Encapsulation and release of a hydrophobic drug from hydroxyapatite coated liposomes.

Hydroxyapatite (HA) coated liposomes (HACL) have been successfully manufactured and filled with a model hydrophobic (lipophilic) drug, indomethacin (IMC). These HACL particles have been characterized in terms of particle size and zeta-potential. The liposomes are formed from 1,2-dimyristoyl-sn-glycero-3-phosphate (DMPA) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Altering their relative proportions caused the zeta-potential to change from -38.8 to -67.0 mV, with a concomitant change in phase transition temperature from 36.4 to 53.3 degrees C. These changes also affect the drug loading efficiency. The release profiles of IMC have been measured. HA coating of the liposome reduces the release rate of IMC over uncoated liposomes. Under the present experimental conditions 70% of the drug is released after approximately 5h from the liposome, but coating with HA changes this time to over 20 h. Perhaps most importantly, it has been observed that for uncoated liposomes, IMC is released at a greater rate at pH=7.4 than at pH=4. However, coating with HA reduced the rate at pH=7.4 compared to pH=4. This behaviour arises because IMC is more soluble under basic conditions, but HA is more soluble under acidic conditions. This behaviour shows that it is now possible to have environmental control over the release of drugs from HA-coated liposomes.