Liposomes as carriers of different new lipophilic antitumour drugs: A preliminary report

F. Sampedro, J. Partika, P. Santalo, A. M. Molins-Pujol, J. Bonal, Roman Perez-Soler

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

We studied the liposome formulation characteristics of eight new lipophilic antitumour agents that have demonstrated a broad spectrum of antitumour activity in preclinical in vitro and in vivo screening models. Multilamellar vesicles were prepared by using standard evaporation/hydration methods. The drug to lipid weight ratio was 1: 15 in all cases. Different combinations of DMPC., DMPG and cholesterol were used. The quality of the liposomal formulations was evaluated by calculating the percentage drug bound to the liposome phase and assessing the morphology of the liposome phase by optic microscopy, to rule out the presence of drug crystals or drug/lipid microaggregates. Good liposomal preparations were obtained with hexamethylmelamine, penclomedine, mitindomide, and fazarabine. However, with taxol, batracylin, trimelamol, and diaziquone, the presence of crystals of free drug or microaggregates of lipid/drug complex was observed in all preparations, independently of lipid composition. In general, mixtures of DMPC DMPG at a molar ratio between 7: 3 and 9: 1, and the addition of 5 per cent cholesterol (w/w) gave the optimal results. In vitro cytotoxicity studies of free and liposomal drugs against L1210 cells showed changes in both directions after liposome entrapment, thus suggesting that liposome entrapment may alter drug cellular uptake or may result in chemical modifications of the entrapped drug. Because of the limited number of compounds studied we were unable to identify general chemical characteristics required for an enhanced liposome formation and drug entrapment.

Original languageEnglish (US)
Pages (from-to)309-318
Number of pages10
JournalJournal of Microencapsulation
Volume11
Issue number3
DOIs
StatePublished - 1994
Externally publishedYes

Fingerprint

Liposomes
Antineoplastic Agents
drugs
Lipids
Pharmaceutical Preparations
Cholesterol
entrapment
lipids
Dimyristoylphosphatidylcholine
batracylin
mitindomide
cholesterol
fazarabine
penclomedine
Crystals
diaziquone
Chemical modification
Cytotoxicity
Altretamine
Hydration

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Colloid and Surface Chemistry
  • Physical and Theoretical Chemistry
  • Bioengineering
  • Organic Chemistry
  • Chemistry (miscellaneous)
  • Chemical Engineering(all)
  • Pharmacology

Cite this

Liposomes as carriers of different new lipophilic antitumour drugs : A preliminary report. / Sampedro, F.; Partika, J.; Santalo, P.; Molins-Pujol, A. M.; Bonal, J.; Perez-Soler, Roman.

In: Journal of Microencapsulation, Vol. 11, No. 3, 1994, p. 309-318.

Research output: Contribution to journalArticle

Sampedro, F. ; Partika, J. ; Santalo, P. ; Molins-Pujol, A. M. ; Bonal, J. ; Perez-Soler, Roman. / Liposomes as carriers of different new lipophilic antitumour drugs : A preliminary report. In: Journal of Microencapsulation. 1994 ; Vol. 11, No. 3. pp. 309-318.
@article{6566b6fbaf194d789a980d1e1513364d,
title = "Liposomes as carriers of different new lipophilic antitumour drugs: A preliminary report",
abstract = "We studied the liposome formulation characteristics of eight new lipophilic antitumour agents that have demonstrated a broad spectrum of antitumour activity in preclinical in vitro and in vivo screening models. Multilamellar vesicles were prepared by using standard evaporation/hydration methods. The drug to lipid weight ratio was 1: 15 in all cases. Different combinations of DMPC., DMPG and cholesterol were used. The quality of the liposomal formulations was evaluated by calculating the percentage drug bound to the liposome phase and assessing the morphology of the liposome phase by optic microscopy, to rule out the presence of drug crystals or drug/lipid microaggregates. Good liposomal preparations were obtained with hexamethylmelamine, penclomedine, mitindomide, and fazarabine. However, with taxol, batracylin, trimelamol, and diaziquone, the presence of crystals of free drug or microaggregates of lipid/drug complex was observed in all preparations, independently of lipid composition. In general, mixtures of DMPC DMPG at a molar ratio between 7: 3 and 9: 1, and the addition of 5 per cent cholesterol (w/w) gave the optimal results. In vitro cytotoxicity studies of free and liposomal drugs against L1210 cells showed changes in both directions after liposome entrapment, thus suggesting that liposome entrapment may alter drug cellular uptake or may result in chemical modifications of the entrapped drug. Because of the limited number of compounds studied we were unable to identify general chemical characteristics required for an enhanced liposome formation and drug entrapment.",
author = "F. Sampedro and J. Partika and P. Santalo and Molins-Pujol, {A. M.} and J. Bonal and Roman Perez-Soler",
year = "1994",
doi = "10.3109/02652049409040460",
language = "English (US)",
volume = "11",
pages = "309--318",
journal = "Journal of Microencapsulation",
issn = "0265-2048",
publisher = "Informa Healthcare",
number = "3",

}

TY - JOUR

T1 - Liposomes as carriers of different new lipophilic antitumour drugs

T2 - A preliminary report

AU - Sampedro, F.

AU - Partika, J.

AU - Santalo, P.

AU - Molins-Pujol, A. M.

AU - Bonal, J.

AU - Perez-Soler, Roman

PY - 1994

Y1 - 1994

N2 - We studied the liposome formulation characteristics of eight new lipophilic antitumour agents that have demonstrated a broad spectrum of antitumour activity in preclinical in vitro and in vivo screening models. Multilamellar vesicles were prepared by using standard evaporation/hydration methods. The drug to lipid weight ratio was 1: 15 in all cases. Different combinations of DMPC., DMPG and cholesterol were used. The quality of the liposomal formulations was evaluated by calculating the percentage drug bound to the liposome phase and assessing the morphology of the liposome phase by optic microscopy, to rule out the presence of drug crystals or drug/lipid microaggregates. Good liposomal preparations were obtained with hexamethylmelamine, penclomedine, mitindomide, and fazarabine. However, with taxol, batracylin, trimelamol, and diaziquone, the presence of crystals of free drug or microaggregates of lipid/drug complex was observed in all preparations, independently of lipid composition. In general, mixtures of DMPC DMPG at a molar ratio between 7: 3 and 9: 1, and the addition of 5 per cent cholesterol (w/w) gave the optimal results. In vitro cytotoxicity studies of free and liposomal drugs against L1210 cells showed changes in both directions after liposome entrapment, thus suggesting that liposome entrapment may alter drug cellular uptake or may result in chemical modifications of the entrapped drug. Because of the limited number of compounds studied we were unable to identify general chemical characteristics required for an enhanced liposome formation and drug entrapment.

AB - We studied the liposome formulation characteristics of eight new lipophilic antitumour agents that have demonstrated a broad spectrum of antitumour activity in preclinical in vitro and in vivo screening models. Multilamellar vesicles were prepared by using standard evaporation/hydration methods. The drug to lipid weight ratio was 1: 15 in all cases. Different combinations of DMPC., DMPG and cholesterol were used. The quality of the liposomal formulations was evaluated by calculating the percentage drug bound to the liposome phase and assessing the morphology of the liposome phase by optic microscopy, to rule out the presence of drug crystals or drug/lipid microaggregates. Good liposomal preparations were obtained with hexamethylmelamine, penclomedine, mitindomide, and fazarabine. However, with taxol, batracylin, trimelamol, and diaziquone, the presence of crystals of free drug or microaggregates of lipid/drug complex was observed in all preparations, independently of lipid composition. In general, mixtures of DMPC DMPG at a molar ratio between 7: 3 and 9: 1, and the addition of 5 per cent cholesterol (w/w) gave the optimal results. In vitro cytotoxicity studies of free and liposomal drugs against L1210 cells showed changes in both directions after liposome entrapment, thus suggesting that liposome entrapment may alter drug cellular uptake or may result in chemical modifications of the entrapped drug. Because of the limited number of compounds studied we were unable to identify general chemical characteristics required for an enhanced liposome formation and drug entrapment.

UR - http://www.scopus.com/inward/record.url?scp=0028220719&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028220719&partnerID=8YFLogxK

U2 - 10.3109/02652049409040460

DO - 10.3109/02652049409040460

M3 - Article

C2 - 8064554

AN - SCOPUS:0028220719

VL - 11

SP - 309

EP - 318

JO - Journal of Microencapsulation

JF - Journal of Microencapsulation

SN - 0265-2048

IS - 3

ER -