title: In situ DOX-calcium phosphate mineralized CPT-amphiphilic gelatin nanoparticle for intracellular controlled sequential release of multiple drugs.
abstract: A co-delivery strategy has been developed to achieve the synergistic effect of a hydrophobic drug (camptothecin, CPT) and a hydrophilic drug (doxorubicin, DOX) by utilizing the unique structure of amphiphilic gelatin/camptothecin @calcium phosphate-doxorubicin (AG/CPT@CaP-DOX) nanoparticles as a carriers in order to replace double emulsions while preserving the advantages of inorganic materials. The hydrophobic agent (CPT) was encapsulated via emulsion with an amphiphilic gelatin core, and subsequently mineralized by CaP-hydrophilic drug (DOX) through precipitation to form a CaP shell on the CPT-AG amphiphilic gelatin core so that drug molecules with different characteristics (i.e. hydrophobic and hydrophilic) can be encapsulated in different regions to avoid their interaction. The existence of the CaP shell can protect the DOX against free release and cause an increased transfer of DOX across membranes, overcoming multidrug resistance. Release studies from core-shell carriers showed the possibility of achieving sequential release of more than one type of drug by controlling the pH-sensitive CaP shell and degradable AG core. The highly pH-responsive behavior of the carrier can modulate the dual-drug-release of DOX/CPT, specifically in acidic intracellular pH environments. The AG/CPT@CaP-DOX nanoparticles also exhibited higher drug efficiencies against MCF-7/ADR cells than MCF-7 cells, thanks to a synergistic cell cycle arrest/apoptosis-inducing effect between CPT and DOX. As such, this core-shell system can serve as a general platform for the localized, controlled, sequential delivery of multiple drugs to treat several diseases, especially for multidrug-resistant cancer cells.
authors.affiliation: Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Li
authors.affiliation: Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Su
authors.affiliation: Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan. Electronic address: sanyuanchen@mail.nctu.edu.tw.
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Chen
mesh_terms: D002130:Calcium Phosphates / Q000737:chemistry*; D002166:Camptothecin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000494:pharmacology*; D065546:Drug Liberation; D005434:Flow Cytometry; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D042541:Intracellular Space / Q000737:chemistry*; D008027:Light; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D012542:Scattering, Radiation; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D013501:Surface-Active Agents; D004317:Doxorubicin; D005780:Gelatin; C020243:calcium phosphate; D002166:Camptothecin
keywords: Amphiphilic gelatin; Calcium phosphate; Drug release; Multidrug resistance; pH-sensitivity