Table 4.

Approaches to ocular delivery of peptides against herpes simplex virus keratitis.

Objectives	Drug/Peptide Used	Type of Formulation	Polymer Used	Membrane/Cell Line/Animal Model	Outcome	Source
To evaluate antimicrobial activity of LL-37.	LL-37	Ophthalmic peptide delivery	-	Human corneal and conjunctival epithelial cells (LL-37 expression study)	Antiviral assay: 500 µg/mL of LL-37 reduced HSV-1 viral load by more than 100-fold compared to the phosphate-buffered saline (PBS) and scrambled peptide.	[82]
To compare the release of LL-37 from nanoparticle–hydrogel corneal implants and human corneal epithelial cell (HCEC)-produced LL-37.	LL-37	Peptide delivery, nanoparticle–hydrogel corneal implants, human corneal epithelial cell (HCEC)-produced LL-37.	-	HCECs	In vitro studies: the viral binding was reduced by LL-37, but the virus was not completely cleared from the already infected cells.	[83]
To identify peptides that bind specifically to heparan sulfate (HS). To investigate their effectiveness in inhibiting HSV-1.	G1 and G2 peptide	Ophthalmic peptide delivery	-	Mouse cornea	In vivo studies: the G1 and G2 peptides significantly reduced the severity of keratitis when administered prophylactically.	[85]
To develop and evaluate G2-C contact lens to lengthen the release of G2-C peptide.	G2-C peptide	Ophthalmic peptide delivery using contact lens.	-	Human cornea epithelial cells (ex vivo virus spread assay), pig corneas (ex vivo study of inhibition of HSV-1), mouse model (in vivo efficacy study)	In vitro release: the release of G2-C was prolonged with the use of the contact lens. In vivo and ex vivo studies: the G2-C lens were effective in inhibiting HSV-1 entry in both ex vivo and in vivo studies.	[87]
To evaluate of the therapeutic efficacy of 1% apoEdp.	apoEdp	Ophthalmic peptide delivery	-	Mouse	In vivo studies: 1% apoEdp was as effective as 1% trifluridine in reducing the incidence and severity of herpes simplex keratitis (HSK). The expression of several proinflammatory cytokines was downregulated compared to the control.	[88]
To evaluate the efficacy of 1% apoEdp against HSV-1 thymidine kinase (TK)-positive and HSV-1 TK negative virus.	apoEdp	Ophthalmic peptide delivery	-	NZW rabbits	In vivo studies: apoEdp was as effective as trifluridine and foscarnet in reducing the severity of keratitis in both TK-positive and TK-negative HSV groups.	[89]
To develop ocular insert for antimicrobial peptide delivery.	hLF 1-11	Ophthalmic peptide delivery		-	hLF 1-11 was found to be stable in a freeze-dried solid matrix of hydroxypropyl methylcellulose (HPMCs) and it released the peptide in sustained manner.	[90]