Poly(Octamethylene Citrate)-Based Elastomer Microspheres via Spray-Drying of Chitin Nanocrystal Constructed Pickering Emulsion

Abstract

Poly(octamethylene citrate)(POC) is a promising bioelastomer material in the biomedical field. However, its thermosetting nature poses a significant challenge to processing and molding, especially manufacturing the POC-based elastomer particles as potential, degradable and toughened fillers. Firstly, a Pickering emulsion with a pre-polymer(pre-POC) solution in dimethyl carbonate as a dispersed oil phase, a Pullulan(PUL) aqueous solution as a continuous water phase, and chitin nanocrystal(ChiNC) as a particle-type emulsifier was constructed. Secondly, the POC-based core/shell structured microspheres were prepared by spray-drying of the emulsions, and characterized by a scanning electron microscope and a transmission electron microscope. Finally, the POC-based core/shell structured microspheres were used as elastomer fillers to strengthen and toughen a chitosan film, resulting in 26% increase in the tensile strength and 45% increase in the strain at break; the POC-based core/shell structured microsphere as a double-layer drug release system was built in which the hydrophilic drug of tetracycline hydrochloride(TCH) was released from the outer layer and the hydrophobic drug of curcumin was released from the inner layer, roughly following the Ritger-Peppas model.

Keywords

poly(octamethylene citrate) / elastomer / spray-drying / microsphere / Pickering emulsion

References

[1] YANG J, WEBB A R, AMEER G A. Novel citric acid-based biodegradable elastomers for tissue engineering[J]. Advanced Materials, 2004, 16(6):511-516.

[2] WANG M, XU P, LEI B. Engineering multifunctional bioactive citrate-based biomaterials for tissue engineering[J]. Bioactive Materials, 2023,19:511-537.

[3] WAN L, LU L L, LIANG X J, et al. Citrate-based polyester elastomer with artificially regulatable degradation rate on demand[J]. Biomacromolecules, 2023, 24(9):4123-4137.

[4] WANG H F, HUDDLESTON S, YANG J, et al. Enabling proregenerative medical devices via citrate-based biomaterials:transitioning from inert to regenerative biomaterials[J]. Advanced Materials, 2024, 36(6):2306326.

[5] CHUNG E J, SUGIMOTO M, KOH J L, et al. Low-pressure foaming:a novel method for the fabrication of porous scaffolds for tissue engineering[J]. Tissue Engineering Part C:Methods, 2012, 18(2):113-121.

[6] BALER K, BALL J P, CANKOVA Z, et al. Advanced nanocomposites for bone regeneration[J]. Biomaterials Science, 2014, 2(10):1355-1366.

[7] GUO J S, TIAN X G, XIE D H, et al. Citrate-based tannin-bridged bone composites for lumbar fusion[J]. Advanced Functional Materials, 2020, 30(27):2002438.

[8] VOGT L, BOCCACCINI A R. Random and aligned electrospun poly(ε-caprolactone) (PCL)/poly(1,8-octanediol-co-citrate) (POC) fiber mats for cardiac tissue engineering using benign solvents[J]. European Polymer Journal, 2021,160:110772.

[9] JONES T, ZHANG B S, MAJOR S, et al. All-trans retinoic acid eluting poly(diol citrate) wafers for treatment of glioblastoma[J]. Journal of Biomedical Materials Research Part B:Applied Biomaterials, 2020, 108(3):619-628.

[10] GUO Y, TRAN R T, XIE D H, et al. Citrate-based biphasic scaffolds for the repair of large segmental bone defects[J]. Journal of Biomedical Materials Research Part A, 2015, 103(2):772-781.

[11] KIM K, JEONG C G, HOLLISTER S J. Non-invasive monitoring of tissue scaffold degradation using ultrasound elasticity imaging[J]. Acta Biomaterialia, 2008, 4(4):783-790.

[12] ZHANG B Y, LAI B F L, XIE R X, et al. Microfabrication of AngioChip,a biodegradable polymer scaffold with microfluidic vasculature[J]. Nature Protocols, 2018,13:1793-1813.

[13] MONTGOMERY M, AHADIAN S, DAVENPORT HUYER L, et al. Flexible shape-memory scaffold for minimally invasive delivery of functional tissues[J]. Nature Materials, 2017,16:1038-1046.

[14] ZHU L, ZHANG Y Z, JI Y L. Fabricating poly(1,8-octanediol citrate) elastomer based fibrous mats via electrospinning for soft tissue engineering scaffold[J]. Journal of Materials Science:Materials in Medicine, 2017, 28(6):93.

[15] GUO F R, LIANG K, JI Y L. Electrospun poly(octamethylene citrate) thermoset fibrous mat from chitin nanocrystal constructed Pickering emulsion[J]. Colloid and Polymer Science, 2024, 302(6):891-900.

[16] WU J, MA G H. Recent studies of Pickering emulsions:particles make the difference[J]. Small, 2016, 12(34):4633-4648.

[17] STARVAGGI N C, BRADFORD B J, TAYLOR C D L, et al. Wettability-tuned silica particles for emulsion-templated microcapsules[J]. Soft Matter, 2023, 19(39):7635-7643.

[18] TU S H, ZHAO Y L, TAN H T, et al. Ultralight silica foams with a hierarchical pore structure via a surfactant-free high internal phase emulsion process[J]. Langmuir, 2018, 34(35):10381-10388.

[19] BON S A F, COLVER P J. Pickering miniemulsion polymerization using laponite clay as a stabilizer[J]. Langmuir, 2007, 23(16):8316-8322.

[20] FADIL Y, DINH L N M, YAP M O Y, et al. Ambient-temperature waterborne polymer/rGO nanocomposite films:effect of rGO distribution on electrical conductivity[J]. ACS Applied Materials & Interfaces, 2019, 11(51):48450-48458.

[21] LISUZZO L, CAVALLARO G, MILIOTO S, et al. Pickering emulsions stabilized by halloysite nanotubes:from general aspects to technological applications[J]. Advanced Materials Interfaces, 2022, 9(10):2102346.

[22] SHARKAWY A, BARREIRO M F, RODRIGUES A E. Chitosan-based Pickering emulsions and their applications:a review[J]. Carbohydrate Polymers, 2020,250:116885.

[23] RIGG A, CHAMPAGNE P, CUNNINGHAM M F. Polysaccharide-based nanoparticles as Pickering emulsifiers in emulsion formulations and heterogenous polymerization systems[J]. Macromolecular Rapid Communications, 2022, 43(3):2100493.

[24] KONG L Q, YANG H F, QIAN Z H, et al. Diradical character and controllable magnetic properties in chitin through radical modification[J]. Journal of Donghua University (English Edition), 2022, 39(1):15-21.

[25] LIU X F, BU Y F, JI Y L. Preparation of chitin nanowhiskers via deep eutectic solvent[J]. Journal of Donghua University (Natural Science), 2020, 46(4):584-588. (in Chinese)

[26] SINGH R S, SAINI G K, KENNEDY J F. Pullulan:microbial sources, production and applications[J]. Carbohydrate Polymers, 2008, 73(4):515-531.

[27] PRAJAPATI V D, JANI G K, KHANDA S M. Pullulan:an exopolysaccharide and its various applications[J]. Carbohydrate Polymers, 2013, 95(1):540-549.

[28] GUERRINI L M, OLIVEIRA M P, STAPAIT C C, et al. Evaluation of different solvents and solubility parameters on the morphology and diameter of electrospun Pullulan nanofibers for curcumin entrapment[J]. Carbohydrate Polymers, 2021,251:117127.

[29] LIU Y, WANG Y, ZHAO Y L, et al. Study on the properties of cyanate ester/epoxy adhesive toughened with core-shell rubber particle[J]. Chemistry and Adhesion, 2022, 44(2):115-117,146. (in Chinese)

[30] GU S H, TIAN Y L, LIANG K, et al. Chitin nanocrystals assisted 3D printing of polycitrate thermoset bioelastomers[J]. Carbohydrate Polymers, 2021,256:117549.

[31] MOHAMADY HUSSEIN M A, GULER E, RAYAMAN E, et al. Dual-drug delivery of Ag-chitosan nanoparticles and phenytoin via core-shell PVA/PCL electrospun nanofibers[J]. Carbohydrate Polymers, 2021,270:118373.

[32] CAI J H, YANG Y Q, XIE S T, et al. Research on synthesis and drug release of rutin alginate/chitosan microspheres prepared by layer-by-layer self-assembly method[J]. Polymer Bulletin, 2018(5):58-66. (in Chinese)

[33] LAKSHANI N, WIJERATHNE H S, SANDARUWAN C, et al. Release kinetic models and release mechanisms of controlled-release and slow-release fertilizers[J]. ACS Agricultural Science & Technology, 2023, 3(11):939-956.

[34] YAN W X, SHEN L B, JI Y L, et al. Chitin nanocrystal reinforced wet-spun chitosan fibers[J]. Journal of Applied Polymer Science, 2014, 131(19):40852.