Calcium Phosphate and Calcium Phosphosilicate Mediated Drug Delivery and Imaging - Intracellular Delivery: Fundamentals and Applications - page 722

2.4 Significance of Surface Functionality in Calcium

Phosphate Delivery Systems

The reticuloendothelial system (RES) and the mononuclear phagocytic system
(MPS), identify and remove foreign particulates in the bloodstream and play a
major role in drug bioavailability (Allemann 1993 ). A factor that affects recogni-
tion of particles by the RES and macrophages of the MPS is the particle surface
chemistry. Certain surfaces are known to promote opsonization (a process that pro-
motes detection and removal by the RES or MPS). Therefore, particle surface
properties, more specifically, the hydrophobicity, hydrophilicity and charge of par-
ticles are usually modified to minimize opsonization. Hydrophobic nanoparticles
are easily coated with opsonins (molecules, such as antibodies, that promote phago-
cytosis) and hence more recognizable by the RES and the MPS. In contrast, hydro-
philic particles can resist the coating process to a greater extent and are more slowly
cleared from the blood stream (Allemann 1993 ; Kumar 2006 ).
Since suppression of opsonization increases the retention of particles in the
body, measures such as steric stabilization are employed to physically prevent
opsonin proteins from adsorbing to particle surfaces (Owens III 2005 ). PEG is
commonly used as a steric stabilization agent in an effort to improve dispersion of
particles and to prevent opsonization. PEGylation of particles is also commonly
utilized as a method to reduce renal clearance of smaller drug particles or mole-
cules. Therefore, properly designed synthetic schemes (relevant surface functional-
ities) can lead to improved bioavailability (due to longer circulation times) of
particles at the tumor site.

2.5 Targetability of Calcium Phosphate Nanoparticles

The two overarching schemes of drug delivery are passive and active targeting.
Passive targeting takes advantage of the enhanced permeation and retention (EPR)
effect present due to the leaky vasculature and poor drainage of tumors (Davis
1997 ; Torchilin 2000 ; Peer 2007 ). In contrast, active targeting employs cell specific
targets that are bioconjugated onto the surface of nanoparticles to exclusively target
the cells of interest. Targeted drug delivery is advantageous because it reduces
uptake of nanoparticles by healthy, non-cancerous cells, reduces the overall drug
dose necessary while increasing the dose at the target tissue and minimizing or
eliminating side effects and non-specific effects. For a more comprehensive review
of active and passive targeting, the reader is directed to publications by Davis,
Torchilin and Peer (Davis 1997 ; Torchilin 2000 ; Peer 2007 ).
Examples of targeting in calcium phosphate systems include studies by Li et al .
using lipid coated calcium phosphate (LCP) nanoparticles and Barth et al . using
calcium phosphosilicate nanoparticles (CPSNPs) (Li 2010 ; Barth 2010 ). The study
by Li et al . compares the gene silencing effect of untargeted LCP particles to