Spray-congealed Solid Lipid Microparticles for the controlled Bisphosphonates release
Theaim of this work was to develop an innovative drug delivery system potentially useful for the local delivery of Bisphosphonates to bone tissue. We propose the use of Solid Lipid Microparticles (MPs),up to now mainly used for oral and topical drug delivery, as carrier for bisphosphonates due to the favourable biocompatibility and lower toxicity of the lipids compared with many polymers. Thedelivery platform consisted of a biomimetic α-tricalcium phosphate-gelatin cement (CPC) enriched with alendronate loaded MPs (MPs-AL) produced by the spray congealing technology. Alendronate directaddition to cement composition is limited since Alendronate is able to sequester calcium from calcium phosphates, thus preventing the setting of the cements. At variance, this approach permitted toload a relatively high amount of the drug on the CPC and allowed the controlled release of the highly water soluble alendronate. A Design of Experiment (DoE) was employed for the screening of theeffects of the formulation variables related to the presence of unloaded microparticle (MPs) on the cement most important mechanical properties. Then, MPs loaded with 10 % w/w of alendronate wereproduced using five different carriers (Stearic Acid, Stearilic Alcohol, Cutina HR, Tristearin and Precirol ATO5). All MPs-AL exhibited a spherical shape, encapsulation efficiency higher than 90% andprevalent particle size ranging from 100-150 micron. Solid state characterization (DSC, HSM and X-ray powder diffraction) demonstrated that encapsulation of alendronate into MPs did not alter itscrystal structure. MPs-AL addition to the cement provoked a modest lengthening of the setting times and of the hardening reaction leading to the complete transformation of α-tricalcium phosphate intocalcium-deficient hydroxyapatite, without significantly affect the cement mechanical properties. Moreover, the results of in vitro AL release study performed on cements enriched with MPs-AL showedthat the system allows a controlled release of the drug over time.