Table 5.
Smart ocular delivery using in situ gel approach against ocular diseases.
| Objective | Drug | Types of Stimuli/Polymer Used | Membrane/Cell Line/Animal Model | Outcome | Source |
|---|---|---|---|---|---|
| Preparation of ocular in situ micelles to enhance ocular permeation. | Acyclovir | Thermo-responsive micelles/Soluplus | Rabbits | Higher corneal and sclera permeability compared to conventional formulation. | [54] |
| Preparation and evaluation of ion-activated in situ gel ophthalmic delivery system of acyclovir based on kappa-carrageenan. | Acyclovir- hydroxypropyl-β-cyclodextrin complex | Ion-activated/kappa-carrageenan | New Zealand White (NZW) rabbits | Rheology: pseudoplastic fluid Gelling capacity: gel formed rapidly after contact with tear fluid, maintained for a long time. In vitro release: 80% of drug released after 6 h In vitro permeability: 2.16-fold higher apparent permeability. In vivo irritation: no irritation to rabbits’ eyes. |
[95] |
| To develop sustained release nanoparticles loaded with ganciclovir prodrug. | Ganciclovir prodrug | Thermo-responsive/poly (lactic-co-glycolic acid) (PLGA), PLGA-polyethylene glycol-PLGA (PLGA-PEG-PLGA) | Human corneal epithelial cells (HCECs) | NPs were small in size with higher drug loading and entrapment. Biphasic release pattern: burst release followed by sustained release. Efficient permeation of prodrug with accumulation in cul-de-sac. |
[93] |
| To develop and evaluate thermo-responsive in situ gel nanoemulsions in delivering acyclovir. | Acyclovir (ACV) | Thermo-responsive nanoemulsion/Triacetin and Transcutol® P (nanoemulsion) poloxamer 407 and poloxamer 188 (in situ) |
NZW rabbits (in vivo ocular irritation test) and Hen’s Egg-Chorioallantoic Membrane (HET-CAM) (in vitro ocular irritation test) |
Gelation temperature 30.9 °C. pH: 4.58 ± 0.068 Viscosity: 103.03 ± 4.68 mPa.s In vitro drug release efficiency: 80.78 ± 1.82% The optimised formulations displayed sustained release. Ex vivo permeation: permeation of ACV was 2.83-fold higher in optimised formulation compared to ACV solution. In vivo ocular irritation test: minimal conjunctival redness but disappeared after 2 h of administration. In vitro ocular irritation (HET-CAM) test: cumulative score of 0.33 ± 0.58, indicating non-irritant |
[94] |
| To design polymeric nanoparticles of acyclovir incorporated in in situ gelling system to provide dual sustained release effect, whereby the duration of action and bioavailability through different routes of administration could be improved. | Acyclovir | Thermo-activated/Pluronic F-127 and pH-activated/Carbopol |
- | Gelation temperature: 25 ± 0.20 to 35 ± 0.46 °C Gelation time: 2 to 4 min In vitro drug release study: better sustained release characteristics, with non-Fickian diffusion mechanism of drug release. |
[96] |
| Formulation of valcyclovir in situ gels. | Valcyclovir | pH-activated/Carbopol 940, HPMC K 100M | - | In situ gels show sustained release with profile. | [98] |
| Development of acyclovir-loaded niosomes entrapped in hydrogel | Acyclovir | pH-activated/Span 20 or Span 60, cholesterol, Carbopol 934, methylcellulose | Rabbits | Sustained release with no sign of irritation | [99] |