Heyu Li

Electrospun gelatin nanofibers loaded with vitamins A and E as antibacterial wound dressing materials

Vitamin A palmitate and vitamin E TPGS, common derivatives of the unstable vitamins A and E, were successfully incorporated into biodegradable gelatin nanofibers via electrospinning. Electron microscopy showed that smooth cylindrical fibers were produced, albeit with a small amount of beading visible for the vitamin-loaded systems. The diameters of the fibers decrease with the addition of vitamins. The presence of the vitamins in the fibers was confirmed by IR spectroscopy, and X-ray diffraction showed them to exist in the amorphous physical form post-electrospinning. The addition of vitamins did not affect the hydrophilic properties of the gelatin nanofibers. Fibers containing vitamin A or E alone showed a sustained release profile over more than 60 hours, and those incorporating both vitamins showed similar release characteristics, except that the extent of release for vitamin A was increased. Antibacterial tests demonstrated that materials loaded with vitamin E were effective in inhibiting the growth of E. coli and S. aureus. The fibers could promote the proliferation of fibroblasts during the early stages of culture, and enhance the expression of collagen-specific genes. In vivo tests determined that the fibers loaded with vitamins have better wound healing performance than a commercially used antiseptic gauze and casting films.

Electrospun Poly(N-isopropylacrylamide)/Ethyl Cellulose Nanofibers as Thermoresponsive Drug Delivery Systems

Fibers of poly(N-isopropylacrylamide) (PNIPAAm), ethyl cellulose (EC), and a blend of both were successfully fabricated by electrospinning. Analogous drug-loaded fibers were prepared loaded with ketoprofen (KET). Scanning and transmission electron microscopy showed that the fibers were largely smooth and cylindrical, with no phase separation observed. The addition of KET to the spinning solutions did not affect the morphology of resultant fibers, and no drug particles could be observed to separate from the polymer matrix. X-ray diffraction demonstrated that the drug was present in the amorphous physical form in the fiber matrix. There are significant intermolecular interactions between KET and polymers, as evidenced by IR spectroscopy and molecular modeling. Water contact angle measurements proved that the PNIPAAm and PNIPAAm/EC fibers switched from being hydrophilic to hydrophobic when the temperature was increased through the lower critical solution temperature of 32°C. In vitro drug release studies found that the PNIPAAm/EC blend nanofibers were able to synergistically combine the properties of the 2 polymers, giving temperature-sensitive systems with sustained release properties. In addition, they were established to be nontoxic and suitable for cell growth. This study demonstrates that electrospun-blend PNIPAAm/EC fibers comprise effective and biocompatible materials for drug delivery systems and tissue engineering.

Lactobionic acid and carboxymethyl chitosan functionalized graphene oxide nanocomposites as targeted anticancer drug delivery systems

In this work, we report a targeted drug delivery system built by functionalizing graphene oxide (GO) with carboxymethyl chitosan (CMC), fluorescein isothiocyanate and lactobionic acid (LA). Analogous systems without LA were prepared as controls. Doxorubicin (DOX) was loaded onto the composites through adsorption. The release behavior from both the LA-functionalized and the LA-free material is markedly pH sensitive. The modified GOs have high biocompatibility with the liver cancer cell line SMMC-7721, but can induce cell death after 24h incubation if loaded with DOX. Tests with shorter (2h) incubation times were undertaken to investigate the selectivity of the GO composites: under these conditions, neither DOX-loaded system was found to be toxic to the non-cancerous L929 cell line, but the LA-containing composite showed the ability to selectively induce cell death in cancerous (SMMC-7721) cells while the LA-free analogue was inactive here also. These findings show that the modified GO materials are strong potential candidates for targeted anticancer drug delivery systems.

Thermosensitive nanofibers loaded with ciprofloxacin as antibacterial wound dressing materials

To obtain wound dressings which could be removed easily without secondary injuries, we prepared thermoresponsive electrospun fiber mats containing poly(di(ethylene glycol) methyl ether methacrylate) (PDEGMA). Blend fibers of PDEGMA and poly(l-lactic acid-co-ε-caprolactone) (P(LLA-CL) were fabricated via electrospinning, and analogous fibers containing the antibiotic ciprofloxacin (CIF) were also prepared. Smooth cylindrical fibers were obtained, albeit with a small amount of beading visible for the ciprofloxacin-loaded fibers. X-ray diffraction showed the drug to exist in the amorphous physical form post-electrospinning. The composite fibers showed distinct thermosensitive properties and gave sustained release of CIF over more than 160h in vitro. The fibers could promote the proliferation of fibroblasts, and by varying the temperature cells could easily be attached to and detached from the fibers. Antibacterial tests demonstrated that fibers loaded with ciprofloxacin were effective in inhibiting the growth of E. coli and S. aureus. In vivo investigations on rats indicated that the composite PDEGMA/P(LLA-CL) fibers loaded with CIF had much more potent wound healing properties than a commercial gauze and CIF-loaded fibers made solely of P(LLA-CL). These results demonstrate the potential of PDEGMA/P(LLA-CL)/ciprofloxacin fibers as advanced wound dressing materials.

Poly(N-isopropylacrylamide)/poly(l-lactic acid-co-ɛ-caprolactone) fibers loaded with ciprofloxacin as wound dressing materials

In this work, we aimed to develop new materials to reduce the secondary injuries which can be imparted when replacing wound dressings. Electrospun fibers based on the thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAAm), poly(l-lactic acid-co-ɛ-caprolactone) (PLCL), and the antibiotic ciprofloxacin (CIF) were prepared. The water contact angle of fibers made from a blend of PNIPAAm and PLCL changed dramatically when the temperature was increased above 32°C. Sustained release of CIF from the formulations was observed over >200h. Moreover, L929 fibroblasts could proliferate on the fibers, indicating their biocompatibility. The CIF-loaded fibers were found to have potent antibacterial activity against E. coli and S. aureus. In vivo tests on rats indicated that CIF-loaded thermosensitive fibers have enhanced healing performance compared to CIF-loaded PLCL fibers or a commercial gauze. Electrospun PNIPAAm/PLCL fibers loaded with CIF thus have great promise in the development of new wound dressing materials.

Synthesis and evaluation of temperature- and glucose-sensitive nanoparticles based on phenylboronic acid and N-vinylcaprolactam for insulin delivery

Poly N-vinylcaprolactam-co-acrylamidophenylboronic acid p(NVCL-co-AAPBA) was prepared from N-vinylcaprolactam (NVCL) and 3-acrylamidophenylboronic acid (AAPBA), using 2,2-azobisisobutyronitrile (AIBN) as initiator. The synthesis and structure of the polymer were examined by Fourier Transform infrared spectroscopy (FT-IR) and (1)H-NMR. Dynamic light scattering (DLS), lower critical solution temperature (LCST) and transmission electron microscopy (TEM) were utilized to characterize the nanoparticles, CD spectroscopy was used to determine if there were any changes to the conformation of the insulin, and cell and animal toxicity were also investigated. The prepared nanoparticles were found to be monodisperse submicron particles and were glucose- and temperature-sensitive. In addition, the nanoparticles have good insulin-loading characteristics, do not affect the conformation of the insulin and show low-toxicity to cells and animals. These p(NVCL-co-AAPBA) nanoparticles may have some value for insulin or other hypoglycemic protein delivery.

A thermosensitive drug delivery system prepared by blend electrospinning

In this study, the thermosensitive polymer poly(di(ethylene glycol) methyl ether methacrylate) (PDEGMA) was synthesized and electrospun into fibers by blending with ethyl cellulose (EC). Fibers were additionally prepared loaded with ketoprofen (KET) as a model drug. Smooth cylindrical fibers could generally be observed by electron microscopy, although there were some beads and fused fibers visible in the KET-loaded materials. KET was found to be amorphously distributed in the fibers on the basis of X-ray diffraction data. From water contact angle measurements, it was clear that the wettability of the EC/PDEGMA systems changed as the temperature increased, with the fibers becoming markedly more hydrophobic. In vitro drug release studies showed that KET was released over a prolonged period of time with the fibers having different profiles at 25 and 37°C, reflecting their thermosensitive properties. Furthermore, the materials were found to have good biocompatibility towards L929 fibroblasts. Thus, the fibers prepared in this work have potential as smart stimuli-responsive drug delivery systems.

Regenerated chitin fibers reinforced with bacterial cellulose nanocrystals as suture biomaterials

The objective of this work was to prepare a novel filament with good biocompatibility and mechanical performance which can meet the demands of surgical sutures. Bacterial cellulose nanocrystals (BCNCs) were used to reinforce regenerated chitin (RC) fibers to form BCNC/RC filaments. Mechanical performance measurements demonstrated that the strength of the BCNC/RC filament was increased dramatically over the RC analogue. A yarn made of 30 BCNC-loaded fibers also achieved satisfactory mechanical performance, with a knot-pull tensile strength of 9.8±0.6N. Enzymatic degradation studies showed the BCNC/RC materials to have good biodegradability, the rate of which can be tuned by varying the concentration of BCNCs in the yarn. The RC and the BCNC/RC materials had no cytotoxicity and can promote cell proliferation. In vivo experiments on mice demonstrated that suturing with the BCNC/RC yarn can promote wound healing without obvious adverse effects.

Electrospun gelatin/sodium bicarbonate and poly(lactide-co-ε-caprolactone)/sodium bicarbonate nanofibers as drug delivery systems

In this work, we report electrospun nanofibers made of model hydrophobic (poly(lactide-co-ε-caprolactone); PLCL) and hydrophilic (gelatin) polymers. We explored the effect on drug release of the incorporation of sodium bicarbonate (SB) into these fibers, using the potent antibacterial agent ciprofloxacin as a model drug. The fibers prepared are smooth and have relatively uniform diameters lying between ca. 600 and 850nm. The presence of ciprofloxacin in the fibers was confirmed using IR spectroscopy. X-ray diffraction showed the drug to be incorporated into the fibers in the amorphous form. In vitro drug release studies revealed that, as expected, more rapid drug release was seen with gelatin fibers than those made of PLCL, and a greater final release percentage was obtained. The inclusion of SB in the gelatin fibers imparts them with pH sensitivity: gelatin/SB fibers showed faster release at pH5 than pH7.4, while fibers without SB gave the same release profiles at both pHs. The PLCL fibers have no pH sensitivity, even when SB was included, as a result of their hydrophobic structure precluding the ingress of solvent. In vitro cell culture studies showed that all the fibers are able to promote cell proliferation. The ciprofloxacin loaded fibers are effective in inhibiting Escherichia coli and Staphylococcus aureus growth in antibacterial tests. Thus, the gelatin-based fibers can be used as pH-responsive drug delivery systems, with potential applications for instance in the treatment of tumor resection sites. Should these become infected, the pH would drop, resulting in ciprofloxacin being released and the infection halted.

Insulin-loaded PLGA microspheres for glucose-responsive release

Abstract Porous poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared, loaded with insulin, and then coated in poly(vinyl alcohol) (PVA) and a novel boronic acid-containing copolymer [poly(acrylamide phenyl boronic acid-co-N–vinylcaprolactam); p(AAPBA-co-NVCL)]. Multilayer microspheres were generated using a layer-by-layer approach depositing alternating coats of PVA and p(AAPBA-co-NVCL) on the PLGA surface, with the optimal system found to be that with eight alternating layers of each coating. The resultant material comprised spherical particles with a porous PLGA core and the pores covered in the coating layers. Insulin could successfully be loaded into the particles, with loading capacity and encapsulation efficiencies reaching 2.83 ± 0.15 and 82.6 ± 5.1% respectively, and was found to be present in the amorphous form. The insulin-loaded microspheres could regulate drug release in response to a changing concentration of glucose. In vitro and in vivo toxicology tests demonstrated that they are safe and have high biocompatibility. Using the multilayer microspheres to treat diabetic mice, we found they can effectively control blood sugar levels over at least 18 days, retaining their glucose-sensitive properties during this time. Therefore, the novel multilayer microspheres developed in this work have significant potential as smart drug-delivery systems for the treatment of diabetes.