Development of a convenient ex vivo model for the study of the transcorneal permeation of drugs: histological and permeability evaluation.
In this paper, an ex vivo model for the study of the transcorneal permeation of drugs, based on porcine tissues, was evaluated. The setup is characterized by ease of realization, absence of O₂ and CO₂ bubbling and low cost; additionally, the large availability of porcine tissue permits a high throughput. Histological images showed the comparability between porcine and human corneas and confirmed the effectiveness of the isolation procedure. A new de-epithelization procedure based on a thermal approach was also set up to simulate cornea permeability in pathological conditions. The procedure did not affect the integrity of the underlying layers and allowed the characterization of the barrier properties of epithelium and stroma. Six compounds with different physicochemical properties were tested: fluorescein, atenolol, propranolol, diclofenac, ganciclovir and lidocaine. The model highlighted the barrier function played by epithelium toward the diffusion of hydrophilic compounds and the permselectivity with regard to more lipophilic molecules. In particular, positively charged compounds showed a significantly higher transcorneal permeability than negatively charged compounds. The comparability of results with literature data supports the goodness and the robustness of the model, especially taking into account the behavior of fluorescein, which is generally considered a marker of tissue integrity.
Interdepartmental Center Biopharmanet-TEC, University of Parma, Parma, 43124, Italy.
Silvia
S
Pescina
Paolo
P
Govoni
Arianna
A
Potenza
Cristina
C
Padula
Patrizia
P
Santi
Sara
S
Nicoli
D000003:Abattoirs; D060433:Administration, Ophthalmic; D000818:Animals; D055598:Chemical Phenomena; D003315:Cornea / Q000166:cytology / Q000378:metabolism*; D003319:Corneal Stroma / Q000166:cytology / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D019573:Epithelium, Corneal / Q000502:physiology; D057166:High-Throughput Screening Assays; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D007700:Kinetics; D008954:Models, Biological; D065587:Ocular Absorption; D010539:Permeability; D013045:Species Specificity; D034421:Sus scrofa
D015507:Drugs, Investigational
drug transport; epithelial delivery/permeability; in vitro model; mucosal drug delivery; ocular delivery; permeability; permselectivity; porcine cornea; transcorneal