Pharmaceutical Manufacturing Handbook: Production and

1230 CYCLODEXTRIN-BASED NANOMATERIALS IN PHARMACEUTICAL FIELD
The antiviral agent saguinavir was complexed to HP - β - CD to increase saquinavir
loading into polyalkylcyanoacrylate nanoparticles by providing a soluble drug reservoir
in the polymerization medium that is the basis of nanoparticle formation [29] .
A dynamic equilibrium was observed between the complex, dissociated species of
the complex, and the forming polymeric nanoparticle. During nanoparticle formation,
free drug was believed to be progressively incorporated into a polymer network,
driven by the drug partition coeffi cient between the polymer and polymerization
medium. Simultaneous direct entrapment of some CD – drug complex was also suspected
[28 – 30] .
Incorporation of the steroidal drugs hydrocortisone and progesterone in complex
with β - CD and HP - β - CD reduced the particle size for solid lipid nanoparticles
(SLNs) below 100 nm. Steroids were demonstrated to be dispersed in the amorphous
state. Compexation to CDs resulted in higher drug - loading properties for the
more hydrophobic drug hydrocortisone and lower in vitro release for both drugs
when they are complexed to CDs rather than their free form [31] .
The in vivo behavior of nanoparticles obtained from drug – CD complexes was
also evaluated. HP - β - CD addition in the polymerization medium of polyethylcyanoacrylate
(PECA) nanospheres improved the subcutaneous absorption of metoclopramide
in rats. PECA nanospheres with HP - β - CD provided the highest drug
concentration and enhanced drug absorption compared with those with dextran or
with drug solution. However, in addition to drug absorption from subcutaneous
sites, HP - β - CD also enhanced the drug elimination by enhancing the drug absorption
to reticuloendothelial tissues [32] .
Progesterone complexed to HP - β - CD or DM - β - CD was loaded into bovine
serum albumin (BSA) nanospheres. Dissolution rates of progesterone were signifi -
cantly enhanced by complexation to CDs with respect to free drug. Nanospheres of
100 nm loaded with drug – CD complexes provided a pH - dependent release profi le
and good stability in an aqueous neutral environment [33] .
In another approach, CD properties of complexation were combined with those
of chitosan. Complexation with CD was believed to permit solubilization as well as
protection for labile drugs while entrapment in the chitosan network was expected
to facilitate absorption. Chitosan nanoparticles, including complexes of HP - β - CD
with the hydrophobic model drugs triclosan and furosemide, were prepared by ionic
cross - linking of chitosan with sodium tripolyphosphate (TPP) in the presence of
CDs. Nanoparticles were then prepared by ionotropic gelation using the obtained
drug – HP -β - CD inclusion complexes and chitosan. Cyclodextrin and TPP concentration
largely affected particle size but the zeta potential remained unchanged with
different parameters. On the other hand, drug entrapment increased up to 4 and 10
times by triclosan and furosemide, respectively. The release profi le of nanoparticles
indicated an initial burst release followed by a delayed release profi le lasting up to
4 h [34] .
Recently a CD – insulin complex was encapsulated in polymethacrylic acid – chitosan
– polyether[polyethylene glycol (PEG) – propylene glycol] copolymer PMCP
nanoparticles from the free - radical polymerization of methacrylic acid in the presence
of chitosan and polyether in a medium free of solvents or surfactants. Particles
had a size distribution of 500 – 800 nm. The HP - ß - CD inclusion complex with insulin
was encapsulated into the nanoparticles, resulting in a pH - dependent release profi le
as seen in Figure 2 . The biological activity of insulin was demonstrated with enzyme -