Jiahui Yu

Modified coaxial electrospinning for the preparation of high-quality ketoprofen-loaded cellulose acetate nanofibers

This study investigates the use of a modified coaxial electrospinning process in the production of drug-loaded cellulose acetate (CA) nanofibers. With CA employed as a filament-forming matrix and ketoprofen (KET) as an active pharmaceutical ingredient, modified coaxial processes using sheath fluids comprising only mixed solvents were undertaken. With a sheath-to-core flow rate ratio of 0.2:1, the nanofibers prepared from the coaxial process had a smaller average diameter, narrower size distribution, more uniform structures, and smoother surface morphologies than those generated from single fluid electrospinning. In addition, the coaxial fibers provided a better zero-order drug release profile. The use of a sheath solvent means that the core jet is subjected to electrical drawing for a longer period, facilitating homogeneous core jet solidification and retarding the formation of wrinkles on the surface of the nanofibers. This modified coaxial electrospinning protocol allows the systematic fabrication of functional polymer nanofibers with improved quality.

Effect of polysaccharide nanocrystals on structure, properties, and drug release kinetics of alginate-based microspheres

Polysaccharide nanocrystals, such as rod-like cellulose nanocrystals and chitin whiskers and platelet-like starch nanocrystals, were incorporated into alginate-based nanocomposite microspheres with the aim of enhancing mechanical strength and regulating drug release behavior. The structures and properties of the sols and the resultant nanocomposite microspheres were characterized by rheological testing, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and scanning electron microscopy (SEM). The presence of polysaccharide nanocrystals increased the stability of the crosslinked network structure, and the nanocomposite microspheres consequently exhibited prominent sustained release profiles, as demonstrated by inhibited diffusion of theophylline. Furthermore, based on the drug release results, the release kinetics and transport mechanisms were analyzed and discussed.

Electrospun chitosan-graft-poly (ɛ-caprolactone)/poly (ɛ-caprolactone) cationic nanofibrous mats as potential scaffolds for skin tissue engineering

This research is aimed to develop cationic nanofibrous mats with improved cellular adhesion profiles and stability of three-dimensional fibrous structure as potential scaffolds for skin tissue engineering. Firstly, amino-remained chitosan-graft-poly (ɛ-caprolactone) (CS-g-PCL) was synthesized with a facile one-step manner by grafting ɛ-caprolactone oligomers onto the hydroxyl groups of CS via ring-opening polymerization by using methanesulfonic acid as solvent and catalyst. And then, CS-g-PCL/PCL nanofibrous mats were obtained by electrospinning of CS-g-PCL/PCL mixed solution. Scanning electron microscopy (SEM) images showed that the morphologies and diameters of the nanofibers were mainly affected by the weight ratio of CS-g-PCL to PCL. The enrichment of amino groups on the nanofiber surface was confirmed by X-ray photoelectron spectroscopy (XPS). With the increase of CS-g-PCL in CS-g-PCL/PCL nanofiber, the content of amino groups on the nanofiber surface increased, which resulted in the increase of zeta-potential of nanofibers. Studies on cell-scaffold interaction were carried out by culturing mouse fibroblast cells (L929) on CS-g-PCL/PCL nanofibrous mats with various contents of CS-g-PCL by assessing the growth, proliferation and morphologies of cells. The results of MTS assay and SEM observation showed that CS-g-PCL/PCL (2/8) mats with a moderate surface zeta-potential (ζ=3mV) were the best in promoting the cell attachment and proliferation. Toluidine blue staining further confirmed that L929 cells grew well and exhibited a normal morphology on the CS-g-PCL/PCL (2/8) mats. These results suggested the potential utilization of CS-g-PCL/PCL (2/8) nanofibrous mats for skin tissue engineering.

Preparation, modification, and application of starch nanocrystals in nanomaterials: a review

During the past decade, much work has been devoted to the preparation of nanomaterials by blending starch nanocrystals from different sources with various polymer matrices. The following paper summarizes the most up-to-date information available relating to starch nanocrystals and their contribution to research, application, and advancement of diversified nanomaterials. This paper provides an overview of aspects related to starch nanocrystals, including methods for extraction and preparation, chemical modification (with particular emphasis on the modification methods and strategies), reinforcing effects and mechanisms, and applications and prospects.

Fabrication of cationic nanomicelle from chitosan-graft-polycaprolactone as the carrier of 7-ethyl-10-hydroxy-camptothecin.

In this research, amphiphilic brush-like polycations were synthesized, and used to fabricate cationic nanomicelle as the carrier of 7-ethyl-10-hydroxy-camptothecin (SN-38), in order to enhance its cellular uptake, solubility and stability in aqueous media. In particular, cationic chitosan-graft-polycaprolactone (CS-g-PCL) copolymers were synthesized with a facile one-pot manner via ring-opening polymerization of epsilon-CL onto the hydroxyl groups of CS by using methanesulfonic acid as solvent and catalyst. The formation of CS-g-PCL nanomicelles was confirmed by fluorescence spectrophotoscopy and particle size measurements. It was found that all the nanomicelles showed spherical shapes with narrow size distributions. Their sizes ranged from 47 to 113 nm, and the zeta potentials ranged from 26.7 to 50.8 mV, depending on the grafting content of PCL in CS-g-PCL, suggesting their passive targeting to tumor tissue and endocytosis potential. Water-insoluble antitumor drug, SN-38, was easily encapsulated into CS-g-PCL nanomicelles by lyophilization method. In comparison with bare CS-g-PCL nanomicelles, the corresponding SN-38-loaded nanomicelles showed increased particle sizes and a little reduced zeta potentials. With an increase of grafting PCL content, the drug encapsulation efficiency (EE) and drug loading (DL) of the nanomicelles increased from 64.3 to 84.6% and 6.43 to 8.66%, respectively, whereas their accumulative drug release showed a tendency to decrease due to the enhanced hydrophobic interaction between hydrophobic drug and hydrophobic PCL segments in CS-g-PCL. Also, the CS-g-PCL nanomicelles effectively protected the active lactone ring of SN-38 from hydrolysis under physiological condition, due to the encapsulation of SN-38 into the hydrophobic cores in the nanomicelles. Compared with free SN-38, the SN-38-loaded nanomicelles showed essential decreased cytotoxicity against L929 cell line, and bare CS-g-PCL nanomicelles almost showed non-toxicity. These results suggested the potential utilization of the CS-g-PCL nanomicelles as the carriers of hydrophobic drugs with improving the delivery and release properties.

Electrospun chitosan-graft-poly (ɛ-caprolactone)/poly (ɛ-caprolactone) nanofibrous scaffolds for retinal tissue engineering.

A promising therapy for retinal diseases is to employ biodegradable scaffolds to deliver retinal progenitor cells (RPCs) for repairing damaged or diseased retinal tissue. In the present study, cationic chitosan-graft-poly(ɛ-caprolactone)/polycaprolactone (CS-PCL/PCL) hybrid scaffolds were successfully prepared by electrospinning. Characterization of the obtained nanofibrous scaffolds indicated that zeta-potential, fiber diameter, and the content of amino groups on their surface were closely correlated with the amount of CS-PCL in CS-PCL/PCL scaffolds. To assess the cell–scaffold interaction, mice RPCs (mRPCs) were cultured on the electrospun scaffolds for 7 days. In-vitro proliferation assays revealed that mRPCs proliferated faster on the CS-PCL/PCL (20/80) scaffolds than the other electrospun scaffolds. Scanning electron microscopy and the real-time quantitative polymerase chain reaction results showed that mRPCs grown on CS-PCL/PCL (20/80) scaffolds were more likely to differentiate towards retinal neurons than those on PCL scaffolds. Taken together, these results suggest that CS-PCL/PCL(20/80) scaffolds have potential application in retinal tissue engineering.

Alginate microsphere filled with carbon nanotube as drug carrier

The potential biomedical application of carbon nanotube (CNT) becomes a driving force to incorporate polymer-assisted dispersed CNT into the alginate (AL) microsphere as a drug carrier. The results of XRD and SEM showed that the addition of CNT had no evident effect on the structures and morphologies of microspheres. As expected, the incorporation of CNT enhanced the storage modulus of the AL sol, and hence improved the mechanical stability of the AL/CNT microspheres. Although the swelling degree had no obvious change after the same interval under various pH conditions, the preserving time of the AL/CNT microspheres obviously increased under the pH conditions of 6.8, 7.0 and 7.4. Furthermore, the encapsulation efficiency of drug in the AL/CNT microspheres was enhanced while the drug leakage was decreased. The results of drug release with theophylline as a drug model showed that the AL/CNT microspheres inherited the pH sensitivity of the AL microspheres while the character of sustaining release was more predominant. In virtue of the cytotoxicity of the CNT-filled AL microspheres equivalent to the neat AL microspheres proved by the tests of cell viability assay, the AL/CNT microspheres, with higher stability, less drug leakage and predominant sustaining release profile, showed the potential application as a drug delivery system to intestine and colon.

Facile synthesis of polymer-enveloped ultrasmall superparamagnetic iron oxide for magnetic resonance imaging

Ultrasmall superparamagnetic iron oxide (USPIO) with synthetic polymer, based on magnetite core, was synthesized via facile photochemical in situ polymerization. A possible mechanism of photochemical in situ polymerization was proposed. The obtained polymer-enveloped UPSIO was characterized by transmission electron microscopy (TEM), photo-correlation spectroscopy (PCS), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric (TG) analysis and vibrating sampling magnetometer (VSM) measurement. Properties such as ultrasmall particle size, hydrophilicity, strong magnetization and surface characteristics, which are desirable for magnetic resonance imaging (MRI) contrast agents, were evaluated in detail. The resultant USPIO-based MRI contrast agent holds considerable promise in molecular MR tracking, MR immune imaging, cell tracking and targeted intracellular hyperthermia, etc.

Anti-tumor efficacy of polymer–platinum(II) complex micelles fabricated from folate conjugated PEG-graft-α,β-poly [(N-amino acidyl)-aspartamide] and cis-dichlorodiammine platinum(II) in tumor-bearing mice

To develop a tumor-targeting nano-sized delivery system of cis-dichlorodiammine platinum(II) (CDDP), polymer-metal complex micelles were fabricated from folate-conjugated PEG-graft-α,β-poly [(N-amino acidyl)-aspartamide] (FA-PEG-g-PAAsp) and CDDP. The formation of polymer-metal complex micelles was confirmed by the measurements of critical aggregation concentration (CAC) and particle size, and the morphological observation. It was found that all the micelles showed spherical shapes with clear core-shell structures in narrow size distributions. The typical particle size measured by dynamic laser scattering (DLS) was ca. 105 nm, suggesting their passive targeting to tumor tissue and endocytosis potential. FA-PEG-g-PAAsp-CDDP micelles showed sustained drug release profiles over 40 h, and their accumulative drug release was ranked in the order of FA-PEG-g-PAsp-Ami-CDDP<FA-PEG-g-PAsp-Glu-CDDP<FA-PEG-g-PAsp-Asp-CDDP, depending on the category of used amino acid (Ami: potassium aminomalonate; Glu: glutamic acid; and Asp: aspartic acid). Cellular uptake of FA-PEG-g-PAsp-Ami-CDDP micelles was found to be higher than that of mPEG-g-PAsp-Ami-CDDP micelles because of folate receptor (FR)-mediated endocytosis, which is revealed by the cellular uptake image of Nile red-loaded micelles, and thereby provided higher cytotoxicity against FR-positive KB cells. Although the anti-tumor activity against KB cell-derived tumors was ordered at CDDP>FA-PEG-g-PAAsp-CDDP>mPEG-g-PAAsp-CDDP, the severe toxicity of CDDP in vivo limited its use as ideal anti-tumor drug. Furthermore, FA-PEG-g-PAAsp-CDDP and mPEG-g-PAAsp-CDDP showed rather low toxicity against mice, just similar to that of PBS. It indicated the great potential utilization of the FA-PEG-g-PAAsp-CDDP micelles as the tumor-targeted drug carriers of CDDP with improved anti-tumor efficacy.

Fabrication and evaluation of reduction-sensitive supramolecular hydrogel based on cyclodextrin/polymer inclusion for injectable drug-carrier application

Supramolecular hydrogels based on cyclodextrin/polymer inclusion are an emerging injectable biomaterial for drug controlled-release and cell capsulation. Although the pH- and temperature-sensitivity has been focused on contributing to intelligence, the system sensitive to physiological reduction condition caused by glutathione tripepetide (GSH) has not been reported so far. In this work, novel reduction-sensitive supramolecular hydrogels were, for the first time, fabricated by the inclusion of [poly(ethylene glycol) monomethyl ether]-graft-[disulfide-linked poly(amido amine)] (mPEG-g-SS–PAA) with α-cyclodextrin (α-CD) in aqueous solution. The reduction-sensitivity was ascribed to the disulfide linker in the SS–PAA main chain while various physical conjugations contributed to a reversible gel–sol transition under shearing as a key of injectable function. The drug release from such a supramolecular hydrogel showed a prominent sustained release profile, and the release rate could further be regulated depending upon the reduction condition. It is worth noting that incorporating a low loading-level of reducing agent did not inhibit the formation of hydrogel. As a result, it became possible to use the reduction-sensitivity to regulate the drug release profile in extracellular milieus and normal tissue. Combined with acceptable cytotoxicity, this kind of reduction-sensitive supramolecular hydrogel based on cyclodextrin/polymer inclusion showed a great potential as an injectable smart biomaterial for the application of drug controlled-release.