New Advances in Nanocrystalline Apatite Colloids Intended for Cellular Drug Delivery

Abstract

Intracellular drug delivery using colloidal biomimetic calcium phosphate apatites as nanocarriers is a seducing concept. However, the colloid preparation to an industrial scale requires the use of easily handled raw materials as well as the possibility to tailor the nanoparticles size. In this work, the stabilization of the colloids was investigated with various biocompatible agents. Most interestingly, nanoscale colloids were obtained without the need for toxic and/or hazardous raw materials. Physico-chemical characteristics were investigated by chemical analyses, dynamic light scattering, FTIR/Raman spectroscopies, XRD, and electron microscopy. A particularly promising colloidal system associates biomimetic apatite stabilized with a natural phospholipid moiety (AEP(r), 2-aminoethylphosphoric acid). Complementary data described such colloids as apatite nanocrystals covered with surface Ca(2+)(AEP(r)(-))(2) complexes involving "supernumerary" Ca(2+) ions. The effects of the concentration in AEPr, synthesis temperature, duration of aging in solution, pH, and sonication were followed, showing that it is possible to modulate the mean size of the nanoparticles, typically in the range 30-100 nm. The perfect biocompatibility of such colloids allied to the possibility to prepare them from innocuous compounds shows great promise for intracellular drug delivery.

Nanodimensional and Nanocrystalline Calcium Orthophosphates

“…These examples emphasize that nanophase materials deserve more attention in improving orthopedic implant failure rates. However, to reduce surface energy, all nano-sized materials tend to agglomerate and, to avoid self-aggregation of calcium orthophosphate nano-sized particles [195][196][197][198], special precautions might be necessary [54,60,120,[199][200][201][202].…”

“…In contrast, nano-sized CDHA grown in the absence of organic additives are typical, rod-like particles with lengths of hundreds of nanometers and width of tens of nanometers [507]. Colloidal formulations are known as well [54,60,202]. Interestingly, but nano-sized apatites might perform crystalline to amorphous phase transformation when powders were aged for 5 months in 30% relative humidity [508].…”

Biomimetic Apatite-Based Functional Nanoparticles as Promising Newcomers in Nanomedicine: Overview of 10 Years of Initiatory Research

“…Figure 2c, reports the typical case of an AEP-stabilized apatite colloid prepared aged 16 hours at 100°C and for an AEP/ Ca initial molar ratio of 1. Table 1, reports in a tabulated format the size characteristics 3 of some of the colloidal nanoparticles obtained [40]. It may be noted that dimensions lower or around 100 nm were obtained for some of these suspensions, therefore opening perspectives in terms of nanoparticle/cells interaction in the field of nanomedicine where dimensions up to around 100 nm are often considered as optimal.…”

“…The methodology followed for the preparation of such colloids was summarized in figure 1 [41]. Insights on the stability of such colloids were sought, by following the 3 -Mode of the size distribution and polydispersity index [40]. .…”

Low-temperature synthesis of nanoparticle-assembled, transparent, and low-crystallized hydroxyapatite blocks

“…Therefore, HAp and its composites with polymers or metals have been widely used in orthopedic and dental applications. Other important applications of HAp are cell culture substrates to study cell behavior [3,4], supports for drug delivery [5], and cell scaffolds for tissue engineering [6][7][8].…”