Preparation of protein-loaded sustained-release microspheres via ‘solid-in-oil-in-hydrophilic oil-in-ethanol (S/O/hO/E)’ emulsification

Surgical wound healing using hemostatic gauze scaffold loaded with nanoparticles containing sustained-release granulocyte colony-stimulating factor

“…39 At the same time, the G-CSF diffusion distance from the inner to outer coating decreases due to swelling of the dextran nanoparticles through absorption of water compared with no swelling additives. 42 These resulting in that at the beginning of the release phase, G-CSF were near the coating surface of the G-CSFloaded dextran nanoparticle scaffolds, then the hemostatic gauze scaffold started to degrade and formed more and more new holes in the coating that led to water being permeated into the coating and increased diffusion of G-CSF and dextran swelling (of course, finally dextran also was dissolved and diffused, the PLGA also was degraded, but PLGA degraded slower than the pure scaffold during the whole release process). With these diffusion channels, the diffusion rate of G-CSF became significantly higher than that of high molecular weight dextran, thus the overall release rate was limited by the swelling of dextran.…”

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

“…While the second oil phase of S/O/O/W emulsion was inability to dissolve proteins and dextran, it was used only to extract organic solvent and solidify the microsphere. 34 The solid nanoparticles could not produce high osmotic pressure and dissolved to produce protein molecules being exposed to oil-water interfaces. Therefore, this method might have reduced the amount of protein aggregation and diffusion to the water continuous phase and increased the encapsulation efficiency of microspheres prepared by S/O/O/W.…”

“…24 Furthermore, the S/O/O/W method provided no oil-water and air-water surfaces before the solidifying and hardening of PLGA microspheres, because the second oil phase cannot dissolve proteins and dextran. 34 These factors contributed to improve encapsulation efficiency, release rate, and bioactivity of G-CSF in PLGA microspheres. 34 During release of PLGA microspheres, acid produced in the PLGA degradation process may have accumulated inside the PLGA microspheres, leading to G-CSF denaturation and aggregation.…”

“…34 These factors contributed to improve encapsulation efficiency, release rate, and bioactivity of G-CSF in PLGA microspheres. 34 During release of PLGA microspheres, acid produced in the PLGA degradation process may have accumulated inside the PLGA microspheres, leading to G-CSF denaturation and aggregation. 42 To improve the protein-release profile and decrease the concentration of acid inside the microspheres, preloading proteins into dextran microparticles or nanoparticles before the microencapsulation process might be a good method, because the dispersed dextran phase could be maintained in the microsphere matrix longer than protein retained in the matrix during the period of sustained release.…”

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

“…The specific delivery system can reduce the systemic toxicity and prevent anticancer drug degradation (30-33). However, different methods have different weaknesses such as low encapsulation efficiency, burst release or insufficient duration for drug release.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 (35-37), 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.…”