Composite core-shell microparticles from microfluidics for synergistic drug delivery

Abstract

Microparticles have a demonstrated value for drug delivery systems. The attempts to develop this technology focus on the generation of featured microparticles for improving the function of the systems. Here, we present a new type of microparticles with gelatin methacrylate (GelMa) cores and poly(L-lactide-co-glycolide) (PLGA) shells for synergistic and sustained drug delivery applications. The microparticles were fabricated by using GelMa aqueous solution and PLGA oil solution as the raw materials of the microfluidic double emulsion templates, in which hydrophilic and hydrophobic actives, such as doxorubicin hydrochloride (DOX, hydrophilic) and camptothecine (CPT, hydrophobic), could be loaded respectively. As the inner cores were polymerized in the microfluidics when the double emulsions were formed, the hydrophilic actives could be trapped in the cores with high efficiency, and the rupture or fusion of the cores could be avoided during the solidification of the microparticle shells with other actives. The size and component of the microparticles can be easily and precisely adjusted by manipulating the flow solutions during the microfluidic emulsification. Because of the solid structure of the resultant microparticles, the encapsulated actives were released from the delivery systems only with the degradation of the biopolymer layers, and thus the burst release of the actives was avoided. These features of the microparticles make them ideal for drug delivery applications.

Biopolymer Microparticles Prepared by Microfluidics for Biomedical Applications

“…One of the most widely used gelatin derivatives, gelatin methacrylate (GelMA) can be synthesized by reacting gelatin with methacrylic anhydride for introducing a methacryloyl substitution group on the reactive amine and hydroxyl groups of the amino acid residues (Figure C). Gelatin core–shell MPs with one or multiple GelMA cores and poly ( l ‐lactide‐ co ‐glycolide) (PLGA) shells were prepared to achieve coencapsulation and synergistic release of multiple drugs . Hydrophilic and hydrophobic drugs, doxorubicin, and camptothecine could be loaded into the core and the shell of the MPs, respectively, and then were released sequentially upon gradual degradation of the shell.…”

Microfluidic generation of Buddha beads-like microcarriers for cell culture

“…Among them, microcarriers have emerged as novel biomimetic platforms, which offer 3D biomaterial scaffolds for cell encapsulation and aggregate formation [10][11][12][13][14][15]. Several approaches have been proposed for fabricating microcarriers, such as photolithography, micromolding, electrojetting and microfluidics [16][17][18][19][20][21][22][23][24]. In comparison with other approaches, microfluidic microcarriers are a promising technique for cell encapsulation because of their advantages of excellent monodispersity, precise size control, high throughput, and better microenvironmental control [21][22][23][24][25][26][27][28].…”

“…Several approaches have been proposed for fabricating microcarriers, such as photolithography, micromolding, electrojetting and microfluidics [16][17][18][19][20][21][22][23][24]. In comparison with other approaches, microfluidic microcarriers are a promising technique for cell encapsulation because of their advantages of excellent monodispersity, precise size control, high throughput, and better microenvironmental control [21][22][23][24][25][26][27][28]. However, because of the lack of effective nutrient exchange pathways, most of the microcarriers are restricted to a small size to avoid the formation of necrotic regions [29][30][31].…”

Responsive Porous Microcarriers With Controllable Oxygen Delivery for Wound Healing

“…It has been demonstrated that GelMa inverse opal particles could be coupled with hemoglobin (Hb, the most important and commonly used oxygen‐carrying protein) via chemical bounding, and the combination between Hb and oxygen would be affected by the changing temperature caused via the photothermal response of MoS 2 , which indicated the controllable oxygen‐delivering capacity of these integrated microcarriers. In addition, it is worth mentioning that GelMa hydrogel has adjustable physical characteristics and great similarity to extracellular matrix, and thus GelMa is endowed with excellent biological properties . Because of the significant biocompatibility which is beneficial to cell proliferation, and the porous structure of the spherical 3D scaffold that provides physical supports for cell adhesion and growth, our desired microcarriers will certainly contribute to tissue repair.…”