mobic and Endophthalmitis

Postcataract endophthalmitis treatment through eye drops is of low corneal bioavailability and short residence time. The dominant NSAIDs therapy also suffers from severe ocular irritancy and low patients compliance. This study dispersed bovine serum albumin (BSA) coated meloxicam (MX) nanocrystals encapsulating nanoaggregates (BSA-MX-NA) in contact lenses to reduce drug ocular irritancy and increased drug release duration. The BSA-MX-NA (∼100 nm) were prepared using acid-base neutralization in aqueous solutions and were dispersed in poly(hydroxylethyl methacrylate) gels, which are common contact lens materials. Drug release studies showed that the gels released the drug for about 5 days. The proposed drug transport mechanism is a diffusion process which can be described by the Ritger-Peppas model with the diffusional exponent n of 0.4768. The drug release can be affected by the gel thickness and the cross-linking degree. A 400 micro thick gels with 100 μL cross-linker TEGDMA leads to an adequate meloxicam release for therapeutic application. The ocular irritation studies showed that BSA-MX-NA loaded p-HEMA gels are significantly less irritating to the ocular tissues as compared to marketed MX solutions. The developed contact lenses loaded with BSA-MX-NA could be very useful for extended delivery in postcataract endophthalmitis treatment.

Topics: Administration, Ophthalmic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cataract Extraction; Cattle; Contact Lenses; Cornea; Delayed-Action Preparations; Drug Compounding; Drug Delivery Systems; Endophthalmitis; Female; Gels; Male; Meloxicam; Nanostructures; Polyhydroxyethyl Methacrylate; Postoperative Complications; Rabbits; Serum Albumin, Bovine; Solubility; Surface Properties; Thiazines; Thiazoles; Tissue Distribution

To determine the efficacy of meloxicam ophthalmic formulation on COX-2 activity and expression, inflammation-related cytokines expression and inflammation in an ocular inflammation model.. Ocular inflammation was induced in New Zealand rabbits by topical application of croton oil (3%) for 3 h. An ophthalmic solution of 0.03% meloxicam, 0.1% sodium diclofenac or vehicle (Sophisen) was administered every 4 h. Conjunctiva, cornea, aqueous humour and vitreous humour were collected.. In irritated eyes, 72 h of meloxicam treatment downregulated COX-2 expression and activity (mRNA by RT-PCR and PGE2 levels by ELISA, respectively) in a time-dependent manner and reduced inflammation. Meanwhile, diclofenac failed to reduce COX-2 mRNA or PGE2 to basal levels after 7 days of treatment. Meloxicam treatment downregulated IL-6 and IFN-gamma expression in the conjunctiva and IL-1beta and TNF-alpha expression in the cornea. Diclofenac failed to modify these cytokines in both tissues. Meloxicam treatment increased the expression of IL-6 in conjunctiva, and IL-10 in cornea, while diclofenac had no effect on these cytokines.. Meloxicam treatment was more efficient than diclofenac in downregulating the expression and activity of COX-2, reducing inflammation, and modifying the inflammatory-related cytokines.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aqueous Humor; Cornea; Croton Oil; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cytokines; Dinoprostone; Disease Models, Animal; Down-Regulation; Drug Evaluation, Preclinical; Endophthalmitis; Male; Meloxicam; Ophthalmic Solutions; Rabbits; RNA, Messenger; Thiazines; Thiazoles