Development of Novel Formulations to Enhance in Vivo Transdermal Permeation of Tocopherol

Tocopherol represents a big challenge for transdermal permeation owing to its extreme hydrophobicity and large molecular mass. The aim of the present study was to develop alpha-tocopherol (T) topical formulations and evaluate their ex vivo and in vivo permeation. Franz diffusion cells were used for ex vivo permeation, and neonatal rats were used for in vivo permeation. Seven gel formulations and 21 liquid formulations were investigated for physical stability, viscosity and permeation of T. Analysis of T was performed by a validated HPLC method using a UV detector. The ex vivo permeation from gel and emulsion formulations was very poor (0.001-0.015 %). Highest permeation was observed from monophasic liquid formulations containing dimethyl sulfoxide (DMSO), tocopheryl polyethylene glycols (TPGs), propylene glycol, ethanol and 9.5 % T. The in vivo results demonstrated higher retention in the epidermis compared to subcutaneous tissues, 1377 and 1.13 μg g-1, respectively. Increasing T concentration from 4.8 to 9.5 % did not increase the amount permeated or % of T retained. It was concluded that simple solutions of T in the presence of DMSO and TPGs were more promising systems for effective transdermal permeation compared to gel, emulsion or oleaginous systems.

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Development, Pre-clinical Investigation and Histopathological Evaluation of Metronidazole Loaded Topical Formulation for Treatment of Skin Inflammatory disorders

Drug Delivery Letters ◽

10.2174/2210303110999200821123047 ◽

2020 ◽

Vol 10 ◽

Author(s):

Divya Thakur ◽

Gurpreet Kaur ◽

Sheetu Wadhwa ◽

Ashana Puri

Keyword(s):

Ex Vivo ◽

Clinical Investigation ◽

In Vivo Studies ◽

Tween 20 ◽

Inflammatory Disorders ◽

Rat Paw Edema ◽

Ex Vivo Permeation ◽

Permeation Studies ◽

Anti Inflammatory

Background: Metronidazole (MTZ) is an anti-oxidant and anti-inflammatory agent with beneficial therapeutic properties. The hydrophilic nature of molecule limits its penetration across the skin. Existing commercial formulations have limitations of inadequate drug concentration present at target site, which requires frequent administration and poor patient compliance. Objective: The aim of current study was to develop and evaluate water in oil microemulsion of Metronidazole with higher skin retention for treatment of inflammatory skin disorders. Methods: Pseudo ternary phase diagrams were used in order to select the appropriate ratio of surfactant and co-surfactant and identify the microemulsion area. The selected formulation consisted of Capmul MCM as oil, Tween 20 and Span 20 as surfactant and co-surfactant, respectively, and water. The formulation was characterized and evaluated for stability, Ex vivo permeation studies and in vivo anti-inflammatory effect (carrageenan induced rat paw edema, air pouch model), anti-psoriatic activity (mouse-tail test). Results: The particle size analyses revealed average diameter and polydispersity index of selected formulation to be 16 nm and 0.373, respectively. The results of ex vivo permeation studies showed statistically higher mean cumulative amount of MTZ retained in rat skin from microemulsion i.e. 21.90 ± 1.92 μg/cm2 which was 6.65 times higher as compared to Marketed gel (Metrogyl gel®) with 3.29 ± 0.11 μg/cm2 (p<0.05). The results of in vivo studies suggested the microemulsion based formulation of MTZ to be similar in efficacy to Metrogyl gel®. Conclusion: Research suggests efficacy of the developed MTZ loaded microemulsion in treatment of chronic skin inflammatory disorders.

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Formulation and optimization of terbinafine HCl loaded chitosan/xanthan gum nanoparticles containing gel: Ex-vivo permeation and in-vivo antifungal studies

Journal of Drug Delivery Science and Technology ◽

10.1016/j.jddst.2021.102935 ◽

2021 ◽

pp. 102935

Author(s):

Fahad Pervaiz ◽

Rabia Mushtaq ◽

Sobia Noreen

Keyword(s):

Xanthan Gum ◽

Ex Vivo ◽

Ex Vivo Permeation ◽

Terbinafine Hcl

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Ex-Vivo and In-Vivo Assessment of Cyclamen europaeum Extract After Nasal Administration

Pharmaceutics ◽

10.3390/pharmaceutics11090426 ◽

2019 ◽

Vol 11 (9) ◽

pp. 426

Author(s):

Fernández-Campos ◽

Clares ◽

Rodríguez-Lagunas ◽

Jauregui ◽

Casals ◽

...

Keyword(s):

Ex Vivo ◽

Secretory Activity ◽

Nasal Administration ◽

Diffusion Cells ◽

Freeze Dried ◽

Related Quality ◽

Health Related ◽

Botanical Extract ◽

Franz Diffusion Cells

Rhinosinusitis is a prevalent disorder with a severe impact on the health-related quality of life. Saponins of Cyclamen europaeum exert a clinically proven curative effect on rhinosinusitis symptoms when instilled into the nasal cavity, however, more extensive preclinical assessment is required to better characterize the efficacy of this botanical extract. This work evaluates the potential use of a natural freeze-dried extract of C. europaeum given as topical nasal administration. Permeation experiment on porcine nasal mucosa was performed with Franz diffusion cells. Experiments in rabbits were performed to test for any toxicological, hematological, biochemical or histological evidence of systemic action. No theoretical levels of saponins were found in the receptor chamber of Franz diffusion cells. Hematological data did not show significant differences between control and experimental animals (p > 0.05). Histological studies also showed that enhanced secretory activity in response to intranasal administration was not accompanied by any visible signs of injury. An examination of the brain, lungs, liver, kidneys, spleen, and gastrointestinal organs did not reveal any abnormality. The absence of mucosal permeation of saponins and negligible probability of C. europaeum saponins absorption in the course of a therapeutic application was demonstrated.

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Alpha-tocopherol, an effective inhibitor of platelet adhesion

Blood ◽

10.1182/blood.v73.1.141.141 ◽

1989 ◽

Vol 73 (1) ◽

pp. 141-149 ◽

Cited By ~ 65

Author(s):

J Jandak ◽

M Steiner ◽

PD Richardson

Keyword(s):

Vitamin E ◽

Platelet Adhesion ◽

Ex Vivo ◽

Platelet Rich Plasma ◽

Flow Chamber ◽

Alpha Tocopherol ◽

Tocopherol Concentration ◽

Average Decrease ◽

Platelet Adherence

Abstract Platelet adhesiveness was tested ex vivo in a group of six normal individuals receiving varying doses of alpha-tocopherol. Adhesion to glass slides coated with fibronectin, collagen, fibrinogen, or plasma proteins was studied by perfusing platelet-rich plasma through a flow chamber that allowed time- and space-resolved observations of platelet adhesion. Platelet adherence was measured in an area of parallel flow lines and low shear rate under standardized conditions before and after dietary supplementation with vitamin E at doses of 200 and 400 IU/d. Platelet adherence differed in magnitude depending on the adhesive surface. There was a distinct preference of platelets to adhere to sites that had been previously occupied. A remarkable decrease in platelet adherence was observed after vitamin E supplementation. The average decrease in adhesion after 2 weeks of 200 IU vitamin E was 75%. After 2 weeks of 400 IU vitamin E, platelet adhesion was reduced by 82%. The inhibitory activity of alpha-tocopherol was dose dependent and correlated well with the increase in alpha-tocopherol concentration in platelets after supplementation. Scanning electron microscopy revealed a striking decrease of pseudopodium formation in alpha-tocopherol- enriched platelets. Our results suggest that vitamin E may also be an effective antiadhesive agent in vivo.

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In vivo distribution and ex vivo permeation of cyclosporine A prodrug aqueous formulations for ocular application

Journal of Controlled Release ◽

10.1016/j.jconrel.2013.04.019 ◽

2013 ◽

Vol 170 (1) ◽

pp. 153-159 ◽

Cited By ~ 14

Author(s):

Marta Rodriguez-Aller ◽

Davy Guillarme ◽

Mohamed El Sanharawi ◽

Francine Behar-Cohen ◽

Jean-Luc Veuthey ◽

...

Keyword(s):

Cyclosporine A ◽

Ex Vivo ◽

In Vivo Distribution ◽

Ex Vivo Permeation

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Alpha-tocopherol, an effective inhibitor of platelet adhesion

Blood ◽

10.1182/blood.v73.1.141.bloodjournal731141 ◽

1989 ◽

Vol 73 (1) ◽

pp. 141-149

Author(s):

J Jandak ◽

M Steiner ◽

PD Richardson

Keyword(s):

Vitamin E ◽

Platelet Adhesion ◽

Ex Vivo ◽

Platelet Rich Plasma ◽

Flow Chamber ◽

Alpha Tocopherol ◽

Tocopherol Concentration ◽

Average Decrease ◽

Platelet Adherence

Platelet adhesiveness was tested ex vivo in a group of six normal individuals receiving varying doses of alpha-tocopherol. Adhesion to glass slides coated with fibronectin, collagen, fibrinogen, or plasma proteins was studied by perfusing platelet-rich plasma through a flow chamber that allowed time- and space-resolved observations of platelet adhesion. Platelet adherence was measured in an area of parallel flow lines and low shear rate under standardized conditions before and after dietary supplementation with vitamin E at doses of 200 and 400 IU/d. Platelet adherence differed in magnitude depending on the adhesive surface. There was a distinct preference of platelets to adhere to sites that had been previously occupied. A remarkable decrease in platelet adherence was observed after vitamin E supplementation. The average decrease in adhesion after 2 weeks of 200 IU vitamin E was 75%. After 2 weeks of 400 IU vitamin E, platelet adhesion was reduced by 82%. The inhibitory activity of alpha-tocopherol was dose dependent and correlated well with the increase in alpha-tocopherol concentration in platelets after supplementation. Scanning electron microscopy revealed a striking decrease of pseudopodium formation in alpha-tocopherol- enriched platelets. Our results suggest that vitamin E may also be an effective antiadhesive agent in vivo.

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Nobiletin-loaded composite penetration enhancer vesicles restore the normal miRNA expression and the chief defence antioxidant levels in skin cancer

Scientific Reports ◽

10.1038/s41598-021-99756-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mahitab Bayoumi ◽

Mona G. Arafa ◽

Maha Nasr ◽

Omaima A. Sammour

Keyword(s):

Particle Size ◽

Skin Cancer ◽

Zeta Potential ◽

Ex Vivo ◽

Physical Stability ◽

Entrapment Efficiency ◽

Penetration Enhancer ◽

Oxidative Stress Biomarkers ◽

Skin Deposition

AbstractSkin cancer is one of the most dangerous diseases, leading to massive losses and high death rates worldwide. Topical delivery of nutraceuticals is considered a suitable approach for efficient and safe treatment of skin cancer. Nobiletin; a flavone occurring in citrus fruits has been reported to inhibit proliferation of carcinogenesis since 1990s, is a promising candidate in this regard. Nobiletin was loaded in various vesicular systems to improve its cytotoxicity against skin cancer. Vesicles were prepared using the thin film hydration method, and characterized for particle size, zeta potential, entrapment efficiency, TEM, ex-vivo skin deposition and physical stability. Nobiletin-loaded composite penetration enhancer vesicles (PEVs) and composite transfersomes exhibited particle size 126.70 ± 11.80 nm, 110.10 ± 0.90 nm, zeta potential + 6.10 ± 0.40 mV, + 9.80 ± 2.60 mV, entrapment efficiency 93.50% ± 3.60, 95.60% ± 1.50 and total skin deposition 95.30% ± 3.40, 100.00% ± 2.80, respectively. These formulations were selected for cytotoxicity study on epidermoid carcinoma cell line (A431). Nobiletin-loaded composite PEVs displayed the lowest IC50 value, thus was selected for the in vivo study, where it restored skin condition in DMBA induced skin carcinogenesis mice, as delineated by histological and immuno-histochemical analysis, biochemical assessment of skin oxidative stress biomarkers, in addition to miRNA21 and miRNA29A. The outcomes confirmed that nobiletin- loaded composite PEVs is an efficient delivery system combating skin cancer.

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Ex Vivo Permeation of Carprofen Vehiculated by PLGA Nanoparticles through Porcine Mucous Membranes and Ophthalmic Tissues

Nanomaterials ◽

10.3390/nano10020355 ◽

2020 ◽

Vol 10 (2) ◽

pp. 355 ◽

Cited By ~ 1

Author(s):

Lídia Gómez-Segura ◽

Alexander Parra ◽

Ana Cristina Calpena-Campmany ◽

Álvaro Gimeno ◽

Immaculada Gómez de Aranda ◽

...

Keyword(s):

Ex Vivo ◽

Cell Structure ◽

Topical Administration ◽

Plga Nanoparticles ◽

In Vivo Studies ◽

Ex Vivo Permeation ◽

Mucous Membranes ◽

Anti Inflammatory ◽

Almost All

(1) Background: Carprofen (CP), 2-(6-chlorocarbazole) propionic acid, is used as an anti-inflammatory, analgesic and anti-pyretic agent and it belongs to the family of non-steroidal anti-inflammatory drugs (NSAIDs). CP has some adverse reactions in systemic administration; for this reason, topical administration with CP nanoparticles (CP-NPs) can be an optimal alternative. The main objective of this work is the investigation of ex vivo permeation of CP through different types of porcine mucous membranes (buccal, sublingual and vaginal) and ophthalmic tissues (cornea, sclera and conjunctiva) to compare the influence of CP-NPs formulation over a CP solution (CP-Solution). (2) Methods: The ex vivo permeation profiles were evaluated using Franz diffusion cells. Furthermore, in vivo studies were performed to verify that the formulations did not affect the cell structure and to establish the amount retained (Qr) in the tissues. (3) Results: Permeation of CP-NPs is more effective in terms of drug retention in almost all tissues (with the exception of sclera and sublingual). In vivo studies show that neither of the two formulations affects tissue structure, so both formulations are safe. (4) Conclusions: It was concluded that CP-NPs may be a useful tool for the topical treatment of local inflammation in veterinary and human medicine.

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