Type

Other / n/a

Authors

Sally-Ann Cryan
Noel G McElvaney
Clifford Taggart
Anthony J Hickey
Ciara Kelly
Danielle Padilla-Carlin
Aileen Gibbons

Subjects

Pharmacology

Topics
animal guinea pigs humans electric impedance liposomes secretory leukocyte peptidase inhibitor drug compounding pharmacy and pharmaceutical sciences drug stability animals disease models animal cell membrane permeability asthma enzyme linked immunosorbent assay disease models male cell line inhalation drug delivery systems administration respiratory mucosa anti asthmatic agents biological transport administration inhalation

The effect of liposome encapsulation on the pharmacokinetics of recombinant secretory leukocyte protease inhibitor (rSLPI) therapy after local delivery to a guinea pig asthma model. (2011)

Abstract PURPOSE: Inhaled recombinant Secretory Leukocyte Protease Inhibitor (rSLPI) has shown potential for treatment of inflammatory lung conditions. Rapid inactivation of rSLPI by cathepsin L (Cat L) and rapid clearance from the lungs have limited clinical efficacy. Encapsulation of rSLPI within 1,2-Dioleoyl-sn-Glycero-3-[Phospho-L-Serine]:Cholesterol liposomes (DOPS-rSLPI) protects rSLPI against Cat L inactivation in vitro. We aimed to determine the effect of liposomes on rSLPI pharmacokinetics and activity in vitro and after local delivery to the airways in vivo.METHODS: Transport of DOPS-rSLPI and free-rSLPI across a polarised air-liquid epithelial monolayer was measured. An asthma guinea pig model was administered either DOPS-rSLPI liposomes or free-rSLPI by intratracheal instillation.RESULTS: Apparent permeability (P(app)) of free-rSLPI was significantly higher at 4.9 x 10⁻⁶ cm/s than for DOPS-rSLPI, P(app) of 2.05 x 10⁻⁷ cm/s, confirmed by in vivo studies. Plasma rSLPI concentrations were highest in free-rSLPI-treated animals compared with those treated with DOPS-rSLPI; there also appeared to be a trend for higher intracellular rSLPI content in animals dosed with DOPS-rSLPI compared to free-rSLPI. Eosinophil influx was recorded as a measure of inflammation. Pre-dosing with either free-rSLPI or DOPS-rSLPI prevented inflammatory response to antigen challenge to levels comparable to control animals.CONCLUSION: Encapsulation of rSLPI in DOPS:Chol liposomes improves stability, reduces clearance and increases residence time in the lungs after local delivery.
Collections Ireland -> Royal College of Surgeons in Ireland -> School of Pharmacy
Ireland -> Royal College of Surgeons in Ireland -> School of Pharmacy Articles

Full list of authors on original publication

Sally-Ann Cryan, Noel G McElvaney, Clifford Taggart, Anthony J Hickey, Ciara Kelly, Danielle Padilla-Carlin, Aileen Gibbons

Experts in our system

1
Sally-Ann Cryan
Royal College of Surgeons in Ireland
Total Publications: 70
 
2
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
3
Clifford C Taggart
Royal College of Surgeons in Ireland
Total Publications: 54