The factors determining the skin penetration and cellular uptake of nanocarriers: New hope for clinical development

2021 ◽  
Vol 27 ◽  
Author(s):  
Afsaneh Farjami ◽  
Sara Salatin ◽  
Samira Jafari ◽  
Mohammad Mahmoudian ◽  
Mitra Jelvehgari
Keyword(s):  
Drug Delivery ◽  
Skin Permeation ◽  
Direct Interaction ◽  
Skin Barrier ◽  
Skin Penetration ◽  
Physicochemical Characteristics ◽  
Skin Permeability ◽  
Topical Drug Delivery ◽  
Major Barrier ◽  
Composition And Structure

: The skin provides a protective barrier against toxic environments and also offers a valuable route for topical drug delivery. The stratum corneum (SC) is the outermost layer of the skin and serves as the major barrier to chemical transfer through the skin. The human skin barrier is particularly diffcult to overcome because of the complex composition and structure of the SC. Nanoparticulate carriers have gained widespread attention in topical drug delivery due to their tunable and versatile properties. The present review summarizes the main factors involved in the skin penetration of nanocarriers containing drug. Employment of nanotechnology in topical delivery has grown progressively during recent years; however, it is important to monitor the skin penetration of nanocarriers prior to their use due to avoid possible toxic effects. Nanocarriers can act as a means to increase the skin permeation of drugs by supporting a direct interaction with the SC and increasing the period of permanence on the skin. The skin penetration is influenced by the physicochemical characteristics of nanocarriers such as composition, size, shape, surface chemistry as well as skin features. Considering that the target of topical systems based on nanocarriers is the penetration of therapeutic agents in the skin layers, so a detailed understanding of the factors influencing skin permeability of nanocarriers is essential for safe and efficient therapeutic applications.

Limitations and Opportunities in Topical Drug Delivery: Interaction Between Silica Nanoparticles and Skin Barrier

2019 ◽  
Vol 25 (4) ◽  
pp. 455-466 ◽  
Author(s):  
Francisco Arriagada ◽  
Javier Morales
Keyword(s):  
Drug Delivery ◽  
Adverse Effects ◽  
Silica Nanoparticles ◽  
Skin Barrier ◽  
Skin Penetration ◽  
Bioactive Compound ◽  
Penetration Enhancers ◽  
Topical Drug Delivery ◽  
Skin Delivery ◽  
The Stability

The first limiting barrier for the transport in the skin is the stratum corneum; different strategies have been developed to overcome this barrier, including chemical enhancers. However, these penetration enhancers have limitations, including toxic adverse effects. In this context, research into nanomaterials has provided new tools to increase the residence time of drugs by generating a reservoir, increasing the specificity of drugs and reducing their adverse effects, and improving the penetration of drugs that are difficult to formulate. Silica nanoparticles have been proposed as suitable nanocarriers for skin delivery. Unfortunately, the mechanisms involved in the interaction, transport and fate of silica nanoparticles in the skin have not been fully investigated. This paper reviews significant findings about the interaction between silica-based nanocarriers and the skin. First, this review focuses on the properties and functions of the skin, the skin penetration properties of silica nanoparticles, their synthesis strategies and their toxicity. Finally, advances and evidence on the application of silica nanocarriers in skin drug delivery are provided, in which the use of nanoparticles increases the stability and solubility of the bioactive compound, enhancing its performance, act as penetrator enhancer and improving controlled release. Thus, improving the treatment of some skin disorders.

Topical Drug Delivery of Anti-infectives Employing Lipid-Based Nanocarriers: Dermatokinetics as an Important Tool

2019 ◽  
Vol 24 (43) ◽  
pp. 5108-5128 ◽  
Author(s):  
Kanika Thakur ◽  
Gajanand Sharma ◽  
Bhupindar Singh ◽  
Om Prakash Katare
Keyword(s):  
Drug Delivery ◽  
Infectious Diseases ◽  
Patient Compliance ◽  
Skin Permeation ◽  
Skin Penetration ◽  
Topical Delivery ◽  
Controlled Drug Release ◽  
Topical Drug Delivery ◽  
Promising Strategy ◽  
Drug Resistant Strains

Background:The therapeutic approaches for the management of topical infections have always been a difficult approach due to lack of efficacy of conventional topical formulations, high frequency of topical applications and non-patient compliance. The major challenge in the management of topical infections lies in antibiotic resistance which leads to severe complications and hospitalizations resulting in economic burden and high mortality rates.Methods:Topical delivery employing lipid-based carriers has been a promising strategy to overcome the challenges of poor skin permeation and retention along with large doses which need to be administered systemically. The use of lipid-based delivery systems is a promising strategy for the effective topical delivery of antibiotics and overcoming drug-resistant strains in the skin. The major systems include transfersomes, niosomes, ethosomes, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion and nanoemulsion as the most promising drug delivery approaches to treat infectious disorders. The main advantages of these systems include lipid bilayer structure which mimics the cell membrane and can fuse with infectious microbes. The numerous advantages associated with nanocarriers like enhanced efficacy, improvement in bioavailability, controlled drug release and ability to target the desired infectious pathogen have made these carriers successful.Conclusion:Despite the number of strides taken in the field of topical drug delivery in infectious diseases, it still requires extensive research efforts to have a better perspective of the factors that influence drug permeation along with the mechanism of action with regard to skin penetration and deposition. The final objective of the therapy is to provide a safe and effective therapeutic approach for the management of infectious diseases affecting topical sites leading to enhanced therapeutic efficacy and patient-compliance.

scholarly journals Lanolin-Based Synthetic Membranes for Transdermal Permeation and Penetration Drug Delivery Assays

Membranes ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 444
Author(s):  
Cristina Alonso ◽  
Ilaria Collini ◽  
Meritxell Martí ◽  
Clara Barba ◽  
Luisa Coderch
Keyword(s):  
Ph Value ◽  
Skin Permeation ◽  
Diclofenac Sodium ◽  
Skin Penetration ◽  
Skin Surface ◽  
Skin Permeability ◽  
Active Compounds ◽  
Synthetic Membranes ◽  
Composition And Structure ◽  
Permeability Studies

Due to the high similarity in composition and structure between lanolin and human SC lipids, we will work with two models from wool wax. Two types of lanolin were evaluated: one extracted with water and surfactants (WEL) and the other extracted with organic solvents (SEL). Skin permeation and skin penetration studies were performed with two active compounds to study the feasibility of the use of lanolin-based synthetic membranes as models of mammalian skin. Diclofenac sodium and lidocaine were selected as the active compounds considering that they have different chemical natures and different lipophilicities. In the permeation assay with SEL, a better correlation was obtained with the less permeable compound diclofenac sodium. This assay suggests the feasibility of using artificial membranes with SEL as a model for percutaneous absorption studies, even though the lipophilic barrier should be improved. Penetration profiles of the APIs through the SEL and WEL membranes indicated that the two membranes diminish penetration and can be considered good membrane surrogates for skin permeability studies. However, the WEL membranes, with a pH value similar to that of the skin surface, promoted a higher degree of diminution of the permeability of the two drugs, similar to those found for the skin.

scholarly journals Topical Artocarpus communis Nanoparticles Improved the Water Solubility and Skin Permeation of Raw A. communis Extract, Improving Its Photoprotective Effect

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1372
Author(s):  
Chun-Yin Yang ◽  
Pao-Hsien Huang ◽  
Chih-Hua Tseng ◽  
Feng-Lin Yen
Keyword(s):  
Water Solubility ◽  
Methanol Extract ◽  
Biological Effects ◽  
Skin Permeation ◽  
Environmental Pollutants ◽  
Skin Penetration ◽  
Physicochemical Characteristics ◽  
The Poor ◽  
Deep Layers ◽  
Poor Water Solubility

Antioxidants from plant extracts are often used as additives in skincare products to prevent skin problems induced by environmental pollutants. Artocarpus communis methanol extract (ACM) has many biological effects, such as antioxidant, anti-inflammatory, wound healing, and photoprotective effects; however, the poor water solubility of raw ACM has limited its applications in medicine and cosmetics. Topical antioxidant nanoparticles are one of the drug-delivery systems for overcoming the poor water solubility of antioxidants for increasing their skin penetration. The present study demonstrated that ACM-loaded hydroxypropyl-β-cyclodextrin and polyvinylpyrrolidone K30 nanoparticles (AHP) were successfully prepared and could effectively increase the skin penetration of ACM through changing the physicochemical characteristics of raw ACM, including reducing the particle size, increasing the surface area, and inducing amorphous transformation. Our results also revealed that AHP had significantly better antioxidant activity than raw ACM for preventing photocytotoxicity because the AHP formulation increased the cellular uptake of the ACM in UVB-irradiated HaCaT keratinocytes. In conclusion, our results suggest that AHP may be used as a good topical antioxidant nanoparticle for delivering ACM into deep layers of the skin for preventing UVB-induced skin problems.

scholarly journals FORMULATION AND IN VITRO CHARACTERISATION OF SOYBEAN OIL-HPMCK4M BASED BIGEL MATRIX FOR TOPICAL DRUG DELIVERY

2019 ◽  
pp. 33-38
Author(s):  
SHUBHAM MUKHERJEE ◽  
SUTAPA BISWAS MAJEE ◽  
GOPA ROY BISWAS
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Soybean Oil ◽  
Skin Permeation ◽  
Topical Drug Delivery ◽  
Zero Order Kinetics ◽  
Wide Range ◽  
Span 60 ◽  
Hydrophilic Gel

Objective: Hydrogels with scope for utilization in numerous fields possess limited applications due to problems in incorporating wide range of drugs and crossing the lipophilic barrier of the skin. Attempts to overcome these problems by developing organogel hold drawbacks. Challenges posed by drug lipophilicity or skin permeation can be solved by developing bigel formed via combination of lipophilic and hydrophilic gel phases in a definite proportion. The objective of the present study is to formulate and characterize matrix type bigel of soybean oil and HPMCK4M for topical drug delivery. Methods: Four batches of bigels were developed with two organogel formulations of soybean oil containing 20 and 22% w/v Span 60. Both organogels and bigels were examined for compatibility by FTIR spectroscopy, hemocompatibility and characterized for physical appearance, pH, rheological behavior and in vitro drug release pattern. Results: FTIR study confirmed compatibility between paracetamol and components of organogel or bigel. The oily feel of organogels disappeared with bigels which possessed a creamy and smooth texture. Pseudoplastic behaviour was confirmed by Ostwald-de wale power-law model in both organogels and bigels. Improved drug release was observed in bigel (BG1) formulation containing 3%w/v HPMCK4M and soybean oil based organogel with 20% w/v Span 60 as compared to the corresponding organogel (OG1). Organogels were foundto follow either zero-order kinetics (OG1) or Korsmeyer-Peppasmodel (OG2) while the formation of matrix was exhibited in bigels with drug diffusion predominantly of non-Fickian type. Conclusion: Therefore, bigels of soybean oil based organogel with HPMCK4M hydrogel formed gel matrix demonstrating improved drug release for topical application compared to organogel.

scholarly journals Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels

Pharmaceutics ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 394 ◽  
Author(s):  
Fiorenza Rancan ◽  
Hildburg Volkmann ◽  
Michael Giulbudagian ◽  
Fabian Schumacher ◽  
Jessica Isolde Stanko ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Skin Barrier ◽  
Skin Penetration ◽  
Jurkat Cells ◽  
Skin Permeability ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hydration Properties ◽  
Tacrolimus Ointment ◽  
Proliferative Effect ◽  
Inflammatory Conditions

Polyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrolimus ointment. The penetration of the drug was investigated in ex vivo abdominal and breast skin, while different methods for skin barrier disruption were investigated to improve skin permeability or simulate inflammatory conditions with compromised skin barrier. The amount of penetrated tacrolimus was measured in skin extracts by liquid chromatography tandem-mass spectrometry (LC-MS/MS), whereas the inflammatory markers IL-6 and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). Higher amounts of tacrolimus penetrated in breast as compared to abdominal skin or in barrier-disrupted as compared to intact skin, confirming that the stratum corneum is the main barrier for tacrolimus skin penetration. The anti-proliferative effect of the penetrated drug was measured in skin tissue/Jurkat cells co-cultures. Interestingly, tNGs exhibited similar anti-proliferative effects as the 0.1% tacrolimus ointment. We conclude that polyglycerol-based nanogels represent an interesting alternative to paraffin-based formulations for the treatment of inflammatory skin conditions.

scholarly journals Microneedle Array Patches: Characterization and in -vitro Evaluation

2021 ◽  
Vol 30 (1) ◽  
pp. 66-75
Author(s):  
Zainab A. Sadeq
Keyword(s):  
Drug Delivery ◽  
Blood Vessel ◽  
Transdermal Drug Delivery ◽  
Skin Barrier ◽  
Skin Penetration ◽  
Solid Polymer ◽  
Microneedle Array ◽  
Microneedle Patch ◽  
Novel Drug

 Patch in transdermal drug delivery(TDDS) used to overcome the hypodermic drawback, but these patch also have absorption limitation for hydrophilic and macromolecule like peptide and DNA. So that micronized projection have the ability for skin penetration developed named as microneedle.  Microneedle drug delivery system is a novel drug delivery to overcome the limitation of TDDS like skin barrier restriction for large molecule. Microneedle patch can penetrate through skin subcutaneous into epidermis, avoiding nerve fiber and blood vessel contact. There are many type of microneedle patch like solid, polymer, hallow, hydrogel forming microneedle and dissolving microneedle with different method of microfabrication

Ionic liquids with N-methyl-2-pyrrolidonium cation as an enhancer for topical drug delivery: Synthesis, characterization, and skin-penetration evaluation

2020 ◽  
Vol 299 ◽  
pp. 112166 ◽  
Author(s):  
Rahman Md Moshikur ◽  
Md Raihan Chowdhury ◽  
Rie Wakabayashi ◽  
Yoshiro Tahara ◽  
Noriho Kamiya ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Ionic Liquids ◽  
Skin Penetration ◽  
Topical Drug Delivery

Development and Evaluation of Ketoconazole Loaded Nano-sponges for Topical Drug Delivery

2018 ◽  
Vol 11 (4) ◽  
pp. 4154-4162
Author(s):  
Harshal A. Pardeshi ◽  
Makarand S Gambhire ◽  
Kishore N. Gujar ◽  
Aniket A Vaidhya
Keyword(s):  
Drug Delivery ◽  
Antifungal Activity ◽  
Drug Release ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Controlled Drug Release ◽  
Topical Drug Delivery ◽  
Molar Ratios ◽  
Skin Targeting ◽  
Skin Retention

Beta-cyclodextrin nanosponges (NS) based hydrogel had been studied as a topical delivery of ketoconazole (KTZ) for effective eradication of cutaneous fungal infection. The purpose of the present study was to develop KTZ loaded NS for topical drug delivery with skin targeting to minimizing the adverse side effects and providing a controlled release. The four types of NS were synthesized by varying the molar ratios of β-cyclodextrin (β-CD) to diphenylcarbonate (DPC) as a cross linker viz. 1:2, 1:4, 1:6, and 1:8. The KTZ loaded NS shows particle size 274.6-367 nm and high loading efficacy was obtained, FTIR, DSC, XRD studies confirmed the complexation of KTZ with NS. Hydrogel were evaluated comparatively with commercial product with respect to physicochemical properties, ex-vivo skin permeation and skin retention on human cadaver skin and antifungal activity. Ex-vivo study of KTZ-NS hydrogel exhibited controlled drug release up to 8 hrs whereas skin retention studies show avoidance of the systemic uptake and better accumulative uptake of the drug compared to marketed formulation. The zone of inhibition of KTZ-NS hydrogel was higher in comparison with commercial formulation against Candida albicans. These results indicate that the KTZ-NS is having controlled drug release, potential of skin targeting with enhanced antifungal activity.

Transfersomes as alternative topical nanodosage forms for the treatment of skin disorders

Nanomedicine ◽  
2021 ◽  
Author(s):  
Pablo Oyarzún ◽  
Eduardo Gallardo-Toledo ◽  
Javier Morales ◽  
Francisco Arriagada
Keyword(s):  
Drug Delivery ◽  
Topical Treatment ◽  
Skin Penetration ◽  
Unique Characteristic ◽  
Topical Drug Delivery ◽  
Skin Disorders ◽  
Therapeutic Applications ◽  
Clinical Benefits ◽  
Pass Through

Topical drug delivery is a promising approach to treat different skin disorders. However, it remains a challenge mainly due to the nature and rigidity of the nanosystems, which limit deep skin penetration, and the unsuccessful demonstration of clinical benefits; greater penetration by itself, does not ensure pharmacological success. In this context, transfersomes have appeared as promising nanosystems; deformability, their unique characteristic, allows them to pass through the epidermal microenvironment, improving the skin drug delivery. This review focuses on the comparison of transfersomes with other nanosystems (e.g., liposomes), discusses recent therapeutic applications for the topical treatment of different skin disorders and highlights the need for further studies to demonstrate significant clinical benefits of transfersomes compared with conventional therapies.

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