The Acute and Subchronic Toxicity Profile of the Self- Nanoemulsifying Drug Delivery System (SNEDDS) Preparation From Propolis on Wistar Rats (Rattus Norvegicus)

Abstract

Background : Propolis is known for a number of pharmacological effects, such as antioxidant, immunomodulatory, and anti-inflammatory. One of the drug formulation technologies is the Self Nano Emulsifying Drug Delivery System (SNEDDS), which has the potential to overcome drug solubility and absorption. However, the nano-size drug particle may potentially cause toxicity. Aim : To determine the acute and subchronic toxicity profile of the SNEDDS (Self Nano Emulsifying Drug Delivery System) propolis extract on Wistar rats (Rattus norvegicus). Method : The SNEDDS propolis was tested for toxicity with acute OECD 425 and subchronic toxicity OECD 408 method using test animals. Acute test were carried out limit test on 2000 mg/kgBW and main test based on regression factor 3.2 (175; 550 and 2000 mg/kgBW). Treatment group for subchronic given graduated dose from 250;500 and 1000 mg/kgBW. Observations were carried out intensive for 14 days in acute, while in the subchronic for 90 days and follow-up observations for 28 days for the satellite group. Observation were made to clinical toxicity symptoms, body weight, hematology and clinical biochemistry examinations and macropathology. Result : The LD50 value of SNEDDS propolis was greater than 2000 mg/kgBW after acute toxicity test and classified to low toxicity category 4. The symptoms experienced by the test animals were lethargy, locomotor decrease, increase in defecation and symptoms refers to respiratory illness, but there were no died case until the end of the study both in acute and subchronic test. The body weight observation shows increase compared to the day 0. Meanwhile in visual observation of organ not indicates to toxicity. Conclusion : SNEDDS propolis did not cause toxicity both in acute or subchronic test.