Synthesis and Characterization of PLGA Shell Microcapsules Containing Aqueous Cores Prepared by Internal Phase Separation
AAPS PharmSciTech
Synthesis and Characterization of PLGA Shell Microcapsules Containing Aqueous Cores Prepared by Internal Phase Separation
Samer R. Abulateefeh ) 0
Alaaldin M. Alkilany 0
0 Department of Pharmaceutics and Pharmaceutical Technology, Fac- ulty of Pharmacy, The University of Jordan , Amman, 11942 , Jordan
The preparation of microcapsules consisting of poly(D,L-lactide-co-glycolide) (PLGA) polymer shell and aqueous core is a clear challenge and hence has been rarely addressed in literature. Herein, aqueous core-PLGA shell microcapsules have been prepared by internal phase separation from acetonewater in oil emulsion. The resulting microcapsules exhibited mean particle size of 1.1±0.39 μm (PDI=0.35) with spherical surface morphology and internal poly-nuclear core morphology as indicated by scanning electron microscopy (SEM). The incorporation of water molecules into PLGA microcapsules was confirmed by differential scanning calorimetry (DSC). Aqueous core-PLGA shell microcapsules and the corresponding conventional PLGA microspheres were prepared and loaded with risedronate sodium as a model drug. Interestingly, aqueous core-PLGA shell microcapsules illustrated 2.5-fold increase in drug encapsulation in comparison to the classical PLGA microspheres (i.e., 31.6 vs. 12.7%), while exhibiting sustained release behavior following diffusion-controlled Higuchi model. The reported method could be extrapolated to encapsulate other water soluble drugs and hydrophilic macromolecules into PLGA microcapsules, which should overcome various drawbacks correlated with conventional PLGA microspheres in terms of drug loading and release.
internal phase separation; microcapsules; microspheres; poly(D; L-lactide-co-glycolide); risedronate sodium
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Poly(D,L-lactide-co-glycolide) (PLGA) is a polyester
random copolymer consisting of two monomers: lactic acid and
glycolic acid. PLGA is a FDA-approved polymer for human
use owing to its biocompatibility and biodegradability (1).
Therefore, PLGA has been extensively used in biomedical
and drug delivery applications (2). Moreover, this polymer is
one of the most polymers used successfully in the preparation
of microparticles and nanoparticles.
According to the internal structure, PLGA microparticles
are classified into two types: microspheres and microcapsules
(Fig. 1) (3). Microspheres are monolithic particles
characterized with an internal continuous matrix. On the other hand,
microcapsules are vesicular particles consist of a polymer shell
surrounding a single core (mono-nuclear) or multi-cores
(poly-nuclear) filled with oil or water. PLGA microspheres
and, to less extent, oily core microcapsules are the most
commonly prepared types due to their ease of preparation (4).
Unfortunately, both of these types are mainly appropriate for
encapsulating hydrophobic drugs; however, they suffer from
low encapsulation efficiency of water-soluble drugs, peptides,
and proteins (5).
In fact, fabrication of aqueous core-PLGA shell
microcapsules is a clear challenge. Therefore, very limited studies
have addressed this point in the literature (6,7). These studies
came mainly in an attempt to overcome drawbacks related to
the conventional w1/o/w2 double emulsion method (6–10).
They involved in situ formation of w1/o/w2 double emulsion
from a single o/w emulsion via spontaneous self-emulsification
by using either an appropriate emulsifier such as sodium
dioctyl sulfosuccinate (Aerosol OT or AOT) (6) or a
copolymer as poly(D,L-lactide)-b-poly(2-dimethylaminoethyl
methacylate)(PLA-b-PDMAEMA) (7).
Internal phase separation is another promising approach
proposed firstly by the Vincent group to prepare oil core-shell
microcapsules (4,11–13). This approach was then utilized to
prepare aqueous core microcapsules using three polymers:
poly(tetrahydorfuran), poly(methyl methacrylate), and
poly(isobutyl methacrylate) (9). This method involves
onestep formation of acetone-water in oil emulsion. The internal
phase contains the polymer-forming shell dissolved in a
mixture of a volatile good solvent (acetone) and a non-volatile bad
solvent (water). After emulsification in oil, gradual
evaporation of acetone leads to a decrease in polymer solubility and
hence polymer precipitation (coacervation) (11). At optimum
balance between the interfacial tensions of different phases
(14), polymer migrates to the interface forming a shell
surrounding aqueous compartment.
Herein, we employed this method, for the first time, to
prepare aqueous core-PLGA shell microcapsules. These
Fig. 1. A schematic presentation of internal morphology of a
microsphere, b microcapsule with poly-nuclear cores, and c microcapsule
with mono-nuclear core
particles were loaded with risedronate sodium as a model
drug. Risedronate is a water-soluble bisphosphonate used in
the treatment of osteoporosis (15). Risedronate was used as a
model drug because water-soluble drugs are more challenging
for incorporation into and release from P (...truncated)