Abstract
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.
Highlights
IntroductionPoorly permeable and instable drugs into drug delivery systems (DDS) has long been the most efficient way to increase their bioavailability [1]
We have demonstrated that interaction with MUC changes the physical–chemical properties of lipoplexes and provide them with a totally new biological identity
The inversion of the lipoplexes surface charge is likely to reduce the electrostatic interactions within corneal epithelial cells; the MUC layer at the particle surface was responsible for inhibition of cellular internalization, shedding light on the possible inhibitory role of mucins for ocular drugs absorption, which is still not clear
Summary
Poorly permeable and instable drugs into drug delivery systems (DDS) has long been the most efficient way to increase their bioavailability [1]. Nanotechnology has continuously offered new solutions for drug delivery such as the possibility to reduce toxicity and increase the therapeutic index of conventional parent drugs. Since 1995, almost 50 nano-pharmaceuticals have received approval by the Food and Drug Administration (FDA) and are currently available for clinical use [2]. Liposomes are the most successful DDS with a dozen approved drug products and many more in clinical development [3,4].
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