Preparation and characterization of liposomes containing a lipophilic cisplatin derivative for clinical use

R. Perez-Soler, K. Francis, S. Al-Baker, F. Pilkiewicz, A. R. Khokhar

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Cis-bis-neodecanoato-trans-R,R-l,2 diaminocyclohexane platinum(II) (NDDP) is a lipophilic cisplatin derivative that has been formulated entrapped in multilamellar liposomes composed of dimyristoylphosphatidyl choline (DMPC) and dimyristoylphosphatidyl glycerol (DMPG). A phase I clinical study with liposome-entrapped NDDP (L-NDDP) administered i.v. every 4 weeks has been recently completed. L-NDDP was synthesized, manufactured, and reconstituted for clinical use in our laboratories. L-NDDP was prepared as a lyophilized powder containing the NDDP and the phospholipids (NDDP-lipid weight ratio 1: 15; DMPC-DMPG molar ratio 7: 3). The liposome suspension was obtained on the day of use just before administration to the patients by adding normal saline (final concentration 1 mg NDDP/ml) and shaking in a water-bath shaker at room temperature according to an established protocol. A total of 54 batches of lyophilized L-NDDP were prepared. Physical appearance, phospholipid content and integrity, and elemental platinum content were determined in all batches and found to be reproducible. All batches contained < 0.24ng/ml endotoxin. The amount of residual organic solvents was < 0.05 per cent. In all reconstituted doses, drug entrapment was > 90 per cent, and the proportion of liposomes measuring < 5 μm was < 20 per cent. Our results show that reproducible batches of liposomal preparations of new compounds can be prepared in the laboratory facilities of academic institutions, thus allowing for early clinical trials with novel therapeutic agents.

Original languageEnglish (US)
Pages (from-to)41-54
Number of pages14
JournalJournal of Microencapsulation
Volume11
Issue number1
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Bioengineering
  • Pharmaceutical Science
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Colloid and Surface Chemistry

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