Synthesis and Characterization of PLGA Shell Microcapsules Containing Aqueous Cores Prepared by Internal Phase Separation

AAPS PharmSciTech, Sep 2015

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 acetone-water 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.

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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 - 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)


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Samer R. Abulateefeh, Alaaldin M. Alkilany. Synthesis and Characterization of PLGA Shell Microcapsules Containing Aqueous Cores Prepared by Internal Phase Separation, AAPS PharmSciTech, 2015, pp. 891-897, Volume 17, Issue 4, DOI: 10.1208/s12249-015-0413-y