Reverse micelle-mediated synthesis of calcium phosphate nanocarriers for controlled release of bovine serum albumin

Abstract

Calcium phosphate (CaP) nanoparticle with calcium to phosphorus (Ca:P) molar ratio of 1.5:1 were synthesized using reverse micro emulsion. Ca(NO3)2.4H2O and H3PO4 were used as aqueous phase, cyclohexane as organic phase, and poly(oxyethylene)12 nonylphenol ether (NP-12) as surfactant. Depending on calcination temperature between 600 and 800 °C, CaP nanoparticle showed different phases calcium deficient hydroxyapatite (CDHA) and β-tricalcium phosphate (β-TCP), particle size between 48 and 69 nm, the BET specific average surface area between 73 m2/g and 57 m2/g. Bovine serum albumin (BSA) was used as a model protein to study loading and release behavior. Adsorptive property of BSA was investigated with the change in BET surface area of these nanoparticle and the pH of the suspension. At pH 7.5, maximum amount of BSA was adsorbed onto CaP nanoparticle. The release kinetics of BSA showed a gradual time dependent increase at pH 4.0 and 6.0 buffer solutions. However, the amount of released protein was significantly smaller at pH 7.2. BSA release rate also varied depending on the presence of different phases of CaPs in the system, β-TCP or CDHA. These results suggest that BSA protein release rate can be controlled by changing particle size, surface area and phase composition of CaP nanocarriers.

Modulating protein adsorption onto hydroxyapatite particles using different amino acid treatments

“…Therefore, BSA and lysozyme are negatively and positively charged, respectively, on their surface when dissolved in PBS buffered at pH 7.4. In addition to the surface charge of HA particles, the dissolution rate of materials also affects the protein adsorption [28]. The lower the crystallinity of HA, the higher would be its dissolution rate [23,32].…”

“…The mechanism of protein adsorption onto HA is initiated with the formation of a stern layer of anions, such as H 2 PO 3À 4 and OH 2 on the HA surface, followed closely by the dispersive electrical double layer around the surface [28]. Protein molecules are then adsorbed through the specific electrostatic interactions between charged groups of proteins and Ca 2þ .…”

“…Protein adsorption onto HA surfaces relies on three factors: (i) the inherent surface properties of materials, such as degree of crystallinity, surface area [21], surface energy and hydrophobicity [26]; (ii) physiological conditions including ionic strength [27], pH of working solutions [28]; and (iii) protein -material interactions such as specific binding at Ca 2þ and PO 3À 4 sites [29], non-specific binding through hydrogen bonding, electrostatic interactions, and so on. The mechanism of protein adsorption onto HA is initiated with the formation of a stern layer of anions, such as H 2 PO 3À 4 and OH 2 on the HA surface, followed closely by the dispersive electrical double layer around the surface [28].…”

Nanodimensional and Nanocrystalline Calcium Orthophosphates

“…Nanodimensional β-TCP powders with an average grain size of ~ 100 nm [173,524] and less [525] were prepared by wet precipitation methods, followed by calcining at elevated temperatures. Furthermore, a sol-gel technique [526], reverse micelle-mediated synthesis [527] and a polystyrene template method [528] are also applicable. In wet precipitation techniques, dialysis might be applied as a separation method [524].…”

In Vitro Release and Bioavailability of Silybin from Micelle-Templated Porous Calcium Phosphate Microparticles

“…Over the past decades, the application of porous calcium phosphate as carriers in drug delivery has attracted much attention due to significant advantages such as large specific surface area and high loading capacity for drug (3), protein (4,5), or DNA molecules (6,7). Among the application methods which include micelle-templated synthesis (8,9), emulsion process (10)(11)(12), and surfactant-assisted route (13,14), micelletemplated synthesis technique has been the most widely used. To date, polymeric micelle templates have been successfully applied to the fabrication of many porous calcium phosphate carriers.…”