Perspectives of Positively Charged Nanocrystals of Tedizolid Phosphate as a Topical Ocular Application in Rabbits

Abstract

The aim of this study was the successful utilization of the positively charged nanocrystals (NCs) of Tedizolid Phosphate (TZP) (0.1% w/v) for topical ocular applications. TZP belongs to the 1, 3-oxazolidine-2-one class of antibiotics and has therapeutic potential for the treatment of many drug-resistant bacterial infections, including eye infections caused by MRSA, penicillin-resistant Streptococcus pneumonia and vancomycin-resistant Enterococcus faecium. However, its therapeutic usage is restricted due to its poor aqueous solubility and limited ocular availability. It is a prodrug and gets converted to Tedizolid (TDZ) by phosphatases in vivo. The sterilized NC1 was subjected to antimicrobial testing on Gram-positive bacteria. Ocular irritation and pharmacokinetics were performed in rabbits. Around a 1.29 to 1.53-fold increase in antibacterial activity was noted for NC1 against the B. subtilis, S. pneumonia, S. aureus and MRSA (SA-6538) as compared to the TZP-pure. The NC1-AqS was “practically non-irritating” to rabbit eyes. There was around a 1.67- and 1.43 fold increase in t1/2 (h) and Cmax (ngmL−1) while there were 1.96-, 1.91-, 2.69- and 1.41-times increases in AUC0–24h,AUC0–∞,AUMC0–∞ and MRT0–∞, respectively, which were found by NC1 as compared to TZP-AqS in the ocular pharmacokinetic study. The clearance of TDZ was faster (11.43 mLh−1) from TZP-AqS as compared to NC1 (5.88 mLh−1). Relatively, an extended half-life (t1/2; 4.45 h) of TDZ and the prolonged ocular retention (MRT0–∞; 7.13 h) of NC1 was found, while a shorter half-life (t1/2; 2.66 h) of TDZ and MRT0–∞(t1/2; 5.05 h)was noted for TZP-AqS, respectively. Cationic TZP-NC1 could offer increased transcorneal permeation, which could mimic the improved ocular bioavailability of the drug in vivo. Conclusively, NC1 of TZP was identified as a promising substitute for the ocular delivery of TZP, with better performance as compared to its conventional AqS.

Mesoporous Silica Nanoparticles Coated with Carboxymethyl Chitosan for 5-Fluorouracil Ocular Delivery: Characterization, In Vitro and In Vivo Studies

“…The apparent permeability ( P app ) was estimated by the following equation: where C 0 is the initial drug concentration (2500 μg/mL) in the donor part [ 12 ].…”

“…Moreover, CMC was proposed as a material with good potential to prolong the corneal residence time of drugs, and CMC-coated nanoparticles were more efficient in enhancing the intraocular penetration of some drugs [ 8 ]. Based on these considerations, the hypothesis is that 5-FU loaded in AMSN and CMC-coated AMSN would increase the residence time of 5-FU at the precorneal and enhance the permeation of the drug inside the ocular structures [ 7 , 8 , 10 , 11 , 12 ].…”

Topical Application of Linezolid–Loaded Chitosan Nanoparticles for the Treatment of Eye Infections

“…This interaction helped in better penetration of CSNPs across the corneal and conjunctival layer, increased cellular uptake, and enhanced the bioavailability of LZ [ 16 , 61 , 62 ]. The smaller size of CSNPs could be another important reason for its enhanced transcorneal passage, which was also reported for improved ocular availability of hydrocortisone from the nanosuspension as compared to its micro–sized formulations [ 35 , 63 ]. Finally, the CSNPs was having prospective of improved ocular availability of LZ at small topical doses and reduced dosing frequency of LZ–CSNPs.…”

“…The obtained pellets of LZ–CSNPs were suspended in water, filtered through a 450 µ filtration unit, frozen at −70 °C, and freeze–dried (for 24 h at −50 °C and 0.02 mbar). The cryoprotectant (mannitol at 1%, w / v ) was mixed into the CSNPs–suspension before freeze–drying [ 35 ]. Finally, the freeze–dried products were stored at −20 °C for further experiments.…”

“…wt.) [ 3 , 16 , 35 , 47 , 50 ]. Successively,50 µL of AqH was taken out by a 29-gauge needle attached to a tuberculin syringe at predetermined time intervals.…”