Prevention of topical and ocular oxidative stress by positively charged submicron emulsion.
A positively charged submicron emulsion with zeta potential values ranging from 35 to 45 mV and mean droplet size around 150-250 nm has recently been developed and characterized. This formulation is based on three surface-active agents, an egg yolk phospholipid mixture, poloxamer 188, and stearylamine, a cationic lipid with a pKa of 10.6. The emulsion toxicity was evaluated in three animal studies. The results of the ocular tolerance study in the rabbit eye indicated that hourly administration of one droplet of the positively charged emulsion vehicle was well tolerated without any toxic or inflammatory response to the ocular surface during the five days of the study. No marked acute toxicity was observed when 0.6 mL of positively charged emulsion was injected intravenously to BALB/c mice. Furthermore, no difference was noted between this group of animals and the group injected with the marketed and clinically well accepted negatively charged Intralipid emulsion. These observations were further confirmed in a four week toxicity study following intravenous administration to rats of 1 mL/kg of the positively charged emulsion as compared to Intralipid. No toxic effect was noted in any of the various organs examined, whereas the results of the hematological and blood chemistry tests remained in the normal range for both emulsions, confirming the preliminary safety study findings. In addition, it was demonstrated by means of a non-invasive technique that alpha-tocopherol positively charged emulsions prevented oxidative damage in rat skin subjected to UVA irradiation. The intrinsic ability of positively charged emulsified oil droplets to protect against reactive oxygen species cannot be excluded, and could act synergistically with the antioxidant alpha-tocopherol itself. The effect of blank and piroxicam positively charged emulsions on rabbit eye following alkali burn was also evaluated. The blank emulsion showed a very rapid healing rate during the first three days with a breakdown in day 14. Complete re-epithelialization was observed in day 28. The same behavior (albeit less pronounced), was noted in piroxicam emulsion, although piroxicam is known to inhibit the epithelial healing process. It can therefore be deduced that the positively charged emulsion vehicle prevented piroxicam from interfering with the epithelial healing process due to the intrinsic free radical scavenger ability of the positively charged submicron emulsion previously demonstrated. Finally, the efficacy of this promising emulsion vehicle containing effective cosmetic ingredients in preventing skin damage and aging following oxidative stress is evaluated.
School of Pharmacy, Hebrew University of Jerusalem, Israel.
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Benita
D000588:Amines / Q000494:pharmacology; D000818:Animals; D004655:Emulsions / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009799:Ocular Physiological Phenomena / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010743:Phospholipids / Q000494:pharmacology; D020442:Poloxamer / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D012879:Skin Physiological Phenomena / Q000187:drug effects; D013501:Surface-Active Agents / Q000494:pharmacology*
D000588:Amines; D004655:Emulsions; D010743:Phospholipids; D013501:Surface-Active Agents; D020442:Poloxamer; C009317:stearylamine