Overcoming glucocorticoid resistances and improving antitumor therapies: lipid and polymers carriers.

Abstract

PURPOSE:

To improve chemotherapy protocols of lymphoid malignancies, by using polymeric and lipid microparticles as controlled delivery systems of dexamethasone, part of all combined chemotherapy protocols for its strong-inducing effect on malignant lymphoblasts.

METHODS:

Polymeric microparticles were prepared by the oil-in-water-emulsion cosolvent evaporation method, andlipid microparticles by spray drying. Their cytotoxic effects on GC-sensitive PC12 cells and GC-resistant PC3 cells were characterized by cell proliferation and apoptosis assays.

RESULTS:

Both elaboration methods rendered optimal-sized microparticles for parenteral administration with high drug loading. In vitro assays showed sustained dexamethasone release from polymeric microparticles over a month, whereas 100% dexamethasone release from lipid microparticles was achieved within 24 h. Similar PC12 cell death to that obtained with dexamethasone solution administered every 48 h was achieved with dexamethasone polymeric microparticles in 26-days assays. Dexamethasone solution and loaded polymeric microparticles induced apoptosis around 15.8 and 19.9%, respectively, after 2 days of incubation. Lipid microparticles increased further apoptosis induction in PC12 cells and, unlike dexamethasone solution and polymeric microparticles, showed antiproliferative effects on PC3 cells.

CONCLUSIONS:

Dexamethasone polymeric microparticles constitute an alternative to current dexamethasone administration systems in combined chemotherapy, whereas dexamethasone lipid microparticles represent a potential tool to revert glucocorticoid resistance.

• Authors: C Martín-Sabroso, A J Moreno-Ortega, J Aparicio-Blanco, A I Fraguas-Sánchez, M F Cano-Abad, A I Torres-Suárez
• Journal: Pharmaceutical research (Pharm Res) Vol. 32 Issue 3 Pg. 968-85 (Mar 2015) ISSN: 1573-904X [Electronic] United States
• PMID: 25213776 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Lipids
• Polymers
• Dexamethasone

Topics

• Adrenal Gland Neoplasms (pathology)
• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Chemistry, Pharmaceutical
• Dexamethasone (chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Drug Carriers
• Drug Resistance, Neoplasm
• Kinetics
• Lipids (chemistry)
• PC12 Cells
• Particle Size
• Pheochromocytoma (pathology)
• Polymers (chemistry)
• Rats
• Solubility
• Technology, Pharmaceutical (methods)