Abstract
Purpose : To deliver loperamide (Lp) into mice brain using polysorbate 80 (PS80)-coated liposomes that inhibits P-glycoprotein (P-gp) efflux. Method : Lp loaded liposomes were prepared by reverse phase evaporation technique using lecithin (Lec) and cholesterol (Ch). The efficacy of PS80-coated Lp liposomes (PLs) in mice was evaluated using central analgesic models (Eddy’s hot plate method and tail immersion test) and peripheral analgesic model (acetic acid-induced writhing). Results : PLs showed maximum possible response (MPR) of 58.33 % at 60 min in Eddy’s hot plate study. In the tail immersion test, PLs showed MPR of 67.64 and 69.24 % at 60 and 90 min, respectively, relative to control group. This confirms the potential of PLs to deliver Lp to the brain by inhibiting P-gp efflux. Dose response study using tail flick method confirmed the minimum Lp dose (25 μg/kg, i.v) required to achieve central analgesic activity using PLs. Conclusion : PS80-coated Lp loaded liposomes (PLs) possess a good potential to inhibit P-gp efflux of Lp from brain, and also exhibit both central and peripheral analgesic activity. Keywords : Loperamide, Polysorbate 80, P-glycoprotein (P-gp), Analgesic activity
Highlights
Blood brain barrier (BBB) and cerebrospinal fluid barrier (CSFB) control the inflow of drug molecules into the brain
Tail immersion test reflected the same response with higher maximum possible response (MPR)% at 1 h for *Lp (73.21 %) followed by PS80 coated liposomal formulation (PLs) (67.64 %)
Our results have shown the potential analgesic effect of PLs in both Eddy’s hot plate and tail immersion tests
Summary
Blood brain barrier (BBB) and cerebrospinal fluid barrier (CSFB) control the inflow of drug molecules into the brain. Due to P-gp mediated efflux, Lp cannot enter into the brain thereby preventing its central analgesic activity It acts on gastrointestinal μ and δ opiate receptors and reduces gastrointestinal motility [6]. PS80 mimics the carrier as LDL particle and LDL receptor recognize it as its ligand, favoring its entry in to brain by endocytosis [10] Drugs such as tacrine, doxorubicin, hexapeptide and tubocurarine were targeted using PS80 surfactant [12]. Healthy Swiss albino mice weighing 20-25 g of either sex were maintained under controlled conditions of temperature at 23 ± 2 °C, humidity 55 - 60 % and a 12h light–dark cycle They were housed in sanitized polypropylene cages containing sterile paddy husk as bedding. Experimental protocols were reviewed and approved by the Institutional Animal Ethics Committee – Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Prist University (Registration No 292/CPCSEA/PHARMCEUT-11/06) and were performed in accordance with the National Institutes of Health guidelines for the care and use of laboratory animals(US) [29]
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