Biodegradable Polymeric Assemblies for Biomedical Materials - Polymers in Nanomedicine - page 80

then poured into a larger amount of water to give a w/o/w emulsion. After evapora-
tion, centrifugation, washing and drying, the MSs containing hydrophilic drugs in
the internal aqueous phase would be obtained.
Biodegradable aliphatic polyesters MSs have been used for drug delivery
devices that release drug in sustained manner. The most famous product is Lupron
Depot, which consists of 20- m m MSs of PLGA (LA:GA

¼

75:25) prepared by a
w/o/w emulsion method and releases luteinizing hormone-releasing hormone
(LH-RH) superagonist (leuprorelin acetate) for endocrine diseases,

including

prostate cancer [ 176 - 179 ].
We could prepare MSs having reactive surfaces using poly(DP- co -LA)s, i.e.,
poly[(Glc-Lys)- co -LA] and poly[(Glc-Asp)- co -LA], having reactive amino or
carboxylic acid groups [ 180 ]. In an o/w emulsion system, the hydrophilic amino
and carboxylic acid groups of the polymers were condensed at the interface of
aqueous and organic phases to give surface functionality to the MSs. We then reported
the introduction of saccharide (galactose) residues on the MSs to give cell-specific
recognition ability using the reactive functional groups on the surfaces [ 180 ].
In o/w and w/o/w emulsion methods, amphiphilic molecules or polymers,
typically poly(vinyl alcohol) (PVA), are usually added to the aqueous phase as
emulsion stabilizers (surfactants), to stabilize aqueous and oil phase droplets.
To obtain NSs having smaller (nanometer order) diameters compared with MSs,
the conditions of stirring and sonication, and the addition of surfactants are very
important. Amphiphilic biodegradable polymers can be used as biodegradable
surfactants instead of nonbiodegradable PVA. We reported the use of PDP-
b -PLAs having hydrophilic PDP segments as biodegradable surfactants to obtain
NSs and MSs with functionalized surfaces [ 181 , 182 ]. Using PDP- b -PLAs having
hydrophilic amino or carboxylic acid groups (i.e., poly(Glc-Lys)- b -PLA and poly
(Glc-Asp)- b -PLA) as biodegradable surfactants, NSs of aliphatic polyester could
be obtained without PVA by an o/w emulsion method [ 181 ]. In addition, fine and
uniform distribution of internal aqueous phase containing water-soluble drugs
could be achieved by the addition of the PDP- b -PLAs as biodegradable surfactants
to the w/o/w emulsion. The fine and uniform distribution of aqueous phase
containing bovine serum albumin (BSA) as model protein drug led to sustained
release of the protein from the obtained MSs (Fig. 8 )[ 182 ]. We also reported the
use of amphiphilic PLA-grafted polysaccharides to prepare MSs containing hydro-
philic drugs. We prepared MSs containing fluorescein isothiocyanate(FITC)-
labeled BSA as a model drug using Dex- g -PLLA, and investigated the distribution
of FITC-BSA in the MSs and its release behavior. The efficient entrapment and
uniform distribution of FITC-BSA in the MSs compared with PLLA could be
achieved [ 183 ]. In addition, the application of MSs prepared from block
copolymers of PEG and PLA for a vaccine delivery system has been described in
a short review [ 184 ].
The addition of amphiphilic polymer in o/w or w/o/w emulsion systems is also
useful to give surface functionality to MSs and NSs. Liang et al. reported prepara-
tion of NSs from poly( g -glutamic acid)- b -PLA, immobilizing galactose residues on
the surface by an o/w emulsion method, and in vivo specific delivery of aniticancer