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Development and evaluation of anti-oxidant and anti-inflammatory drugs loaded lung surfactants

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Title Development and evaluation of anti-oxidant and anti-inflammatory drugs loaded lung surfactants
 
Creator SHAH, AR
BANERJEE, R
 
Subject RESPIRATORY-DISTRESS-SYNDROME
PULMONARY SURFACTANT
EXOGENOUS SURFACTANT
N-ACETYLCYSTEINE
MODEL
INJURY
INACTIVATION
ADSORPTION
MONOLAYERS
ASTHMA
 
Description Surface active liposomes containing, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) and dexamethasone disodium phosphate (DXP) were developed and evaluated for potential use as lung surfactant replacement. 1,2-dipalmitoyl-sn-glycerol-3-phosphatidylcholine (DPPC) + TPGS (1 : 0.25 w/w) surfactant system (S1) and binary mixture of DPPC with 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphoglycerol ammonium salt (DPPC : POPG 9 : 1 w/w) + TPGS (1 : 0.25 w/w) surfactant system (S2) containing incremental amount of DXP in the range of 1 : 0.1-1 : 1 w/w were evaluated. S1: DXP and S2: DXP (1 : 0.1 to 1 : 1 w/w) mixed films reached 1-2 mN m(-1) minimum surface tension (MST) indicating surfactant functions even on concomitant addition of TPGS and DXP. Liposomal S1: DXP (1 : 0.1 to 1 : 1 w/w) attained significantly lower surface tension on adsorption, 35-29 mN m(-1) in one second, in comparison to 46 mN m-1 attained by DPPC liposomes. Similarly, liposomes of S2: DXP (1 : 0.1-0.125 w/w) lowered surface tension on adsorption to 27-29 mN m(-1) in 1 second. Capillary surfactometer studies showed S1: DXP and S2: DXP (1 : 0.1-1 : 1 w/w) liposomes maintained >98% capillary patency. Rheological studies revealed that liposomal S2: DXP 1 : 0.1 and 1 : 0.125 w/w formulations (25 mg ml(-1)) exhibited shear thinning properties and had significantly lower shear viscosities of similar to 2.5 and 6.3 mPa s respectively at shear rate of 70 s(-1) in comparison to similar to 29 mPa s for Survanta (TM)(25 mg ml(-1)). S2: DXP 1 : 0.1 and 1 : 0.125 w/w liposomes were unilamellar with diameter of 200-250 and 250-350 nm respectively. Twin impinger drug deposition studies showed that on nebulization, S2: DXP 1 : 0.1 and 1 : 0.125 w/w liposomes system showed significantly higher deposition in the lower impingement chamber in comparison to that of free drug. Lipid peroxidation of Curosurf (TM) was reduced by 21-24% upon addition of S2: DXP liposomal formulation. The TPGS and DXP added DPPC : POPG liposomes may thus serve dual purposes of acting as a surfactant replacement and efficiently delivering antioxidant and anti-inflammatory drugs in inflammatory respiratory diseases.
 
Publisher ROYAL SOC CHEMISTRY
 
Date 2014-10-15T08:40:29Z
2014-10-15T08:40:29Z
2012
 
Type Article
 
Identifier SOFT MATTER, 8(47)11911-11922
http://dx.doi.org/10.1039/c2sm26776d
http://dspace.library.iitb.ac.in/jspui/handle/100/14707
 
Language en