| Abstract | We studied whether the therapeutic efficacy of the antifibrotic agent cis-4-hydroxy-L-proline (cHyp) in preventing bleomycin-induced pulmonary 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 retention was > 20% 1 wk after intratracheal instillation of 9 mumol phospholipid, 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 treated 1 and 2 wk later by single intratracheal instillation of test compounds. The control group received 0.3 ml saline (Bleo/sal). The treated groups received 9 mumol phospholipid in 0.3 ml of the following liposome 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 hydroxyproline/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 fibrosis did not show decreased fibrosis in the Bleo/lip-cHyp group, probably because of the focal nature of the fibrotic lesions. We conclude that cHyp encapsulated in liposomes prevents bleomycin-induced fibrosis by biochemical measurements. Delivery of antifibrotic agents to the lung in carrier vehicles promotes retention and may enhance their efficacy in treating bleomycin-induced pulmonary fibrosis. |
| Authors | G J Poiani, M Greco, J K Choe, J D Fox, D J Riley
(Affiliation: Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway.)
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| Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 150
Issue 6 Pt 1
Pg. 1623-7
(Dec 1994)
ISSN: 1073-449X UNITED STATES |
| PMID | 7524983
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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| Chemical References |
- Drug Carriers
- Liposomes
- Polyethylene Glycols
- Bleomycin
- Hydroxyproline
|
| Topics |
- Animals
- Bleomycin
- Drug Carriers
- Drug Evaluation, Preclinical
- Hydroxyproline
(administration & dosage, pharmacokinetics)
- Liposomes
- Lung
(drug effects, metabolism, pathology)
- Organ Size
(drug effects)
- Polyethylene Glycols
(administration & dosage, pharmacokinetics)
- Pulmonary Fibrosis
(chemically induced, metabolism, pathology, prevention & control)
- Rats
- Time Factors
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