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Journal ArticleDOI

Transdermal drug delivery: penetration enhancement techniques.

01 Jan 2005-Current Drug Delivery (Curr Drug Deliv)-Vol. 2, Iss: 1, pp 23-33
TL;DR: Skin penetration enhancement techniques based on drug/vehicle optimisation such as drug selection, prodrugs and ion-pairs, supersaturated drug solutions, eutectic systems, complexation, liposomes, vesicles and particles are described.
Abstract: There is considerable interest in the skin as a site of drug application both for local and systemic effect. However, the skin, in particular the stratum corneum, poses a formidable barrier to drug penetration thereby limiting topical and transdermal bioavailability. Skin penetration enhancement techniques have been developed to improve bioavailability and increase the range of drugs for which topical and transdermal delivery is a viable option. This review describes enhancement techniques based on drug/vehicle optimisation such as drug selection, prodrugs and ion-pairs, supersaturated drug solutions, eutectic systems, complexation, liposomes, vesicles and particles. Enhancement via modification of the stratum corneum by hydration, chemical enhancers acting on the structure of the stratum corneum lipids and keratin, partitioning and solubility effects are also discussed. The mechanism of action of penetration enhancers and retarders and their potential for clinical application is described.
Citations
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Journal ArticleDOI
TL;DR: This review highlights the significance of size and PDI in the successful design, formulation and development of nanosystems for pharmaceutical, nutraceutical and other applications.
Abstract: Lipid-based drug delivery systems, or lipidic carriers, are being extensively employed to enhance the bioavailability of poorly-soluble drugs. They have the ability to incorporate both lipophilic and hydrophilic molecules and protecting them against degradation in vitro and in vivo. There is a number of physical attributes of lipid-based nanocarriers that determine their safety, stability, efficacy, as well as their in vitro and in vivo behaviour. These include average particle size/diameter and the polydispersity index (PDI), which is an indication of their quality with respect to the size distribution. The suitability of nanocarrier formulations for a particular route of drug administration depends on their average diameter, PDI and size stability, among other parameters. Controlling and validating these parameters are of key importance for the effective clinical applications of nanocarrier formulations. This review highlights the significance of size and PDI in the successful design, formulation and development of nanosystems for pharmaceutical, nutraceutical and other applications. Liposomes, nanoliposomes, vesicular phospholipid gels, solid lipid nanoparticles, transfersomes and tocosomes are presented as frequently-used lipidic drug carriers. The advantages and limitations of a range of available analytical techniques used to characterize lipidic nanocarrier formulations are also covered.

1,891 citations


Cites background from "Transdermal drug delivery: penetrat..."

  • ...There are specialized lipid-based encapsulation systems for topical and transdermal drug delivery based on skin penetration enhancement mechanisms and/or certain molecules referred to as “edge activators” [61,62]....

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Journal ArticleDOI
TL;DR: Overall, the current weight of evidence suggests that nano-materials such as nano-sized vesicles or TiO2 and ZnO nanoparticles currently used in cosmetic preparations or sunscreens pose no risk to human skin or human health, although other NP may have properties that warrant safety evaluation on a case-by-case basis before human use.
Abstract: Many modern cosmetic or sunscreen products contain nano-sized components. Nanoemulsions are transparent and have unique tactile and texture properties; nanocapsule, nanosome, noisome, or liposome formulations contain small vesicles (range: 50 to 5000 nm) consisting of traditional cosmetic materials that protect light- or oxygen-sensitive cosmetic ingredients. Transdermal delivery and cosmetic research suggests that vesicle materials may penetrate the stratum corneum (SC) of the human skin, but not into living skin. Depending on the physical/chemical properties of the ingredient and the formulation, nano-sized formulations may enhance or reduce skin penetration, albeit at a limited rate. Modern sunscreens contain insoluble titanium dioxide (TiO2) or zinc oxide (ZnO) nanoparticles (NP), which are colorless and reflect/scatter ultraviolet (UV) more efficiently than larger particles. Most available theoretical and experimental evidence suggests that insoluble NP do not penetrate into or through normal as well as compromised human skin. Oral and topical toxicity data suggest that TiO2 and ZnO NP have low systemic toxicity and are well tolerated on the skin. In vitro cytotoxicity, genotoxicity, and photogenotoxicity studies on TiO2 or other insoluble NP reporting uptake by cells, oxidative cell damage, or genotoxicity should be interpreted with caution, since such toxicities may be secondary to phagocytosis of mammalian cells exposed to high concentrations of insoluble particles. Caution needs to be exercised concerning topical exposure to other NP that either have characteristics enabling some skin penetration and/or have inherently toxic constituents. Studies on wear debris particles from surgical implants and other toxicity studies on insoluble particles support the traditional toxicology view that the hazard of small particles is mainly defined by the intrinsic toxicity of particles, as distinct from their particle size. There is little evidence supporting the principle that smaller particles have greater effects on the skin or other tissues or produce novel toxicities relative to micro-sized materials. Overall, the current weight of evidence suggests that nano-materials such as nano-sized vesicles or TiO2 and ZnO nanoparticles currently used in cosmetic preparations or sunscreens pose no risk to human skin or human health, although other NP may have properties that warrant safety evaluation on a case-by-case basis before human use.

625 citations


Cites background or methods from "Transdermal drug delivery: penetrat..."

  • ...…(Santos et al., 2002), the enhancement has been recognized to be mainly related to an increase in skin hydration produced by an occlusive lipid film formed on the surface of the skin, and not by actual skin penetration of the SLNP themselves (Wissing and Müller, 2003; reviewed by Benson, 2005)....

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  • ...Skin penetration enhancement techniques used in TDD were recently reviewed (Benson, 2005)....

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  • ...…abrasion, skin erosion (suction blisters), electrical (ionophoretic) and mechanical (skin stretching) methods, or other energy-related techniques, such as ultrasound or needleless injection, or by the combination of active and/or passive delivery methods (Benson, 2005; Thomas and Finnin, 2004)....

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  • ...Drug substances marketed today in passive TDD systems all fit into these limits, they have molecular weights between 160 and 360 and a molecular size between 0.75 to 1.6 nm (Benson, 2005; Table 3)....

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Journal ArticleDOI
TL;DR: This paper reviews the latest reports on the potential therapy of skin disorders through treatment with phenolic compounds, considering mostly a single specific compound or a combination of compounds in a plant extract.
Abstract: Phenolic compounds constitute a group of secondary metabolites which have important functions in plants. Besides the beneficial effects on the plant host, phenolic metabolites (polyphenols) exhibit a series of biological properties that influence the human in a health-promoting manner. Evidence suggests that people can benefit from plant phenolics obtained either by the diet or through skin application, because they can alleviate symptoms and inhibit the development of various skin disorders. Due to their natural origin and low toxicity, phenolic compounds are a promising tool in eliminating the causes and effects of skin aging, skin diseases, and skin damage, including wounds and burns. Polyphenols also act protectively and help prevent or attenuate the progression of certain skin disorders, both embarrassing minor problems (e.g., wrinkles, acne) or serious, potentially life-threatening diseases such as cancer. This paper reviews the latest reports on the potential therapy of skin disorders through treatment with phenolic compounds, considering mostly a single specific compound or a combination of compounds in a plant extract.

447 citations


Cites methods from "Transdermal drug delivery: penetrat..."

  • ...electroporation, iontophoresis, or occlusive dressings) and chemical methods (including, the addition of chemical compounds that interact with components of the skin that cause a reversible modification of disrupting the barrier function and resulting in an increase in its permeability) were developed [93,94]....

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Journal ArticleDOI
TL;DR: A review of zinc oxide nanoparticles destined for use in modern sunscreens and the potential for human exposure and the health hazard at each stage of their manufacture and use is discussed.
Abstract: Sunscreens containing metal oxide nanoparticles appear transparent on the skin and provide excellent protection against sunburn caused by UV radiation. While it is likely that nanoparticles remain ...

367 citations

Journal ArticleDOI
TL;DR: This Review summarizes the current status, latest updates and future prospects for delivery of peptides, proteins and other biologics, including subcutaneous, transdermal, oral, inhalation, nasal and buccal routes.
Abstract: Biologics now constitute a significant element of available medical treatments. Owing to their clinical and commercial success, biologics are a rapidly growing class and have become a dominant therapeutic modality. Although most of the successful biologics to date are drugs that bear a peptidic backbone, ranging from small peptides to monoclonal antibodies (~500 residues; 150 kDa), new biologic modalities, such as nucleotide-based therapeutics and viral gene therapies, are rapidly maturing towards widespread clinical use. Given the rise of peptides and proteins in the pharmaceutical landscape, tremendous research and development interest exists in developing less-invasive or non-invasive routes for the systemic delivery of biologics, including subcutaneous, transdermal, oral, inhalation, nasal and buccal routes. This Review summarizes the current status, latest updates and future prospects for such delivery of peptides, proteins and other biologics.

341 citations

References
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Book
19 Jul 1995

483 citations


"Transdermal drug delivery: penetrat..." refers background in this paper

  • ...Of these, occlusive films of plastic or oily vehicle have the most profound effect on hydration and penetration rate [129, 130]....

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Journal Article
TL;DR: The biochemistry of the skin and its role in assessing potential drug interactions, chemical and electrical attempts to enhance percutaneous absorption and transdermal drug delivery, selection of drug candidates and methods for delivery, and areas requiring further inves are examined.
Abstract: Selected researchers examine the biochemistry of the skin and its role in assessing potential drug interactions, chemical and electrical attempts to enhance percutaneous absorption and transdermal drug delivery, selection of drug candidates and methods for delivery, and areas requiring further inves

276 citations

Book
01 Jan 1993
TL;DR: Water - the most natural penetration enhancer, Michael S. Roberts and Michael Walker simple alkyl esters as skin penetration enhancers, David R. Ward and David W. Osborne molecular modelling of skin permeation enhancement by chemical agents.
Abstract: Water - the most natural penetration enhancer, Michael S. Roberts and Michael Walker simple alkyl esters as skin penetration enhancers, David R. Friend and Jorge Heller phospholipids as skin penetration enhancers, Gary P. Martin terpenes as skin penetration enhancers, Brian W. Barry and Adrian C. Williams mechanisms and prediction of nonionic surfactant effects on skin permeability, Edward J. French et al interaction between anionic surfactants and skin, J. Gordon Black in vitro analysis of QSAR in wanted and unwanted effects of azacycloheptanonesas transdermal penetration enhancers, Harry E. Bodde et al oleyl surfactants as skin penetration enhancers - skin irritation and in vitro toxicity to cultured human skin cells, Harry E. Bodde et al synergistic effects in percutaneous enhancement, Birgitte Mollgaard supersaturated solutions as topical drug delivery systems, Adrian F. Davis and Jonathan Hadgraft infrared spectroscopy of stratum corneum lipids - in vitro results and their relevance to permeability, Russell O. Potts and Michael L. Francoeur the use of ultrasound in skin penetration enhancement, James C. McElnay et al iontophoretic drug delivery, Philip G. Green et al technological aspects of penetration enhancers in transdermal systems, Thomas Hille veterinary applications of skin penetration enhancers, Kenneth A. Walters and Michael S. Roberts hydrotropy and penetration enhancement, Anthony J.I. Ward and David W. Osborne molecular modelling of skin permeation enhancement by chemical agents, Keith R. Brain and Kenneth A. Walters skin penetration enhancement - clinical pharmacological and regulatory considerations, Vinod P. Shaah et al.

196 citations

BookDOI
14 Dec 2007
TL;DR: The relationship between structure and barrier function of skin dermal metabolism systemic toxicity in man secondary to per cutaneous absorption and in vitro measurement of percutaneous absorption investigation of the skin permeation in vitro prediction is studied.
Abstract: The relationship between structure and barrier function of skin dermal metabolism systemic toxicity in man secondary to percutaneous absorption. Part 1 Modelling of dermal risk assessment: occupational skin disease - a case study current issues inthe in vitro measurement of percutaneous absorption investigation of the skin permeation in vitro prediction -physiological models prediction - simple risk models and overview of dermal risk assessment cutaneous microdialysis for human in vivo dermalabsorption studies physicochemical determinants of stratum corneum permeation. Part 2 Pharmeceuticals: in vitro/in vivo correlations in transdermal drug delivery irritancy of topical chemicals and transdermal delivery systems chemical penetrationenhancement - possibilities and problems drugs used for skin diseases drugs for pain and inflammation site of effects iontophoresis topical therapeutic agents used in wound care. Part 3 Cosmetics: regulation of cosmetics in the United States experimental design considerations and use of in vitro skin penetration data in cosmetic risk assessment percutaneous absorption of hair dyes sunscreens - toxicological aspects exposure to fragrances - their absorption and potential toxicity. Part 4Environmental: dermal absorption and toxicity assessment human skin penetration by metal compounds soil contamination -theoretical descriptions percutaneous absorption of hazardous substances from soil and water bathing water - percutaneous absorptionof water contaminants ultrastructural effects of some solvents and vehicles on the stratum corneum and other skin components - evidence for an extended mosaic-partitioning model of the skin barrier.

170 citations

Book
01 Jan 1992
TL;DR: "Percutaneous Penetration Enhancement": Physicochemical Considerations and Implications for Prodrug Design, Richard H. Guy and Jonathan Hadgraft Functional Group Considerations in the Development of Prodrug Approaches to Solving Topical Delivery Problems, Kenneth B. Sloan
Abstract: "Percutaneous Penetration Enhancement: Physicochemical Considerations and Implications for Prodrug Design, Richard H. Guy and Jonathan Hadgraft Functional Group Considerations in the Development of Prodrug Approaches to Solving Topical Delivery Problems, Kenneth B. Sloan Prodrugs for Dermal Delivery: Solubility, Molecular Size, and Functional Group Effects, Gerald B. Kasting, Ronald L. Smith, and Bradley D. Anderson A Computational Method for Predicting Optimization of Prodrugs or Analogues Designed for Percutaneous Delivery, David W. Osborne and William J. Lambert Use of Solubility Parameters from Regular Solution Theory to Describe Partitioning-Driven Processes, Kenneth B. Sloan The Effect of Partitioning and Enzymatic Hydrolysis on the Percutaneous Transport of Lipophilic Prodrugs, Russell O. Potts Improved Ocular Drug Delivery with Prodrugs, Vincent H. L. Lee and Hans Bundgaard "

94 citations