The Role of In Vitro Skin Models in Optimization of Dermal Drug Delivery

2021 ◽  
pp. 693-714
Author(s):  
Gøril Eide Flaten ◽  
Nataša Škalko-Basnet ◽  
Željka Vanić
Keyword(s):  
Drug Delivery ◽  
Dermal Drug Delivery

scholarly journals Verification of P-Glycoprotein Function at the Dermal Barrier in Diffusion Cells and Dynamic “Skin-On-A-Chip” Microfluidic Device

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 804
Author(s):  
Ágnes Bajza ◽  
Dorottya Kocsis ◽  
Orsolya Berezvai ◽  
András József Laki ◽  
Bence Lukács ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Ex Vivo ◽  
Topical Administration ◽  
Transdermal Absorption ◽  
P Glycoprotein ◽  
Diffusion Cells ◽  
Defensive Role ◽  
Dermal Drug Delivery

The efficacy of transdermal absorption of drugs and the irritation or corrosion potential of topically applied formulations are important areas of investigation in pharmaceutical, military and cosmetic research. The aim of the present experiments is to test the role of P-glycoprotein in dermal drug delivery in various ex vivo and in vitro platforms, including a novel microchip technology developed by Pázmány Péter Catholic University. A further question is whether the freezing of excised skin and age have any influence on P-glycoprotein-mediated dermal drug absorption. Two P-glycoprotein substrate model drugs (quinidine and erythromycin) were investigated via topical administration in diffusion cells, a skin-on-a-chip device and transdermal microdialysis in rat skin. The transdermal absorption of both model drugs was reduced by P-glycoprotein inhibition, and both aging and freezing increased the permeability of the tissues. Based on our findings, it is concluded that the process of freezing leads to reduced function of efflux transporters, and increases the porosity of skin. P-glycoprotein has an absorptive orientation in the skin, and topical inhibitors can modify its action. The defensive role of the skin seems to be diminished in aged individuals, partly due to reduced thickness of the dermis. The novel microfluidic microchip seems to be an appropriate tool to investigate dermal drug delivery.

scholarly journals Role of nasal casts for in vitro evaluation of nasal drug delivery and quantitative evaluation of various nasal casts

2020 ◽  
Vol 11 (8) ◽  
pp. 485-495
Author(s):  
Per G Djupesland ◽  
John C Messina ◽  
Ramy A Mahmoud
Keyword(s):  
Computed Tomography ◽  
Drug Delivery ◽  
Quantitative Evaluation ◽  
Healthy Male ◽  
Nasal Drug Delivery ◽  
Normal Range ◽  
Cross Sectional ◽  
Drug Deposition

Background: Nasal casts may characterize intranasal drug deposition. Methodology: The Koken cast, described as ‘anatomically correct’, and the Optinose cast, derived from MRI of a healthy male during velum closure, were dimensionally compared and assessed for deposition assessment suitability. Results: Smallest vertical cross-sectional areas (valve region) for Koken and Optinose right/left: 2.55/2.75 and 1.18/1.18 cm2, respectively, versus a ‘normative’ mean (range) of 0.85 cm2 (0.2–1.6 cm2). Intranasal volumes differed (computed tomography/water fill): Koken, 35.8/38.6 cm3 and Optinose, 24.1/25.0 cm3, versus a ‘normative’ mean (range) of 26.4 cm3 (20.9–31.1 cm3). Conclusion: Koken cast dimensions are larger than the normal range and the Optinose cast. The validity of casts for regulatory drug deposition studies is suspect.

scholarly journals Reassessing the Role of Intra-Arterial Drug Delivery for Glioblastoma Multiforme Treatment

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Jason A. Ellis ◽  
Matei Banu ◽  
Shaolie S. Hossain ◽  
Rajinder Singh-Moon ◽  
Sean D. Lavine ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Optical Measurements ◽  
Pharmacological Agents ◽  
Cellular Targets ◽  
Therapeutic Landscape ◽  
Rational Drug

Effective treatment for glioblastoma (GBM) will likely require targeted delivery of several specific pharmacological agents simultaneously. Intra-arterial (IA) delivery is one technique for targeting the tumor site with multiple agents. Although IA chemotherapy for glioblastoma (GBM) has been attempted since the 1950s, the predicted benefits remain unproven in clinical practice. This review focuses on innovative approaches to IA drug delivery in treating GBM. Guided by novel in vitro and in vivo optical measurements, newer pharmacokinetic models promise to better define the complex relationship between background cerebral blood flow and drug injection parameters. Advanced optical technologies and tracers, unique nanoparticles designs, new cellular targets, and rational drug formulations are continuously modifying the therapeutic landscape for GBM. Personalized treatment approaches are emerging; however, such tailored approaches will largely depend on effective drug delivery techniques and on the ability to simultaneously deliver multidrug regimens. These new paradigms for tumor-selective drug delivery herald dramatic improvements in the effectiveness of IA chemotherapy for GBM. Therefore, within this context of so-called “precision medicine,” the role of IA delivery for GBM is thoroughly reassessed.

scholarly journals The Use of Ultrasound and Micelles in Cancer Treatment

2008 ◽  
Vol 8 (5) ◽  
pp. 2205-2215 ◽  
Author(s):  
Ghaleb A. Husseini ◽  
William G. Pitt
Keyword(s):  
Drug Delivery ◽  
Polymeric Micelles ◽  
Tumor Model ◽  
Therapeutic Window ◽  
Rat Tumor Model ◽  
Drug Potency ◽  
Potential Benefits

The high toxicity of potent chemotherapeutic drugs like Doxorubicin (Dox) limits the therapeutic window in which they can be applied. This window can be expanded by controlling the drug delivery in both space and time such that non-targeted tissues are not adversely affected. Recent research has shown that ultrasound (US) can be used to control the release of Dox and other hydrophobic drugs from polymeric micelles in both time and space. It has also been shown using an in vivo rat tumor model that Dox activity can be enhanced by ultrasound in one region, while in an adjacent region there is little or no effect of the drug. In this article, we review the in vivo and in vitro research being conducted in the area of using ultrasound to enhance and target micellar drug delivery to cancerous tissues. Additionally, we summarize our previously published mathematical models that attempt to represent the release and re-encapsulation phenomena of Dox from Pluronic® P105 micelles upon the application of ultrasound. The potential benefits of such controlled chemotherapy compels a thorough investigation of the role of ultrasound (US) and the mechanisms by which US accomplishes drug release and/or enhances drug potency. Therefore we will summarize our findings related to the mechanism involved in acoustically activated micellar drug delivery to tumors.

Role of Polyvinylpyrrolidone in Dissolving Microneedle for Efficient Transdermal Drug Delivery: In vitro and Clinical Studies

2018 ◽  
Vol 39 (6) ◽  
pp. 789-793 ◽  
Author(s):  
Woo Sun Shim ◽  
Young Min Hwang ◽  
Sun Gyoo Park ◽  
Cheon Koo Lee ◽  
Nae Gyu Kang
Keyword(s):  
Drug Delivery ◽  
Clinical Studies ◽  
Transdermal Drug Delivery

scholarly journals In Vitro–In Vivo Correlation in Dermal Delivery: The Role of Excipients

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 542
Author(s):  
Avnish Patel ◽  
Fotis Iliopoulos ◽  
Peter J. Caspers ◽  
Gerwin J. Puppels ◽  
Majella E. Lane
Keyword(s):  
Drug Delivery ◽  
Correlation Coefficient ◽  
Skin Permeation ◽  
Pearson Correlation ◽  
Cumulative Number ◽  
Skin Delivery ◽  
Diffusion Studies

The composition of topical and transdermal formulations is known to determine the rate and the extent of drug delivery to and through the skin. However, to date, the role of excipients in these formulations on skin delivery of actives has received little attention from scientists in the field. Monitoring skin absorption of both drug and vehicle may provide insights into the mechanism by which excipients promote permeation and may facilitate the design of effective and safer products. Previously, we have investigated the use of quantitative Confocal Raman Spectroscopy (CRS) to investigate the delivery of an active to the skin, and we also reported the first fully quantitative study that compared this method with the well-established in vitro permeation test (IVPT) model. To further explore the potential of quantitative CRS in assessing topical delivery, the present work investigated the effects of commonly used excipients on the percutaneous absorption of a model drug, ibuprofen (IBU). Permeation of IBU and selected solvents following finite dose applications to human skin was determined in vitro and in vivo by Franz diffusion studies and quantitative CRS, respectively. The solvents used were propylene glycol (PG), dipropylene glycol (DPG), tripropylene glycol (TPG), and polyethylene glycol 300 (PEG 300). Overall, the cumulative amounts of IBU that permeated at 24 h in vitro were similar for PG, DPG, and TPG (p > 0.05). These three vehicles outperformed PEG 300 (p < 0.05) in terms of drug delivery. Concerning the vehicles, the rank order for in vitro skin permeation was DPG ≥ PG > TPG, while PEG 300 did not permeate the skin. A linear relationship between maximum vehicle and IBU flux in vitro was found, with a correlation coefficient (R2) of 0.95. When comparing in vitro with in vivo data, a positive in vitro–in vivo (IVIV) correlation between the cumulative permeation of IBU in vitro and the total amount of IBU that penetrated the stratum corneum (SC) in vivo was observed, with a Pearson correlation coefficient (R2) of 0.90. A strong IVIV correlation, R2 = 0.82, was found following the linear regression of the cumulative number of solvents permeated in vitro and the corresponding skin uptake in vivo measured with CRS. This is the first study to correlate in vivo permeation of solvents measured by CRS with data obtained by in vitro diffusion studies. The IVIV correlations suggest that CRS is a powerful tool for profiling drug and vehicle delivery from dermal formulations. Future studies will examine additional excipients with varying physicochemical properties. Ultimately, these findings are expected to lead to new approaches for the design, evaluation, and optimization of formulations that target actives to and through the skin.

scholarly journals Protein Based Nanostructures for Drug Delivery

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Deepali Verma ◽  
Neha Gulati ◽  
Shreya Kaul ◽  
Siddhartha Mukherjee ◽  
Upendra Nagaich
Keyword(s):  
Drug Delivery ◽  
Drug Loading ◽  
Particle Morphology ◽  
Particle Structure ◽  
In Vitro Drug Release ◽  
Routes Of Administration ◽  
Protein Nanoparticles

The key role of protein based nanostructures has recently revolutionized the nanomedicine era. Protein nanoparticles have turned out to be the major grounds for the transformation of different properties of many conventional materials by virtue of their size and greater surface area which instigates them to be more reactive to some other molecules. Protein nanoparticles have better biocompatibilities and biodegradability and also have the possibilities for surface modifications. These nanostructures can be synthesized by using protein like albumin, gelatin, whey protein, gliadin, legumin, elastin, zein, soy protein, and milk protein. The techniques for their fabrication include emulsification, desolvation, complex coacervation, and electrospray. The characterization parameters of protein nanoparticles comprise particle size, particle morphology, surface charge, drug loading, determination of drug entrapment, and particle structure and in vitro drug release. A plethora of protein nanoparticles applications via different routes of administration are explored and reported by eminent researchers which are highlighted in the present review along with the patents granted for protein nanoparticles as drug delivery carriers.

scholarly journals The role of pharmaceutical nanotechnology in the time of COVID-19 pandemic

2020 ◽  
Vol 15 (16) ◽  
pp. 1571-1582
Author(s):  
Lígia N de M Ribeiro ◽  
Belchiolina B Fonseca
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
In Vitro Toxicity ◽  
Clinical Use ◽  
Therapeutic Action ◽  
High Toxicity ◽  
Pharmaceutical Nanotechnology

There is no effective therapy against COVID-19 available so far. In the last months, different drugs have been tested as potential treatments for COVID-19, exhibiting high toxicity and low efficacy. Therefore, nanotechnology can be applied to improve the therapeutic action and minimize the toxicity of loaded drugs. In this review, we summarized the drugs tested as COVID-19 treatment and the advantages of antiviral nanostructured drug-delivery systems. Such systems have demonstrated low in vitro toxicity with better in vitro antiviral activity than free drugs. We believe that this approach should inspire novel nanostructured drug-delivery systems developments to find efficient COVID-19 treatments. Here, we discuss the remaining challenges for such promising nanosystems to be approved for clinical use.

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