Sustained-Release Hydromorphone Microparticles Produced by Supercritical Fluid Polymer Encapsulation

Han, Yuxiao; Whittaker, Andrew K.; Howdle, Steven M.; Naylor, Andrew; Shabir-Ahmed, Anjumn; Smith, Maree T.

doi:10.1016/j.xphs.2018.09.021

Cited by 14 publications

(1 citation statement)

References 16 publications

(18 reference statements)

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“…In the last two decades, considerable effort has been directed at improving formulation methods for producing polymeric nanoparticles. Versatile methods used to fabricate PLGA nanoparticles include nanoprecipitation, emulsion and hydrogel template methods, the use of supercritical CO 2 , spray drying, coacervation, microfluidics, and the PRINT technique (particle in non-wetting templates) [ 5 , 6 , 7 , 8 , 9 ]. Compared with other methods, the microfluidic method has significant advantages, including the precise control over particle parameters (e.g., size, morphology, and charge) [ 10 , 11 ], monodispersed particles, automated and single-step formulation, as well as relatively high encapsulation efficiency [ 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Optimisation of a Microfluidic Method for the Delivery of a Small Peptide

Han

Kumar

et al. 2021

Pharmaceutics

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Peptides hold promise as therapeutics, as they have high bioactivity and specificity, good aqueous solubility, and low toxicity. However, they typically suffer from short circulation half-lives in the body. To address this issue, here, we have developed a method for encapsulation of an innate-immune targeted hexapeptide into nanoparticles using safe non-toxic FDA-approved materials. Peptide-loaded nanoparticles were formulated using a two-stage microfluidic chip. Microfluidic-related factors (i.e., flow rate, organic solvent, theoretical drug loading, PLGA type, and concentration) that may potentially influence the nanoparticle properties were systematically investigated using dynamic light scattering and transmission electron microscopy. The pharmacokinetic (PK) profile and biodistribution of the optimised nanoparticles were assessed in mice. Peptide-loaded lipid shell-PLGA core nanoparticles with designated size (~400 nm) and a sustained in vitro release profile were further characterized in vivo. In the form of nanoparticles, the elimination half-life of the encapsulated peptide was extended significantly compared with the peptide alone and resulted in a much higher distribution into the lung. These novel nanoparticles with lipid shells have considerable potential for increasing the circulation half-life and improving the biodistribution of therapeutic peptides to improve their clinical utility, including peptides aimed at treating lung-related diseases.

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Section: Introductionmentioning

confidence: 99%

Optimisation of a Microfluidic Method for the Delivery of a Small Peptide

Han

Kumar

et al. 2021

Pharmaceutics

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Enhanced Neovascularization Using Injectable and rhVEGF‐Releasing Cryogel Microparticles

Park

Choi

et al. 2021

Macromolecular Bioscience

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Cryogels are gel networks or scaffolds with a large porous structure; they can be tailored for injectability and for possessing a shape‐memory ability. Herein, a growth factor‐releasing cryogel microparticle (CMP) system is fabricated, and the therapeutic efficacy of recombinant human vascular endothelial growth factor (rhVEGF)‐loaded CMP (V‐CMP) for neovascularization is investigated. To prepare the cryogels, both methacrylated chitosan (Chi‐MA) and methacrylated chondroitin sulfate (CS‐MA) are used, and crosslinking using a radical crosslinking reaction is established. The physical, mechanical, and biological properties of the cryogels are analyzed by varying the amount of CS‐MA used. The cryogels are then pulverized, and microsized CMPs are fabricated. CMPs dispersed in saline demonstrate a shear‐thinning property, and can thus be extruded through a 23G needle. Additionally, V‐CMP exhibit a sustained release profile of rhVEGF and enhance the in vitro proliferation of endothelial cells. Finally, neovascularization and effective tissue necrosis prevention are observed when V‐CMPs are injected into a hindlimb ischemia mouse model. Thus, the injectable V‐CMP system developed herein demonstrates a high potential utility in various tissue regeneration applications based on cell or growth factor delivery.

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