In vitro safety and permeation assessments of lidocaine loaded in dissolving microneedle patch for ocular administration

Abstract

The challenge in ocular drug delivery have brought much attention in pharmaceutical research. Efforts have been made to improve the low bioavailability causing by physiological limitations of ophthalmic drug administration. Topical lidocaine solution is a popular choice for ocular treatment, but less than 5% of topically applied dose reached to the target site. Lidocaine loaded in dissolving microneedle patch was considered a good alternative approach to treating eyes. The study aimed to investigate the cytotoxicity of the lidocaine loaded in dissolving microneedle administration against human corneal epithelial cells (HCECs) as well as ex vivo drug target localization with tissue penetration. In the case of cytotoxicity, HCECs cell viability was compared when given with different treatments; i.e., lidocaine solution, maltose solution and dissolved matrix of lidocaine microneedle patch. HCECs were analyzed for percent viability and stained for Dead/Life cell showed IC50 were 11.23, 22592.96 and 9.50 mg/mL, respectively. In Dead/Life cell evaluation using calcein AM and propidium iodide, live cells showed green fluorescent and dead cell showed red fluorescent. Form modified-franz diffusion method used to study permeation partition coefficient of lidocaine solution and lidocaine microneedle patch. The drug retained on the sclera was also determined. Sclera permeation tests were ensured the non-toxic or neglectable amount of drug getting permeated out of porcine sclera. In the case of lidocaine solution, we found that more than 80 Percent or 7.19 mg/cm2 of the drug retained on the sclera with undetectable amount of lidocaine permeated through the membrane. The permeation coefficient of lidocaine hydrochloride solution could not be determined because of drug absent in the receptor chamber. However, lidocaine loaded in dissolving microneedle patch showed drug was adsorbed in the range 2.68 – 3.36 mg/cm2 and localized in sclera tissue in the range 4.18 – 4.51 mg/cm2. Another interesting observation is that the amount of drug adsorbed on the surface of sclera tissue was independent with the thickness of porcine sclera. In the conclusion, lidocaine loaded in dissolving microneedle was shown to be safe and exhibited excellent permeation property or targeted drug delivery.