Controlled-release and preserved bioactivity of proteins from (self-assembled) core-shell double-walled microspheres

Abstract

Abstract:In order to address preserved protein bioactivities and protein sustained-release problems, a method for preparing double-walled microspheres with a core (protein-loaded nanoparticles with a polymer-suspended granule system-formed core) and a second shell (a polymerformed shell) for controlled drug release and preserved protein bioactivities has been developed using (solid-in-oil phase-in-hydrophilic oil-in-water (S/O/O h /W)) phases. The method, based on our previous microsphere preparation method (solid-in-oil phase-in-hydrophilic oil-in-water (S/O/O h /W), employs different concentric poly(D,L-lactide-co-glycolide), poly(D,L-lactide), and protein-loaded nanoparticles to produce a suspended liquid which then self-assembles to form shell-core microspheres in the hydrophilic oil phase, which are then solidified in the water phase. Variations in the preparation parameters allowed complete encapsulation by the shell phase, including the efficient formation of a poly(D,L-lactide) shell encapsulating a protein-loaded nanoparticle-based poly(D,L-lactide-co-glycolide) core. This method produces core-shell doublewalled microspheres that show controlled protein release and preserved protein bioactivities for 60 days. Based upon these results, we concluded that the core-shell double-walled microspheres might be applied for tissue engineering and therapy for chronic diseases, etc.

Formation of methotrexate-PLLA-PEG-PLLA composite microspheres by microencapsulation through a process of suspension-enhanced dispersion by supercritical CO2

“…[1][2][3][4][5] Yin and Yates reported that drug-entrapped biodegradable microcapsules, with sustained drug release, were prepared by spraying a suspension of hollow poly(DL-lactide) particles in procaine hydrochloride aqueous solution into plasticizing solvents. 6 A further report by Zvonar et al described use of a self-microemulsifying system to fabricate Ca-pectinate microcapsules to improve the release and permeability of furosemide.…”

 Sustained-release G-CSF microspheres using a novel solid-in-oil-in-oil-in-water emulsion method

“…25,37 The mixture was stirred at 2000 rpm for 20-30 seconds at 0°C, and then the mixture solution was kept in the refrigerator at −80°C for up to 12 hours. The samples were freeze-dried with Christ (Osterode, Germany) Alpha 1-2 laboratory freeze-drying equipment at 5.25 × 10 −3 Pa pressure for 24 hours.…”

“…The solidified microspheres were washed three times using distilled water and then freeze-dried again before storage (Figure 1). 37 Preparation for G-CSF-loaded PLGA microspheres using W/O/W As control, G-CSF was microencapsulated into PLGA microspheres through a conventional water-in-oil-in-water (W/O/W) method. The 0.1-mL G-CSF water solution (containing 0.25% w/w G-CSF) was added into 0.9 mL PLGA DCM solution (containing 10% w/w PLGA) under stirring with a Fluko FA25 homogenizer at 5000 rpm to prepare a water-in-oil primary emulsion.…”

“…37 The release solution was substituted for fresh release solution every day, and the G-CSF concentration was measured with a G-CSF ELISA kit. For the two release microspheres, the release experiments were repeated four times.…”

Development of a 5-fluorouracil-loaded PLGA microsphere delivery system by a solid-in-oil-in-hydrophilic oil (S/O/hO) novel method for the treatment of tumors

“…We previously developed various preparation methods for biological molecular protein drug delivery such as the waterin-oil-in-hydrophilic oil-in-water (W/O/hO/W) method (34), solid-in-oil-in-oil-in-water (S/O/O/W) method (35)(36)(37), and solid-in-oil-in-hydrophilic oil-in-ethanol (S/O/hO/E) method (38,39,40). The chemical agents were not microencapsulated in the microspheres using these preparation methods.…”