Gj. Poiani et al., LIPOSOME ENCAPSULATION IMPROVES THE EFFECT ED ANTIFIBROTIC AGENT IN RAT LUNG FIBROSIS, American journal of respiratory and critical care medicine, 150(6), 1994, pp. 1623-1627
Citations number
31
Categorie Soggetti
Emergency Medicine & Critical Care","Respiratory System
We studied whether the therapeutic efficacy of the antifibrotic agent
cis-4-hydroxy-L-proline (cHyp) in preventing bleomycin-induced pulmona
ry fibrosis in rats is enhanced by intratracheal delivery in liposomes
. Dual-radiolabeled liposomes were used to study the distribution and
stability of liposomes after intratracheal instillation. Lung retentio
n was > 20% 1 wk after intratracheal instillation of 9 mu mol phosphol
ipid, and liposomes were intact as indicated by the ratio of the lipid
and aqueous-phase markers remaining unchanged. For the fibrosis study
, groups of rats were instilled with 1.2 U bleomycin (Bleo) and treate
d 1 and 2 wk later by single intratracheal instillation of test compou
nds. The control group received 0.3 ml saline (Bleo/sal). The treated
groups received 9 mu mol phospholipid in 0.3 ml of the following lipos
ome preparations: empty liposomes (Bleo/lip), liposomes and 100 mg/kg
of free unencapsulated cHyp (Bleo/lip/cHyp), and 100 mg/kg of liposome
-encapsulated cHyp (Bleo/lip-cHyp). At 3 wk, fibrosis (mg hydroxyproli
ne/g weight lung) by groups was as follows: control, 2.6 +/- 0.1 (SEM)
; Bleo/sal, 3.2 +/- 0.1, Bleo/lip, 3.2 +/- 0.1, and Bleo/lip/cHyp, 3.1
+/- 0.1, p < 0.05 compared with control; Bleo/lip-cHyp, 2.6 +/- 0.1,
p < 0.05 compared with Bleo/sal, n = 3 to 6. Histologic grading of fib
rosis did not show decreased fibrosis in the Bleo/lip-cHyp group, prob
ably because of the focal nature of the fibrotic lesions. We conclude
that cHyp encapsulated in liposomes prevents bleomycin-induced fibrosi
s by biochemical measurements. Delivery of antifibrotic agents to the
lung in carrier vehicles promotes retention and may enhance their effi
cacy in treating bleomycin-induced pulmonary fibrosis.