A polymeric aqueous tacrolimus formulation for topical ocular delivery

Area of Science:

• Ophthalmology
• Pharmaceutics
• Nanotechnology

Background:

• Tacrolimus (TAC) is crucial for treating severe atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC).
• Existing TAC suspensions present challenges for ocular delivery due to their hydrophobic nature.
• Developing an aqueous formulation is essential for improved patient compliance and therapeutic efficacy.

Purpose of the Study:

• To formulate tacrolimus (TAC) into a stable, aqueous eye drop.
• To evaluate the ocular biodistribution of the novel TAC formulation in a rabbit model.
• To assess the potential of this formulation for treating AKC and VKC.

Main Methods:

• Tacrolimus (TAC) was encapsulated in a chitosan-based amphiphile (Molecular Envelope Technology - MET) using thin-film hydration.
• The resulting nanoparticle formulation (MET-TAC) was characterized for size, viscosity, osmolarity, and pH.
• Stability was assessed under refrigeration for one month.
• Ocular tissue and blood samples from rabbits were analyzed for TAC concentration using LC-MS/MS.

Main Results:

• A 200 nm nanoparticle formulation (MET-TAC) containing 0.1% TAC was successfully created, meeting ocular comfort parameters.
• The formulation demonstrated stability under refrigeration for one month.
• One hour post-application, significant TAC concentrations were found in rabbit cornea (4452 ± 2289 ng/g) and conjunctiva (516 ± 180 ng/g).

Conclusions:

• A stable, aqueous tacrolimus (TAC) eye drop formulation using Molecular Envelope Technology (MET) has been successfully developed.
• The MET-TAC formulation demonstrates effective delivery of TAC to key ocular surface tissues.
• This novel formulation holds promise for the topical treatment of atopic and vernal keratoconjunctivitis.