements and microscopic examinations. Various in vitro methods were used to study drug release, diffusion and penetration. Two types of vertical Franz diffusion cells with three different membranes, including cellulose, Strat-M®, and heat separated human epidermis were used and compared to the Skin-parallel artificial membrane permeability assay (PAMPA) method. Results indicated that the nanostructured lipid carrier dispersion had to be gelified as soon as possible for proper stability. Both the Skin-PAMPA model and Strat-M® membranes correlated favorably with heat separated human epidermis in this research, with the Strat-M® membranes sharing the most similar drug permeability profile to an ex vivo human skin model. Our experimental findings suggest that even when the best available in vitro experiment is selected for modeling human skin penetration to study nanostructured lipid carrier gel systems, relevant in vitro/in vivo correlation should be made to calculate the drug release/permeation in vivo. Future investigations in this field are still needed to demonstrate the influence of membranes and equipment from other classes on other drug candidates.

scholarly journals p-Coumaric Acid as An Active Ingredient in Cosmetics: A Review Focusing on its Antimelanogenic Effects

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 275 ◽  
Author(s):  
Yong Chool Boo
Keyword(s):  
Active Ingredient ◽  
Antioxidant Activities ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Skin Pigmentation ◽  
Experimental Models ◽  
Coumaric Acid ◽  
Inflammatory Reactions ◽  
Skin Lightening

Controlling unwanted hyperpigmentation is a major challenge in dermatology and cosmetology, and safe and efficacious antimelanogenic agents are deemed useful for this purpose. p-Coumaric acid is a natural metabolite contained in many edible plants, and its antioxidant activities in reducing oxidative stress and inflammatory reactions have been demonstrated in various experimental models. p-Coumaric acid has the optimal structure to be a competitive inhibitor of tyrosinase that catalyzes key reactions in the melanin biosynthetic pathway. Experimental evidence supports this notion as it was found to be a more potent inhibitor of tyrosinase, especially toward human enzymes, than other well-known tyrosinase inhibitors such as arbutin and kojic acid. p-Coumaric acid inhibited melanin synthesis in murine melanoma cells, human epidermal melanocytes, and reconstituted three-dimensional human skin models. Ex-vivo skin permeation experiments and in-vivo efficacy tests for p-coumaric acid confirmed its efficient transdermal delivery and functional efficacy in reducing erythema development and skin pigmentation due to ultraviolet radiation exposure. Human studies further supported its effectiveness in hypopigmentation and depigmentation. These findings suggest that p-coumaric acid has good potential to be used as a skin-lightening active ingredient in cosmetics. Future studies are needed to extensively examine its safety and efficacy and to develop an optimized cosmetic formulation for the best performance in skin lightening.

scholarly journals Echinacea angustifolia DC. Lipophilic Extract Patch for Skin Application: Preparation, In Vitro and In Vivo Studies

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1096
Author(s):  
Dritan Hasa ◽  
Simon Žakelj ◽  
Iztok Grabnar ◽  
Francesco Cilurzo ◽  
Stefano Dall’Acqua ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Skin Permeation ◽  
In Vivo Studies ◽  
Pharmacokinetic Analysis ◽  
Echinacea Angustifolia ◽  
Transdermal Administration ◽  
Lipophilic Extract ◽  
Main Component

Dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamide (tetraene) is the main component of Echinacea angustifolia DC. lipophilic extract, the bioavailability and immunomodulatory effect after oral administration in soft gel capsules in healthy volunteers of which we have already demonstrated. In the present work, we assessed the transdermal administration as an alternative route of administration of such an alkamide. The first step, therefore, encompassed the preparation of a drug-in-adhesive patch with an area of 868 mm2 and containing a dose of 0.64 mg of tetraene. In vitro skin permeation studies in Franz-type diffusion chambers resulted in a tetraene flux of (103 ± 10) ng × cm−2 × h−1 with a very good linearity (r = 0.99). The relatively low lag time of just 13 min indicates low binding and the accumulation of tetraene in the skin. Finally, the patch was administered to six healthy volunteers, and the pharmacokinetic analysis was performed by nonlinear mixed effects modelling with soft gel oral capsules serving as the reference formulation. The in vivo results correlated well with the in vitro permeation and indicated an initial burst tetraene absorption from the patch that was in parallel with the zero-order kinetics of absorption. The rate of the latter process was in good agreement with the one estimated in vitro. The tetraene absorption rate was therefore slow and prolonged with time, resulting in a bioavailability of 39% relative to the soft gel capsules and a very flat plasma concentration profile.

scholarly journals Nanocrystals of Fusidic Acid for Dual Enhancement of Dermal Delivery and Antibacterial Activity: In Vitro, Ex Vivo and In Vivo Evaluation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 199 ◽  
Author(s):  
Iman S. Ahmed ◽  
Osama S. Elnahas ◽  
Nouran H. Assar ◽  
Amany M. Gad ◽  
Rania El Hosary
Keyword(s):  
Fusidic Acid ◽  
Therapeutic Efficacy ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Fold Increase ◽  
Spherical Particles ◽  
Resistant Bacteria ◽  
Infection Model

With the alarming rise in incidence of antibiotic-resistant bacteria and the scarcity of newly developed antibiotics, it is imperative that we design more effective formulations for already marketed antimicrobial agents. Fusidic acid (FA), one of the most widely used antibiotics in the topical treatment of several skin and eye infections, suffers from poor water-solubility, sub-optimal therapeutic efficacy, and a significant rise in FA-resistant Staphylococcus aureus (FRSA). In this work, the physico-chemical characteristics of FA were modified by nanocrystallization and lyophilization to improve its therapeutic efficacy through the dermal route. FA-nanocrystals (NC) were prepared using a modified nanoprecipitation technique and the influence of several formulation/process variables on the prepared FA-NC characteristics were optimized using full factorial statistical design. The optimized FA-NC formulation was evaluated before and after lyophilization by several in-vitro, ex-vivo, and microbiological tests. Furthermore, the lyophilized FA-NC formulation was incorporated into a cream product and its topical antibacterial efficacy was assessed in vivo using a rat excision wound infection model. Surface morphology of optimized FA-NC showed spherical particles with a mean particle size of 115 nm, span value of 1.6 and zeta potential of −11.6 mV. Differential scanning calorimetry and powder X-ray diffractometry confirmed the crystallinity of FA following nanocrystallization and lyophilization. In-vitro results showed a 10-fold increase in the saturation solubility of FA-NC while ex-vivo skin permeation studies showed a 2-fold increase in FA dermal deposition from FA-NC compared to coarse FA. Microbiological studies revealed a 4-fofd decrease in the MIC against S. aureus and S. epidermidis from FA-NC cream compared to commercial Fucidin cream. In-vivo results showed that FA-NC cream improved FA distribution and enhanced bacterial exposure in the infected wound, resulting in increased therapeutic efficacy when compared to coarse FA marketed as Fucidin cream.

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