Fabrication and Evaluation of Ketorolac Loaded Cubosome for Ocular Drug Delivery

Abstract

Ophthalmic formulations in terms of eye drops are more frequently used formulation for ocular disorders. But unfortunately this mode of drug instillation into the cul-de-sac of eye shows very poor ocular bioavailability (less than 5%). A large number of carrier systems have been investigated to overcome this problem. In the present study a novel nano-carrier system (Ketorolac loaded cubosomes) is developed and evaluated for the safe and enhance ocular bioavailability. Cubosomes were developed and optimized by utilizing glyceryl monooleate, poloxamer 407 and initial drug concentration. Finally developed formulation was evaluated for various In vitro characteristics i.e. particles size, size distribution, shape and morphology, in-vitro release profile, corneal permeation, corneal retention, and ocular tolerance study. The optimized drug loaded cubosomal formulation showed mean particle size, polydispersity index, and entrapment efficiency 127.3±12.23 nm, 0.205±0.011, and 53.27±5.23 %, respectively. Transmission electron microscopic analysis revealed a cubic shape of developed formulation. Further, developed formulation exhibited biphasic release profile. Significant high transcorneal permeation (2.07 folds) and corneal retention (2.24 folds) of ketorolac was observed with cubosomal formulation correspond to Ketorolac solution (p<0.01). Further safety profile of optimized formulation was evaluated by histopathology of corneal membrane. The developed novel ocular carrier system (cubosomes) might be a promising platform as a vehicle for effective ocular drug delivery.

Ocular delivery of natamycin based on monoolein/span 80/poloxamer 407 nanocarriers for the effectual treatment of fungal keratitis

“…The cross-polarized images are used to study gross morphology of the particles formed and to rule out whether a cubic or hexagonal symmetrical structure is formed. As reported in literature mesophasic cubic structures are isotropic and produce no birefringence thus black background particle images are seen when observed under a cross polarizer, our findings were similar to the reported results [16]. Thus, PLM images confirm the formation of cubosomes.…”

“…Furthermore, the release studies were subjected to kinetic modelling to find the bestfit release model. The release pattern from cubosome nanoparticle was found to be a bifunctionality process with an initial burst release followed by slower sustained release up to 8 h. The burst release is due to the drug adsorbed onto the outer layer of the cubosome nanoparticles and this is necessary for building sufficient levels of drug in the cornea to kill the microbes immediately after administration into the eye [16,17]. Prolonged-release of natamycin from cubosomes was ascribed to the sustained release property of lipidic surfactants and is also contributed by its mucoadhesion ability [16].…”

“…The samples were negatively stained in 1%(w/v) phosphotungstic acid (3-5 min) [16]. A droplet (5-μl) of the optimized cubosome suspension was positioned onto a 300 mesh carbon coated copper grid and was allowed to settle (3-5 min).…”

Cubosomes: composition, preparation, and drug delivery applications.

“…Utilizing their benefits of being biodegradable, able to encapsulate all 3 types of drug molecules as hydrophilic, hydrophobic and amphiphilic, and they render bioactive agents with targeted release and controlled release [9]. They are found to improve ocular bioavailability of the loaded drugs because they have long residence time at the corneal surface and characterized by mucoadhesive properties due to the presence of GMO leading to improve corneal permeability and consequently improve ocular bioavailability of the incorporated drugs [49]. Interesting results were obtained when cubosomes were studied as a topical ocular drug delivery systems.…”

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“…Histopathology study revealed that ketorolac loaded cubosomes were safe for ocular use. In conclusion, from the studies in ophthalmic drug delivery using cubosomes, it is obvious that this system can be used as a promising vehicle for effective ocular drug delivery 96 .…”