The Electrospray (ES) technique is a promising particle generation method for drug delivery due to its capabilities of producing monodisperse PLGA composite particles with unique configurations and high drug encapsulation efficiency. In the dissertation work, the coaxial dual capillary ES was used to generate drug-loaded core-shell PLGA particles to study the effects of particle filling materials, drug loading locations and particle shell thicknesses on the resultant in vitro release behaviors of the hydrophilic and/ or hydrophobic model drugs. Through release profile characterization of drug-loaded PLGA particles (particle size: 400 nm and 1 μm), it was confirmed that the co-encapsulation of Budesonide (BUD, the hydrophobic small-molecule model drug) and Theophylline (THY, the hydrophilic small-molecule model drug) in the particle cores is the most effective drug loading strategy for extended release of the fixed combined BUD and THY. Particles composed of PLGA fillers with lower molecular weights and with greater shell layer thicknesses could release THY in a well controlled fashion. On the other hand, a slower release rate of Bovine Serum Albumin (BSA, the protein model drug) from PLGA particles with greater shell thickness was also observed. Sequential release of BSA and Paclitaxel (PTX, the hydrophobic small-molecule anti-cancer model drug) was achieved by the 400-nm PLGA (Mw: 7,000-17,000 g/mol, LA/GA: 50/50) particles with potential biopharmaceutical applications in cancer therapy.