Fabrication of Hybrid Nanocapsules by Calcium Phosphate Mineralization of Shell Cross-Linked Polymer Micelles and Nanocages

Abstract

Self-assembled shell cross-linked poly(acrylic acid-b-isoprene) (PAA78-b-PI97) micelles or cross-linked PAA nanocages in aqueous solution were used as templates for the preparation of novel polymer-inorganic nanocapsules. The hybrid nanostructures were typically 50-70 nm in diameter and consisted of spherical polymer nanoparticles or nanocages enclosed within a continuous 10-20 nm thick surface layer of amorphous calcium phosphate. Nucleation of calcium phosphate specifically in association with the polymer nanoparticles was facilitated by low supersaturation levels and by sequestration of Ca2+ ions within the carboxylate-rich PAA domains prior to addition of HPO4(2-). Modifications in ionic concentrations were used to control the calcium phosphate surface layer thickness and prepare mineralized cross-linked PAA-b-PI micelles with variable shell permeability. The permeability of beta-carotene into the hydrophobic PI core of mineralized shell cross-linked PAA-b-PI micelles was reduced by approximately 50 or 100% respectively for hybrid nanostructures enclosed within 10 or 20 nm thick calcium phosphate layers. Our results suggest that calcium phosphate-polymer cross-linked nanocapsules could have potential applications as pH-responsive biocompatible hybrid nanostructures for use in applications such as drug delivery, bioimaging, and therapeutics.

Polymer Micelle Formulations of Proteasome Inhibitor Carfilzomib for Improved Metabolic Stability and Anticancer Efficacy in Human Multiple Myeloma and Lung Cancer Cell Lines

“…In solution, calcium ions and phosphate ions react to form solid CP. Micelles or other nanoparticles can act as nucleation sites for this reaction, which results in the formation of a mineralized surface on the nanoparticle core (Perkin et al, 2005). CP formed away from the micelle particles can be removed easily, due to the insolubility of CP.…”

Biocomposites and hybrid biomaterials based on calcium orthophosphates

“…Various ACP-based biocomposites and hybrid formulations for dental applications have been developed, [508][509][510][511] and several ACP-based formulations have been investigated as potential biocomposites for bone grafting 419,[512][513][514] and drug delivery. 515 ACP/ PPF biocomposites were prepared by in situ precipitation, 513 while PHB/carbonated ACP and PHBHV/carbonated ACP biocomposites appeared to be well-suited as slowly biodegradable bone substitution materials.…”

Calcium orthophosphate-based biocomposites and hybrid biomaterials

“…Besides, several ACPbased formulations were investigated as potential biocomposites for bone grafting [349,[419][420][421]. Namely, ACP/PPF biocomposites were prepared by in situ precipitation [420], while PHB/carbonated ACP and PHBHV/ carbonated ACP biocomposites appeared to be well suited as slowly biodegradable bone substitution material [349].…”

“…Namely, ACP/PPF biocomposites were prepared by in situ precipitation [420], while PHB/carbonated ACP and PHBHV/ carbonated ACP biocomposites appeared to be well suited as slowly biodegradable bone substitution material [349]. Another example comprises hybrid nano-capsules of *50-70 nm in diameter which were fabricated by ACP mineralization of shell crosslinked polymer micelles and nanocages [421]. These nano-capsules consisted of a continuous ultrathin inorganic surface layer that infiltrated the outer crosslinked polymeric domains.…”

“…These nano-capsules consisted of a continuous ultrathin inorganic surface layer that infiltrated the outer crosslinked polymeric domains. They might be used as structurally robust, pH-responsive biocompatible hybrid nanostructures for drug delivery, bioimaging, and therapeutic applications [421].…”