Liposome-collagen gel matrix: a novel sustained drug delivery system.

This report describes the properties of a novel sustained-release drug delivery system comprising liposomes sequestered in a collagen gel. Two peptide hormones, insulin and growth hormone encapsulated in vesicles sequestered within the matrix, are slowly released into the circulation from either an intramuscular or subcutaneous injection site. A maximum 3-5-d release for insulin or a 14-d growth hormone release was observed. Enhanced sequestration of liposomes with the collagen can be achieved by modifying the liposome surface with fibronectin. The liposome gel delivery system appears to offer several advantages over other liposome formulations or gel formulations constructed only with free drug.

Liposomes for protein delivery: selecting manufacture and development processes.

The use of liposomes as protein carriers has been investigated for a number of possible potential applications in pharmaceutical formulations. These are for sustained release to improve adjuvancy for vaccine development, protein absorption enhancement, and drug targeting carriers and as vehicles for administration of hydrophobic compounds. The majority of current liposomal protein formulations are still in various preclinical research stages, with relatively little known or reported human clinical findings to date. There are still pending challenges to creating commercially stable and bioactive protein formulations with lipids. In addition to lipid developmental issues, because the stability of proteins may be affected by many physical or chemical manipulations, the choice of manufacturing designs for liposomal incorporation becomes somewhat more complex. For this reason, solvent-free vesicle procedures should be the primary approach to the preparation of protein-based formulations. In this regard a variety of recently reported methods are discussed. The advantages or disadvantages of these procedures are compared to those of procedures involving solvents. Consideration to large-scale manufacturing and protein recovery issues is also given.

Encapsulation of indomethacin in liposomes provides protection against both gastric and intestinal ulceration when orally administered to rats.

Encapsulation of indomethacin into egg phosphatidylcholine (EPC) monophasic vesicles (MPV) or into stable plurilamellar vesicles (SPLV) before oral administration to rats substantially reduced or eliminated the gastric and intestinal ulceration normally associated with ingestion of this drug. Ulcers were assessed by the 4-hour single-dose gastric ulceration model and the 4- or 14-day repeated-dose intestinal ulceration model, using microscopic/planimetric quantitation. Oral dosages of up to 10 mg/kg of indomethacin in polyethylene glycol-400 resulted in substantial gastric ulceration, but not when given in methylcellulose suspension or as EPCMPV. Severe intestinal ulcers resulted following oral administration of indomethacin in either vehicle at daily 3-4-mg/kg doses, but did not result from EPCMPV formulations, whether dosed for 4 days or 14 days. Oral administration of pH-sensitive indomethacin liposomes constructed from cholesterol hemisuccinate resulted in loss of the protective action. Indomethacin-MPV showed both comparable bioactivity and comparable blood levels of the drug when contrasted with free drug in vehicles. Biodistribution studies demonstrated that when delivered from liposomes, drug and phospholipid are rapidly cleared through the stomach but then are differentially absorbed. Empty EPCMPV given by mouth also offered some protection against ulcers induced by systemic (subcutaneous) introduction of indomethacin, although better protective action was noted when the drug was first liposome-encapsulated and then given orally. The application of liposomes to the development of nonsteroidal antiinflammatory drugs that have minimal gastrointestinal side effects is discussed.

Novel liposome composition for a rapid colorimetric test for systemic lupus erythematosus.

This test for systemic lupus erythematosus utilizes a novel liposome composition entrapping the cation-responsive red dye Arsenazo III. In dilutions of normal sera the liposome membranes undergo a rearrangement when divalent cations are added, resulting in the release of the encapsulated dye and the rapid formation of a stable blue cation-dye complex. Microliter amounts of sera from patients with active lupus stabilize the liposome preparation such that the vesicles remain intact in the presence of the added divalent cations and thus maintain their red color for extended periods. The assay requires 1-min incubations in sera at room temperature and can be performed with standard microtiter plates, allowing the screening of large numbers of serum samples in a short time. Moreover, the unique absorption spectra of the complexed and uncomplexed dye allow for quantification of results.