A potential nanoparticle-loaded in situ gel for enhanced and sustained ophthalmic delivery of dexamethasone

Abstract

Increasing the permeability of drugs across the cornea is key to improving drug absorption by the eye. This study presents a newly developed in situ gel loaded with nanoparticles, which could achieve controlled drug release and high ocular drug bioavailability by avoiding rapid precorneal clearance. The physicochemical parameters of the formulation were investigated and showed uniform size, physical stability, and favorable rheological and gelling properties. Ex vivo permeation studies revealed significantly higher drug release from the in situ gel loaded with nanoparticles compared to the conventional poloxamer in situ gel and the drug solution. When compared with a marketed formulation, the in situ gel loaded with nanoparticles provided slower controlled release and higher ocular bioavailability of dexamethasone. In conclusion, the developed nanoparticle-loaded in situ gel can successfully increase drug ocular bioavailability by enhancing contact time with the ocular surface and permeation through the cornea.

Advances and limitations of drug delivery systems formulated as eye drops

“…Chitosan-HA NPs loaded in chitosan in situ gels exhibited a sustained delivery of 5-fluorouracil in rabbit aqueous humor compared to NPs or in situ gels only solution [133]. Improved drug penetration was also observed for albumin NPs loaded in poloxamer ® gel [135], poloxamer NPs loaded in poloxamer ® gel [136] and Eudragit ® NPs loaded in poloxamer ® /HPMC gel [137], PLGA-Eudragit ® and PCL-Eudragit ® loaded in Carbopol ® gel [139] and liposomes loaded in HA gel [140]. Compared to NPs or in situ gels only, their combination allowed to avoid a burst release and sustain the drug delivery to the aqueous humor (Fig.…”

“…Cmax was found 8.73-fold and 10.06-fold higher for PLGA-Eudragit NPs-gel and PCL-Eudragit NPs-gel, respectively, compared with in situ gel. [ J o u r n a l P r e -p r o o f Different combinations of NPs and in situ gels were formulated and allowed a successful delivery of a variety of drugs, such as antimicrobial drugs (levofloxacin [131,134], vancomycin [139], fluconazole [140]), anti-glaucoma drugs (brimonidine [132], curcumin [135], dexamethasone [136], epinephrine [23], timolol [141]), anti-inflammatory drugs (keratolac [137], pranoprofen [138]) and 5-fluorouracil [133]. For example, chitosan NPs loaded in alginate/HPMC in situ gels increased precorneal retention time and limited the drainage via nasolacrimal conduct [131].…”

Biopharmaceutical Assessment of Dexamethasone Acetate-Based Hydrogels Combining Hydroxypropyl Cyclodextrins and Polysaccharides for Ocular Delivery

“…The corneas were removed and then mounted onto diffusion cells, with the epithelial layer exposed to the donor chamber. The latter was filled with 0.4 g of each ophthalmic formulation; whereas the receptor chamber was filled with 13 mL artificial tear fluid Balanced Salt Solution (BSS) According to Wen et al [ 20 ], the experiment was performed at 35 ± 1 °C in a thermostatic water bath with a moderate speed of rotation maintained for 24 h. Three corneas per formulation (n = 3) were used. A 1 mL sample was removed at predetermined time intervals (15 min, 30 min, 1 h, 2 h, and 4 h) and replaced with an equal volume of fresh medium to maintain the sink conditions.…”

Polymeric Nanoparticles for Drug Delivery: Recent Developments and Future Prospects

“…Some authors improved formulation efficacy by combining the use of drug-loaded micelles with specific media to enhance certain properties, mainly oriented to prolong the residence time of the formulation in the ocular globe. Wen et al [ 49 ] prepared a NP-loaded in situ gel as dexamethasone delivery system for ocular inflammation. The drug was contained in lecithin-based micelles while the in situ gel was obtained by a mixture of poloxamers (P188 and P407).…”