Eyeworld

EW NEWS & OPINION 16 D rug delivery vehicles do matter. That's according to research that suggests that topical combination therapy of tobramycin and dexamethasone when applied via a new drug delivery system works better than standard topical administration. "The results of this study demonstrated that the tobramycin and dexamethasone combination therapy with a xanthan gum vehicle has an improved bactericidal effec- tiveness compared to the commer- cially available formulation, and maintains a similar anti-inflamma- tory effect while containing half the amount of steroid," according to a report by Charles L. Balzli, M.S., de- partment of microbiology, Univer- sity of Mississippi Medical Center, Jackson, and colleagues. The study was published online in October 2010 in Advances in Therapy. Earlier research has demon- strated the efficacy of a xanthan gum vehicle and supports the no- tion that it's no longer sufficient to develop new drugs in today's phar- maceutical world; superior ways to get them to the target areas of treat- ment are critical. In depth Mr. Balzli analyzed rabbit corneas in- trastromally injected with either a methicillin-sensitive S. aureus (MSSA) or methicillin-resistant S. au- reus (MRSA) strain. Eyes were then treated every hour from 10 to 15 hours with 0.1% dexamethasone (MaxiDex, Alcon, Fort Worth, Texas), 0.3% tobramycin (Tobrex, Alcon), 0.3% tobramycin with 0.1% dexamethasone (TobraDex, Alcon), or 0.3% to- bramycin with 0.05% dexametha- sone in a xanthan gum vehicle (TobraDex ST, Alcon). An untreated control group was also observed. There were six or more eyes infected in each group, which were subse- quently treated. "Eyes treated with ST demon- strated the most effective treatment against MSSA by significantly reduc- ing the CFUs [colony forming units] per cornea as compared with all treated groups," Dr. Balzli reported. Specifically, at 16 hours post-in- fection, untreated MSSA infected corneas had 6.73 +/–0.12 logs of bac- teria; dexamethasone-treated eyes had 6.73 +/–0.09 logs; tobramycin- only eyes had 5.88 +/–0.19 logs; to- bramycin and dexamethasone combination eyes had 5.69 +/–0.20 logs; and ST eyes had 3.70 +/–0.50 logs. In other words, dexamethasone eyes were no different in terms of bacterial load than controls. To- bramycin eyes and standard combi- nation eyes had significantly lower bacterial loads. ST eyes had the least bacteria of all groups. "Similar to the treatment find- ings for the MSSA strain, ST was the most effective formulation at reduc- ing the bacterial burden of MRSA in- fected corneas with significantly fewer bacteria than any of the other treated groups," Mr. Balzli reported. Untreated eyes had 7.02 +/–0.06 logs of bacteria at 16 hours post-in- fection; dexamethasone eyes had 6.79 +/–0.21 logs; tobramycin eyes had 5.61 +/–0.268 logs; standard combination eyes had 4.47 +/–0.57 logs; and ST eyes had 2.54 +/–0.40 logs. Dexamethasone eyes were not statistically different than control eyes in this regard. Further, although tobramycin and standard combina- tion eyes had reduced bacterial loads, ST was the best at reducing MRSA bacteria. Eyes were given SLE (slit lamp examination) scores from 0 (normal) to a theoretical 28 in terms of sever- ity of pathological changes. Scores were 8.66 +/–0.35 at 15 hours post-infection with MSSA for control eyes; 6.00 +/–0.28 for dex- amethasone eyes; 7.50 +/–0.54 for tobramycin eyes; 5.55 +/–0.47 for standard combination eyes; and 5.06 +/–0.81 for ST eyes. Scores were 11.42 +/–0.63 at 15 hours post-infection with MRSA for control eyes; 6.44 +/–0.58 for dex- amethasone eyes; 10.35 +/–1.51 for tobramycin eyes; 7.29 +/–0.70 for standard combination eyes; and 6.27 +/–0.58 for ST eyes. Clearly, eyes treated with ST had a significant decrease in SLE scores compared to controls, although these values were not markedly dif- ferent from the standard combina- tion eyes. It is meaningful, however, that the ST group contained half the amount of steroid as other steroid- containing groups. "The results show that the ST formulation, with an equivalent amount of tobramycin, was more ef- fective in killing bacteria than the commercially available formulations of tobramycin and dexamethasone, or tobramycin alone," Mr. Balzli re- ported. "The results also demon- strated that the ST formulation significantly reduced the inflamma- tion compared with untreated eyes, and reduced it to a level matching other steroid-treated groups, while containing half the amount of steroid. The CFU and SLE data demonstrate the abilities of the ST vehicle (xanthan gum technology) to amplify the penetration of avail- able antibiotic as well as the steroid. This improved delivery allows for the increased bactericidal capability as well as maintaining the effective- ness of the steroid with half the amount of drug." Mr. Balzli explained that the xanthan gum vehicle enhances con- tact time and drug delivery. "Xan- than gum is a water-soluble polysaccharide that has been found to have adherence properties that could make it useful in ocular med- ications," Mr. Balzli reported. Of course, active ingredients still matter. Mohan Rajan, M.D., medical director, Rajan Eye Care Hospital, Chennai, India, said that pred- nisolone, which is his steroid of choice, has better penetration and higher efficacy than dexamethasone. "Prednisolone has better pene- tration because it crosses the liquid barrier in the cornea better than dexamethasone," Dr. Rajan said. "That is also the reason why there are greater increases in IOP with prednisolone. We therefore monitor pressure very carefully after using prednisolone." EW Editors' note: Mr. Balzli has no finan- cial interests related to this study. The study was supported by funds from Alcon. Dr. Rajan has no financial inter- ests related to his comments. Contact information Balzli: cbalzli@umc.edu Rajan: rajaneye@vsnl.com March 2011 by Matt Young EyeWorld Contributing Editor Beyond the drugs: Study finds delivery vehicles are critical

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