Table 3.
Prodrug approach for ocular drug delivery against herpes keratitis.
| Objectives | Drug | Type of Formulation | Polymer Used | Membrane/Cell Line/Animal Model | Outcome | Source |
|---|---|---|---|---|---|---|
| To evaluate the corneal absorption of amino acid prodrugs. | Acyclovir (ACV) | Ophthalmic prodrug | - | Primary corneal epithelial cell cultures | Stability: L-Serine-ACV (SACV) was the most stable among the other prodrugs. In vivo ocular absorption: SACV and L-Valine- ACV (VACV) showed a 2-fold increase in area under concentration time curve (AUC) and maximum aqueous humor concentration (Cmax) of prodrug and regenerated ACV compared to ACV. Cytotoxicity studies: cellular toxicity of ACV prodrugs was significant lower compared to trifluridine. |
[73] |
| To characterise the amino acid prodrugs based on affinity and permeability. | Acyclovir | Ophthalmic prodrug | - | Rabbit primary corneal epithelial cell culture (rPCEC) | In vitro antiviral studies: SACV displayed anti-HSV-1 activity and the concentration required to inhibit viral cytopathogenicity by 50% (EC50) was 6.3 μM. Corneal permeability: SACV exhibited higher corneal permeability and superior anti-HSV-1 activity relative to ACV. |
[74] |
| To evaluate dipeptide monoester ganciclovir (GCV) prodrugs. | Ganciclovir (GCV) | Ophthalmic prodrug | - | New Zealand White (NZW) rabbits | Solubility: the prodrugs showed better aqueous solubility compared to parent drug. Transcorneal permeability: valine-GCV (VGCV) and divaline-GCV (VVGCV) were 7- to 8-fold higher than GCV. In vivo efficacy studies: 1% VVGCV has better therapeutic activity against HSV-1 epithelial keratitis compared to 1% trifluridine. |
[75] |
| To evaluate the corneal absorption of dipeptide monoester prodrugs. | Ganciclovir | Ophthalmic prodrug | - | NZW rabbits | In vivo studies: The area under the concentration–time profile (AUCinfinity)of the regenerated GCV from tyrosine-valine-GCV (YVGCV) was 8.6-fold higher than GCV, whereas VVGCV was 1.8-fold higher than GCV. Both YVGCV and VVGCV demonstrated enhanced permeability and superior corneal absorption. |
[76] |
| To develop sodium-dependent multivitamin transporter (SMVT)-targeted biotinylated lipid prodrugs to improve cellular absorption. | Acyclovir | Ophthalmic prodrug | - | Human corneal epithelial cells (HCECs) | Uptake study: the uptake of biotin-ricinoleicacid-acyclovir (B-R-ACV) and biotin-12hydroxystearicacid-acyclovir (B-12HS-ACV) was nearly 13.6-fold and 13.1-fold higher than parent drug, respectively. Stability: B-R-ACV and B-12HS-ACV possessed better stability. In vitro antiviral activity: B-R-ACV: ~4.5-fold and 8.7-fold more potent against HSV-1 and HSV-2, respectively, compared to parent drug. B-12HS-ACV: ~200-fold and 21-fold more potent against HSV-1 and HSV-2, respectively, compared to parent drug. |
[77] |