scholarly journals Reconstituted epithelial corneal tissues for evaluation of drug delivery

Author(s):  
Susi Burgalassi ◽  
Erica Zucchetti ◽  
Eleonora Terreni ◽  
Daniela Monti ◽  
Silvia Tampucci ◽  
...  

One possible approach to reduce the use of animals in the evaluation of the ocular drug delivery is that to use cell cultures as model of tissues. In this study are compared two different reconstituted epithelial corneal tissues, a homemade artificial corneal epithelium (Reconstituted Rabbit Corneal Epithelium) and a commercial human corneal epithelial model (COR-100 EpiCornealTM, MatTek), for permeation experiments of three drugs with different physical chemical properties: timolol maleate, cyclosporin A, and a newly synthesized compound, MAGL 17.b. The collected data show that corneal epithelial models are not sufficient to simulate the complexity of the corneal barrier and the presence of a layer simulating the stroma may be necessary to approach the structure of native cornea.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 867
Author(s):  
Carlo Astarita ◽  
Sara Palchetti ◽  
Mina Massaro-Giordano ◽  
Marina Di Domenico ◽  
Francesco Petrillo ◽  
...  

Topical administration is the most convenient route for ocular drug delivery, but only a minor fraction is retained in the precorneal pocket. To overcome this limitation, numerous drug delivery systems (DDS) have been developed. The protein corona (PC) is the layer of biomolecules (e.g., proteins, sugars, lipids, etc.) that forms around DDS in physiological environments by non-covalent interaction. The PC changes the DDS physical–chemical properties, providing them with a completely novel biological identity. The specific involvement of PC in ocular drug delivery has not been addressed so far. To fulfill this gap, here we explored the interaction between a library of four cationic liposome-DNA complexes (lipoplexes) and mucin (MUC), one of the main components of the tear film. We demonstrate that MUC binds to the lipoplex surface shifting both their size and surface charge and reducing their absorption by primary corneal epithelial cells. To surpass such restrictions, we coated lipoplexes with two different artificial PCs made of Fibronectin (FBN) and Val-Gly-Asp (VGA) tripeptide that are recognized by receptors expressed on the ocular surface. Both these functionalizations remarkedly boosted internalization in corneal epithelial cells with respect to pristine (i.e., uncoated) lipoplexes. This opens the gateway for the exploitation of artificial protein corona in targeted ocular delivery, which will significantly influence the development of novel nanomaterials.


2020 ◽  
Vol 59 (1) ◽  
pp. 441-454
Author(s):  
Carlos A. Martínez-Pérez

AbstractIn the last years, electrospinning has become a technique of intense research to design and fabricate drug delivery systems (DDS), during this time a vast variety of DDS with mainly electrospun polymers and many different active ingredient(s) have been developed, many intrinsic and extrinsic factor have influence in the final system, there are those that can be attributed to the equipment set up and that to the physical-chemical properties of the used materials in the fabrication of DDS. After all, this intense research has generated a great amount of DDS loaded with one or more drugs. In this manuscript a review with the highlights of different kind of systems for drug delivery systems is presented, it includes the basic concepts of electrospinning, types of equipment set up, polymer/drug systems, limitations and challenges that need to be overcome for clinical applications.


Applied Nano ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 118-127
Author(s):  
Luca Zoia ◽  
Anna Binda ◽  
Laura Cipolla ◽  
Ilaria Rivolta ◽  
Barbara La Ferla

Binary nano-biocomposite 3D scaffolds of cellulose nanocrystals (CNCs)—gelatine were fabricated without using chemical crosslinking additives. Controlled oxidative treatment allowed introducing carboxyl or carbonyl functionalities on the surface of CNCs responsible for the crosslinking of gelatine polymers. The obtained composites were characterized for their physical-chemical properties. Their biocompatibility towards different cell cultures was evaluated through MTT and LDH assays, cellular adhesion and proliferation experiments. Gelatine composites reinforced with carbonyl-modified CNCs showed the most performing swelling/degradation profile and the most promising adhesion and proliferation properties towards cell lines, suggesting their potential application in the field of tissue engineering.


2003 ◽  
Vol 31 (4) ◽  
pp. 409-417 ◽  
Author(s):  
Anne Huhtala ◽  
Sami K. Nurmi ◽  
Hanna Tähti ◽  
Lotta Salminen ◽  
Päivi Alajuuma ◽  
...  

Alternatives to the Draize rabbit eye irritation test are currently being investigated. Because of morphological and biochemical differences between the rabbit and the human eye, continuous human cell lines have been proposed for use in ocular toxicology studies. Single cell-type monolayer cultures in culture medium have been used extensively in ocular toxicology. In the present study, an SV40-immortalised human corneal epithelial (HCE) cell line was characterised immunohistochemically, by using 13 different monoclonal antibodies to cytokeratins (CKs), ranging from CK3 to CK20. The results from the monolayer HCE cell cultures were compared with those from the corneal epithelium of human corneal cryostat sections. Previous studies have shown that the morphology of the HCE cell is similar to that of primary cultured human corneal epithelial cells, and that the cells express the cornea-specific CK3. In the study reported here, we show that the cell line also expresses CKs 7, 8, 18 and 19. These CKs are typically expressed by simple epithelial cells, and are not found in the human cornea in vivo. Therefore, the monolayer HCE cell line grown in culture medium does not express the CK pattern that is typical of human corneal epithelium. This should be taken into consideration when using HCE cell cultures in similar single cell-type experiments for ocular toxicology.


2009 ◽  
Vol 10 (2) ◽  
pp. 540-546 ◽  
Author(s):  
Himanshu Gupta ◽  
M. Aqil ◽  
R. K. Khar ◽  
Asgar Ali ◽  
Aseem Bhatnagar ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2142
Author(s):  
Alejandro Sosnik ◽  
Ronya Ben Shabo ◽  
Hen Moshe Halamish

Ocular drug delivery is challenging due to the very short drug residence time and low permeability. In this work, we produce and characterize mucoadhesive mixed polymeric micelles (PMs) made of chitosan (CS) and poly(vinyl alcohol) backbones graft-hydrophobized with short poly(methyl methacrylate) blocks and use them to encapsulate cannabidiol (CBD), an anti-inflammatory cannabinoid. CBD-loaded mixed PMs are physically stabilized by ionotropic crosslinking of the CS domains with sodium tripolyphoshate and spray-drying. These mixed PMs display CBD loading capacity of 20% w/w and sizes of 100–200 nm, and spherical morphology (cryogenic-transmission electron microscopy). The good compatibility of the unloaded and CBD-loaded PMs is assessed in a human corneal epithelial cell line. Then, we confirm the permeability of CBD-free PMs and nanoencapsulated CBD in human corneal epithelial cell monolayers under liquid–liquid and air–liquid conditions. Overall, our results highlight the potential of these polymeric nanocarriers for ocular drug delivery.


Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1534 ◽  
Author(s):  
Pasquale Sacco ◽  
Michela Cok ◽  
Francesca Scognamiglio ◽  
Chiara Pizzolitto ◽  
Federica Vecchies ◽  
...  

Chitosan derivatives, and more specifically, glycosylated derivatives, are nowadays attracting much attention within the scientific community due to the fact that this set of engineered polysaccharides finds application in different sectors, spanning from food to the biomedical field. Overcoming chitosan (physical) limitations or grafting biological relevant molecules, to mention a few, represent two cardinal strategies to modify parent biopolymer; thereby, synthetizing high added value polysaccharides. The present review is focused on the introduction of oligosaccharide side chains on the backbone of chitosan. The synthetic aspects and the effect on physical-chemical properties of such modifications are discussed. Finally, examples of potential applications in biomaterials design and drug delivery of these novel modified chitosans are disclosed.


2010 ◽  
Vol 660-661 ◽  
pp. 794-798 ◽  
Author(s):  
Maria Graças da Silva-Valenzuela ◽  
Shu Hui Wang ◽  
Helio Wiebeck ◽  
Francisco Rolando Valenzuela-Díaz

Drug delivery systems involving microcapsules provide an attractive way to improve the performance of many chemical and biological substances. These systems may be used for several industrial segments, especially medical, pharmaceuticals and cosmetics. PHB is a polyhydroxyalkanoate available in powder form, biocompatible, biodegradable and inert towards animal tissues. The obtained PHB/smectite clay nanocomposite improved the physical-chemical properties of PHB, including its biodegradability. In this work, we describe the preparation of microcapsules from two nanocomposites systems: a) PHB and Cloisite 20A organoclay (PHB1) and b) PHB and natural Brazilian green policationic clay (PHB2). When analyzed by XRD, the films and microcapsules did not show a d(001) peak, demonstrating an exfoliated structure for the nanocomposites. The films have shown by SEM an homogeneous distribution with the clay mineral particles spread homogeneously by the PHB film. The new microcapsules/nanocomposites showed an “hydrangea” morphology. The diameter of the microcapsules was variable between 0.5-15 µm.


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