1,721,023 research outputs found
Skin permeabilization for transdermal drug delivery: recent advances and future prospects
Full text linkIntroduction: Transdermal delivery has potential advantages over other routes of administration. It could reduce first-pass metabolism associated with oral delivery and is less painful than injections. However, the outermost layer of the skin, the stratum corneum (SC), limits passive diffusion to small lipophilic molecules. Therefore, methods are needed to safely permeabilize the SC so that ionic and larger molecules may be delivered transdermally.
Areas covered: This review focuses on low-frequency sonophoresis, microneedles, electroporation and iontophoresis, and combinations of these methods to permeabilize the SC. The mechanisms of enhancements and developments in the last 5 years are discussed. Potentially high-impact applications, including protein delivery, vaccination and sensing are presented. Finally, commercial interest and clinical trials are discussed.
Expert opinion: Not all permeabilization methods are appropriate for all applications. Focused studies into applications utilizing the advantages of each method are needed. The total dose and kinetics of delivery must be considered. Vaccination is one application where permeabilization methods could make an impact. Protein delivery and analyte sensing are also areas of potential impact, although the amount of material that can be delivered (or extracted) is of critical importance. Additional work on the miniaturization of these technologies will help to increase commercial interest.National Institutes of Health (U.S.) (NIH grant EB-00351
Low-Frequency Sonophoresis: Application to the Transdermal Delivery of Macromolecules and Hydrophilic Drugs
Full text linkImportance of the field: Transdermal delivery of macromolecules provides an attractive alternative route of drug administration when compared to oral delivery and hypodermic injection because of its ability to bypass the harsh gastrointestinal tract and deliver therapeutics non-invasively. However, the barrier properties of the skin only allow small, hydrophobic permeants to traverse the skin passively, greatly limiting the number of molecules that can be delivered via this route. The use of low-frequency ultrasound for the transdermal delivery of drugs, referred to as low-frequency sonophoresis (LFS), has been shown to increase skin permeability to a wide range of therapeutic compounds, including both hydrophilic molecules and macromolecules. Recent research has demonstrated the feasibility of delivering proteins, hormones, vaccines, liposomes and other nanoparticles through LFS-treated skin. In vivo studies have also established that LFS can act as a physical immunization adjuvant. LFS technology is already clinically available for use with topical anesthetics, with other technologies currently under investigation.
Areas covered in this review: This review provides an overview of mechanisms associated with LFS-mediated transdermal delivery, followed by an in-depth discussion of the current applications of LFS technology for the delivery of hydrophilic drugs and macromolecules, including its use in clinical applications.
What the reader will gain: The reader will gain an insight into the field of LFS-mediated transdermal drug delivery, including how the use of this technology can improve on more traditional drug delivery methods.
Take home message: Ultrasound technology has the potential to impact many more transdermal delivery platforms in the future due to its unique ability to enhance skin permeability in a controlled manner.National Institutes of Health (U.S.) (Grant EB-00351)Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Grant DAAD-19-02-D-002
Ultrasound-enhanced transdermal delivery: recent advances and future challenges
No full textThe skin is a formidable diffusion barrier that restricts passive diffusion to small (<500 Da) lipophilic molecules. Methods used to permeabilize this barrier for the purpose of drug delivery are maturing as an alternative to oral drug delivery and hypodermic injections. Ultrasound can reversibly and non-invasively permeabilize the diffusion barrier posed by the skin. This review discusses the mechanisms of ultrasound-permeability enhancement, and presents technological innovations in equipment miniaturization and recent advances in permeabilization capabilities. Additionally, potentially exciting applications, including protein delivery, vaccination, gene therapy and sensing of blood analytes, are discussed. Finally, the future challenges and opportunities associated with the use of ultrasound are discussed. It is stressed that developing ultrasound for suitable applications is key to ensure commercial success.National Institutes of Health (U.S.) (Grant EB-00351)National Institutes of Health (U.S.) (Grant CA014051)Swiss National Science Foundation (Grant PA002_14059
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Transport Pathways and Enhancement Mechanisms within Localized and Non-Localized Transport Regions in Skin Treated with Low-Frequency Sonophoresis and Sodium Lauryl Sulfate
Full text linkRecent advances in transdermal drug delivery utilizing low-frequency sonophoresis (LFS) and sodium lauryl sulfate (SLS) have revealed that skin permeability enhancement is not homogenous across the skin surface. Instead, highly perturbed skin regions, known as localized transport regions (LTRs), exist. Despite these findings, little research has been conducted to identify intrinsic properties and formation mechanisms of LTRs and the surrounding less-perturbed non-LTRs. By independently analyzing LTR, non-LTR, and total skin samples treated at multiple LFS frequencies, we found that the pore radii (r[subscript pore]) within non-LTRs are frequency-independent, ranging from 18.2 to 18.5 Å, but significantly larger than r[subscript pore] of native skin samples (13.6 Å). Conversely, r[subscript pore] within LTRs increase significantly with decreasing frequency from 161 to 276 Å and to ∞ (>300 Å) for LFS/SLS-treated skin at 60, 40, and 20 kHz, respectively. Our findings suggest that different mechanisms contribute to skin permeability enhancement within each skin region. We propose that the enhancement mechanism within LTRs is the frequency-dependent process of cavitation-induced microjet collapse at the skin surface, whereas the increased r[subscript pore] values in non-LTRs are likely due to SLS perturbation, with enhanced penetration of SLS into the skin resulting from the frequency-independent process of microstreaming
A physical mechanism to explain the delivery of chemical penetration enhancers into skin during transdermal sonophoresis — Insight into the observed synergism
Full text linkThe synergism between low-frequency sonophoresis (LFS) and chemical penetration enhancers (CPEs), especially surfactants, in transdermal enhancement has been investigated extensively since this phenomenon was first observed over a decade ago. In spite of the identifying that the origin of this synergism is the increased penetration and subsequent dispersion of CPEs in the skin in response to LFS treatment, to date, no mechanism has been directly proposed to explain how LFS induces the observed increased transport of CPEs. In this study, we propose a plausible physical mechanism by which the transport of all CPEs is expected to have significantly increased flux into the localized-transport regions (LTRs) of LFS-treated skin. Specifically, the collapse of acoustic cavitation microjets within LTRs induces a convective flux. In addition, because amphiphilic molecules preferentially adsorb onto the gas/water interface of cavitation bubbles, amphiphiles have an additional adsorptive flux. In this sense, the cavitation bubbles effectively act as carriers for amphiphilic molecules, delivering surfactants directly into the skin when they collapse at the skin surface as cavitation microjets. The flux equations derived for CPE delivery into the LTRs and non-LTRs during LFS treatment, compared to that for untreated skin, explain why the transport of all CPEs, and to an even greater extent amphiphilic CPEs, is increased during LFS treatment. The flux model is tested with a non-amphiphilic CPE (propylene glycol) and both nonionic and ionic amphiphilic CPEs (octyl glucoside and sodium lauryl sulfate, respectively), by measuring the flux of each CPE into untreated skin and the LTRs and non-LTRs of LFS-treated skin. The resulting data shows very good agreement with the proposed flux model.National Institutes of Health (U.S.) (Grant EB-00351)Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Grant DAAD-19-02-D-002
Application of the Aqueous Porous Pathway Model to Quantify the Effect of Sodium Lauryl Sulfate on Ultrasound-Induced Skin Structural Perturbation
Full text linkThis study investigated the effect of sodium lauryl sulfate (SLS) on skin structural perturbation when utilized simultaneously with low-frequency sonophoresis (LFS). Pig full-thickness skin (FTS) and pig split-thickness skin (STS) treated with LFS/SLS and LFS were analyzed in the context of the aqueous porous pathway model to quantify skin perturbation through changes in skin pore radius and porosity-to-tortuosity ratio (ε/τ). In addition, skin treatment times required to attain specific levels of skin electrical resistivity were analyzed to draw conclusions about the effect of SLS on reproducibility and predictability of skin perturbation. We found that LFS/SLS-treated FTS, LFS/SLS-treated STS, and LFS-treated FTS exhibited similar skin perturbation. However, LFS-treated STS exhibited significantly higher skin perturbation, suggesting greater structural changes to the less robust STS induced by the purely physical enhancement mechanism of LFS. Evaluation of ε/τ values revealed that LFS/SLS-treated FTS and STS have similar transport pathways, whereas LFS-treated FTS and STS have lower ε/τ values. In addition, LFS/SLS treatment times were much shorter than LFS treatment times for both FTS and STS. Moreover, the simultaneous use of SLS and LFS not only results in synergistic enhancement, as reflected in the shorter skin treatment times, but also in more predictable and reproducible skin perturbation.National Institutes of Health (U.S.) (Grant EB-00351)Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Grant DAAD-19-02-D-002)National Science Foundation (U.S.). Graduate Research Fellowship Progra
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