Alternative Methods to Animal Testing on the Assessment of Drug Permeation Across Different Barriers, Focusing on the Skin and Eye

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biopharmaceutics".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 5499

Special Issue Editors


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Guest Editor
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
Interests: pharmaceutical formulation development and evaluation, ocular drug delivery, mucosal drug delivery, mucoadhesive formulations
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Assistant Guest Editor
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
Interests: pharmaceutical formulation; ocular drug delivery

Special Issue Information

Dear Colleagues,

The number of animals used in research has significantly increased with the advancement of sciences and the development of medical technology. This has led to an increasing demand and implementation of alternatives approaches that can partially or entirely replace laboratory animals, also in line with the guiding principles of the 3Rs (Replacement, Reduction, and Refinement).

Mainly, there are two alternatives to in vivo animal testing: the use of cell culture to develop 2D assays or more complex 3D structures and the application of in silico computer simulations.

The development of new drugs or delivery systems involves a plethora of tests on animals, including assays to evaluate the ability of molecules to permeate membranes and tissues of our body.

This Special Issue will focus on in vitro and in silico alternative methods to the use of animals for drug permeation studies across the ocular and cutaneous barriers.

Prof. Dr. Susi Burgalassi
Ms. Erica Zucchetti
Guest Editors

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Keywords

  • alternative methods
  • permeation
  • cell cultures
  • computer simulation
  • cornea model
  • ocular barrier
  • cutaneous barrier
  • skin model

Published Papers (2 papers)

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19 pages, 2778 KiB  
Article
Hydrogels as Corneal Stroma Substitutes for In Vitro Evaluation of Drug Ocular Permeation
by Susi Burgalassi, Erica Zucchetti, Leonardo Ling, Patrizia Chetoni, Silvia Tampucci and Daniela Monti
Pharmaceutics 2022, 14(4), 850; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14040850 - 13 Apr 2022
Cited by 3 | Viewed by 2022
Abstract
Hydrogels are complex hydrophilic structures, consisting of crosslinked homopolymers or copolymers insoluble in water. Due to their controllable bio-physicochemical properties mimicking the morphology of the native extracellular matrix, they are a key part of a lot of research fields, including medicine, pharmaceutics, and [...] Read more.
Hydrogels are complex hydrophilic structures, consisting of crosslinked homopolymers or copolymers insoluble in water. Due to their controllable bio-physicochemical properties mimicking the morphology of the native extracellular matrix, they are a key part of a lot of research fields, including medicine, pharmaceutics, and tissue engineering. This paper was focused on the preparation and characterization of hydrogels from different blends of polyvinyl alcohol (PVA) with microcrystalline cellulose (MCC) and gelatin (GEL) at various ratios, and from gelatin and chitosan alone to understand their feasibility of utilizing as corneal stroma substitutes in permeability tests for drug candidate molecules in early stages of their development. The characterization was carried out by differential scanning calorimetry, electron microscopy (SEM), water content, mass loss, water permeability, wettability, and tensile stress–strain tests. After the physicochemical characterization, PVA/MCC blend and chitosan proved to be the most promising constructs, showing negligible mass loss after immersion in aqueous medium for two weeks and low hydrodynamic permeability. They were then employed in drug molecules permeation studies and these data were compared to that obtained through excised tissues. The results obtained showed that PVA/MCC hydrogels have similar mechanical and permeability properties to corneal stroma. Full article
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12 pages, 2955 KiB  
Article
Optimisation of the Chicken Chorioallantoic Membrane Assay in Uveal Melanoma Research
by Ekaterina A. Sokolenko, Utta Berchner-Pfannschmidt, Saskia C. Ting, Kurt W. Schmid, Nikolaos E. Bechrakis, Berthold Seitz, Theodora Tsimpaki, Miriam Monika Kraemer and Miltiadis Fiorentzis
Pharmaceutics 2022, 14(1), 13; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14010013 - 22 Dec 2021
Cited by 16 | Viewed by 2815
Abstract
The treatment of uveal melanoma and its metastases has not evolved sufficiently over the last decades in comparison to other tumour entities, posing a great challenge in the field of ocular oncology. Despite improvements in the conventional treatment regime and new discoveries about [...] Read more.
The treatment of uveal melanoma and its metastases has not evolved sufficiently over the last decades in comparison to other tumour entities, posing a great challenge in the field of ocular oncology. Despite improvements in the conventional treatment regime and new discoveries about the genetic and molecular background of the primary tumour, effective treatment strategies to either prevent tumours or treat patients with advanced or metastatic disease are still lacking. New therapeutic options are necessary in order to achieve satisfactory local tumour control, reduce the risk of metastasis development, and preserve the eyeball and possibly the visual function of the eye. The development of in vivo model systems remains crucial for the identification and investigation of potential novel treatment modalities. The aim of this study was the optimisation of the chorioallantoic membrane (CAM) model for uveal melanoma research. We analysed the established CAM assay and its modification after the implantation of three-dimensional spheroids. The chorioallantoic membrane of a chick embryo was used to implant uveal melanoma-cell-line-derived spheroids in order to study their growth rate, angiogenic potential, and metastatic capability. Using the UM 92.1, UPMD2, UPMM3, and Mel270 cell lines, we were able to improve the viability of the embryos from 20% to >80% and to achieve up to a fourfold volume increase of the transplanted spheroid masses. The results point to the value of an optimised chicken embryo assay as an in vivo model for testing novel therapies for uveal melanoma by simplifying the research conditions and by contributing to a considerable reduction in animal experiments. Full article
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