In Situ Gelling Systems Using Pluronic F127 Enhance Corneal Permeability of Indomethacin Nanocrystals

Abstract

We previously designed an ophthalmic dispersion containing indomethacin nanocrystals (IMC-NCs), showing that multiple energy-dependent endocytoses led to the enhanced absorption of drugs from ocular dosage forms. In this study, we attempted to prepare Pluronic F-127 (PLF-127)-based in situ gel (ISG) incorporating IMC-NCs, and we investigated whether the instillation of the newly developed ISG incorporating IMC-NCs prolonged the precorneal resident time of the drug and improved ocular bioavailability. The IMC-NC-incorporating ISG was prepared using the bead-mill method and PLF-127, which yielded a mean particle size of 50–150 nm. The viscosity of the IMC-NC-incorporating ISG was higher at 37 °C than at 10 °C, and the diffusion and release of IMC-NCs in the IMC-NC-incorporating ISG were decreased by PLF-127 at 37 °C. In experiments using rabbits, the retention time of IMC levels in the lacrimal fluid was enhanced with PLF-127 in the IMC-NC-incorporating ISG, whereby the IMC-NC-incorporating ISG with 5% and 10% PLF-127 increased the transcorneal penetration of the IMCs. In contrast to the results with optimal PLF-127 (5% and 10%), excessive PLF-127 (15%) decreased the uptake of IMC-NCs after instillation. In conclusion, we found that IMC-NC-incorporating ISG with an optimal amount of PLF-127 (5–10%) resulted in higher IMC corneal permeation after instillation than that with excessive PLF-127, probably because of the balance between higher residence time and faster diffusion of IMC-NCs on the ocular surface. These findings provide significant information for developing ophthalmic nanomedicines.

Development of In-Situ Spray for Local Delivery of Antibacterial Drug for Hidradenitis Suppurativa: Investigation of Alternative Formulation

“…Pluronic F-127, as categorized in a family containing more than 30 ABA-type triblock copolymers [ 28 , 29 ] with the components of 70% polyoxyethylene units and 30% polyoxypropylene blocks, is found to be the most commonly used polymer in pharmaceuticals due to its varied nature, one of the most important characteristics being the ability to form a thermoreversible gel at the temperature close to body temperature [ 29 , 30 , 31 ]. It has been suggested that the effect of thermogelation is due to the dehydration at the critical micelle temperature of polyoxypropylene (PPO) blocks.…”

“…The increase in temperature would give a more significant result until the association of micelles occurs with each other at a specific temperature to form a gel. Moreover, another hypothesis has also been made suggesting that as the temperature increases, the modification of hydration spheres around the hydrophobic units could also induce the interactions along with the intramolecular hydrogen bonding effect [ 29 , 30 , 31 ]. From the results obtained, the average gelation temperature and gelation time decrease as the concentration of Pluronic F-127 increases, which leads to higher concentration of PPO responsible for the gelation effect.…”

“…Pluronic F-127 is considered a potential polymer because of its biocompatibility, which has been one of the most studied polymers in recent formulation development [ 34 ]. Although Pluronic F-127 could be used to prolong the residence time of the drug formulation [ 29 ], the maximum contact time, for instance in the human eye, was observed to last for just 1 h; in addition, one of the main drawbacks for Pluronic F-127 was its poor mechanical strength [ 30 ]. Therefore, to improve mechanical strength and adhesion time a combination of bioadhesive polymer with pluronic were used.…”

MPC Polymer Promotes Recovery from Dry Eye via Stabilization of the Ocular Surface

“…Atomic force microscopy (AFM) images were obtained via an A SPM-9700 (Shimadzu Corp., Kyoto, Japan), and AFM images were created by combining the phase and height images. The viscosity of MPCP was measured with an SV-1A at 10–40 °C (A&D Company, Limited, Tokyo, Japan) [ 14 ]. To confirm the wettability, defined as the tendency of one fluid to spread on or adhere to a solid surface, we performed contact angle measurements in 0.1% MPCP and 0.1% MPC-BMA aqueous solutions.…”

Prevention of Postprandial Hyperglycemia by Ophthalmic Nanoparticles Based on Protamine Zinc Insulin in the Rabbit

“…Moreover, we have found that particles approximately 150 nm in size result in increased ophthalmic absorption of a drug (indomethacin) via the multiple energy-dependent endocytosis system in the ocular surface [ 23 ]. Additionally, the combination of an in situ gelling system and drug NPs can achieve high ocular drug BA by enhancing the contact time of the NPs [ 23 , 24 , 25 ]. In addition, Yamamoto et al [ 26 ] reported that the combination of an INS solution, sodium glycocholate (NaGC), and polyacrylic acid (PAA) can maintain the INS level on the conjunctival sac after instillation and produce a significant increase in the contact time of the INS solution at the absorption site (conjunctival sac and nasal cavity), although they were unable to achieve practical utility.…”