Design and in vitro evaluation of transdermal patches based on ibuprofen-loaded electrospun fiber mats.

To improve the poor compatibility among different components of Drug-in-adhesive type patch, two novel plasters (Drug-in-fiber and Drug-in-adhesive/fiber) were developed based on ibuprofen (IBU)-loaded fiber mats. These fibrous mats were fabricated via electrospinning of cellulose acetate/poly(vinylpyrrolidone) composites in a binary solvent of N,N-dimethyl acetamide/acetone. Physical status studies suggested that Drug-in-fiber could inhibit IBU re-crystallization, but the active ingredients were released at a relatively slow rate due to the dual-resistance of fiber mat and adhesive matrix. To overcome this shortcoming, Drug-in-adhesive/fiber was designed by coupling medicated hydrophilic pressure sensitive adhesive and IBU-loaded fiber mat. This method endowed Drug-in-adhesive/fiber a fast IBU release rate and high permeated drug amount though simulative skins. This design separated enhancer from adhesive matrix, which guaranteed Drug-in-adhesive/fiber excellent adhesion forces. Hence, the plasters based on medicated fiber mats improved the compatibility among patch components.

Synthesis of the pH-sensitive nanoparticles based on the acylhydrazone bonds conjugated doxorubicin and studies on their in vivo anti-tumor effects.

The purpose of this study was to synthesize DHPD polymers through the conjugation of doxorubicin (DOX) molecules onto poly(ethylene glycol) (PEG) chains via acylhydrazone bonds, and to fabricate pH-responsive DHPD nanoparticles (NPs) for investigation of their biosecurity and in vivo anti-tumor activity. The morphology, size distribution, stability, pH-responsiveness, biosecurity, and in vivo anti-tumor effects of the DHPD NPs were evaluated. Characterization of the DHPD polymers using 1H NMR, FTIR, and Raman spectra confirmed their successful synthesis. The DHPD NPs exhibited a round morphology with an average diameter of 144.4 ± 1.7 nm and a polydispersity index (PDI) of 0.23 ± 0.02. Biosecurity studies indicated that the DHPD NPs were non-toxic to treated mice, and in vitro cell tests demonstrated their ability to be taken up by 4T1 cells. Under the acidic microenvironment of 4T1 cells, the acylhydrazone bonds were cleaved, resulting in increased DOX delivery to tumor cells and improved in vivo anti-tumor effects. Animal experiments confirmed that the DHPD NPs reduced DOX toxicity while enhancing its anti-tumor activity. Furthermore, results from the analysis of γ-interferon (INF-γ), tumor necrosis factor-α (TNF-α), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) indicated that the DHPD NPs improved the anti-4T1 tumor effect of DOX, suggesting their potential application in the treatment of breast cancer.

Docetaxel-loaded redox-sensitive nanoparticles self-assembling from poly(caprolactone) conjugates with disulfide-linked poly(ethylene glycol).

In this study, novel redox-sensitive nanoparticles (NPs) were fabricated from the poly(caprolactone) conjugates with disulfide-linked poly(ethylene glycol) (DDMAT- mPEG-S-S-PCL, DPSP). The DPSP polymer was synthesized by ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. The obtaining of the DPSP polymer was confirmed by the 1H nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopy (FTIR) spectra. The DPSP NPs were fabricated with the solvent-evaporation method. Docetaxel (DTX) was employed as a model drug and encapsulated into the DPSP NPs. The in vitro anti-tumor activity of the DTX-loaded DPSP NPs and free DTX against the breast cancer cells (4T1) were evaluated by MTT assay. The cargo-free DPSP NPs were in circular shapes with an average diameter of 107.8 ± 0.4 nm. These NPs displayed redox-responsive behavior in the presence of glutathione. Animal experiments indicated that the DPSP NPs showed excellent blood compatibility and good bio-security. Cell tests suggested that the DPSP NPs could be taken in by 4T1 cells, smoothly, which improved the anti-tumor activity of free DTX.

Poloxamer188-based nanoparticles improve the anti-oxidation and anti-degradation of curcumin.

Curcumin (CUR) is a food additive approved by World Health Organization. But the shortcomings, such as poor water solubility, easy oxidation and degradation, limit its application. In this study, the CUR-loaded poloxamer188-based nanoparticles (CUR/PTT NPs) were fabricated to improve the stability and water solubility of CUR. Studies found the spherical CUR/PTT NPs had an average size of 98.71 ± 0.64 nm. Stability experiments displayed CUR/PTT NPs were extremely stable in different conditions. XRD analysis indicated the changes of crystal structures of CUR might be the main cause of the improved water solubility. Reducing power and anti-degradation tests suggested CUR/PTT NPs could improve the anti-oxidation and anti-degradation of CUR. Additionally, the results of body weight gains, hematological examination, organ coefficients, hematoxylin and eosin staining demonstrated CUR/PTT NPs bearing the excellent in vivo bio-security. Therefore, this study may provide a new idea for the combination of food industry and nanoparticles.

Harnessing pH-Sensitive Polycation Vehicles for the Efficient siRNA Delivery.

pH-sensitive hydrophobic segments have been certificated to facilitate siRNA delivery efficiency of amphiphilic polycation vehicles. However, optimal design concepts for these vehicles remain unclear. Herein, by studying the library of amphiphilic polycations mPEG-PAMA50-P(DEAx-r-D5Ay) (EAE5x/y), we concluded a multifactor matching concept (pKa values, "proton buffering capacities" (BCs), and critical micelle concentrations (CMCs)) for polycation vehicles to improve siRNA delivery efficiency in vitro and in vivo. We identified that the stronger BCs in a pH 5.5-7.4 subset induced by EAE548/29 (pKa = 6.79) and EAE539/37 (pKa = 6.20) are effective for siRNA delivery in vitro. Further, the stronger BCs occurred in a narrow subset of pH 5.5-6.5 and the lower CMC attributed to higher siRNA delivery capacity of EAE539/37 in vivo than EAE548/29 after intravenous administration and subcutaneous injection. More importantly, 87.2% gene knockdown efficacy was achieved by EAE539/37 via subcutaneous injection, which might be useful for an mRNA vaccine adjuvant. Furthermore, EAE539/37 also successfully delivered siRRM2 to tumor via intravenous administration and received highly efficient antitumor activity. Taken together, the suitable pKa values, strong BCs occurred in pH 5.5-6.5, and low CMCs were probably the potential solution for designing efficient polycationic vehicles for siRNA delivery.

Novel amino-ß-Cyclodextrins containing polymers: Fabrication, characterization, and biological evaluation.

In this study, poly (mPEGMA-co-MAA) (PA) based on monomers of mPEGMA and MAA were synthesized, and different amino-ß-Cyclodextrins with various alkyl chains were conjugated to PA through carbodiimide-mediated coupling reactions. The obtained poly (mPEGMA-co-MAA-g-amino-ß-CD) (PA-g-amino-ß-CD) was characterized by FTIR, NMR and TGA. The fluorescence technique was used to investigate the micellization of PA-g-amino-ß-CDs. The results indicated that these polymers could self-assemble into nano-micelles in water, and PA-g-HDA-ß-CD possessed the lowest CMC value due to its long alkyl chains. In addition, the PA-g-HDA-ß-CD micelles were in spherical shapes with the diameter of 78.5 ± 0.6 nm.The release of the model drug from PA-g-HDA-ß-CD micelles was increased as the pH reduced from 7.4-5.5 at 37 °C. Cytotoxicity and cellular uptake experiments were performed in HepG2, which showed that the cargo-free PA-g-HDA-ß-CD micelles did not have obvious cytotoxicity and were mainly distributed in the cytoplasm of HepG2 cells by endocytosis. Moreover, the study about in vivo distribution of the experimental rats indicated that the accumulation of PA-g-HDA-ß-CD micelles mainly happened in the liver. Therefore, the novel amino-ß-CD containing polymers exhibit good potential applications in drug delivery system.

"Off/on" fluorescence imaging-guided cancer diagnosis and multi-modal therapy.

An efficient theranostic nanoplatform responding to tumour microenvironments with characters of simple and flexible combinations owns great potential in cancer diagnosis and therapy. Herein, a series of triblock copolymers, mPEG-b-PDPA-b-P(nBMA-r-cystamine) (EPB), were synthesized and among them, the structure of EPB-3 was optimized for both fluorescence imaging-guided cancer diagnosis and multi-modal therapy with good biocompatibility. (1) The self-assembled nanoparticles of EPB-3-ICG1 obtained by conjugating one ICG on EPB-3 via S-S bonds effectively performed reduction-sensitive OFF/ON fluorescence signal transition, thus inducing tumour cell-specific amplified fluorescence imaging in vitro and in vivo. (2) By entrapping Au nanorods into the co-assembled NPs of EPB-3 and EPB-3-ICG1, EPB-3-ICG1@Au NPs could synchronously induce strong tumour fluorescence imaging and high local photothermal effect, indicating the potential of imagine-guided photothermal therapy. (3) EPB-3 NPs could efficiently co-load paclitaxel (PTX) and ICG to form stable EPB-3@PTX@ICG NPs, which provided long periods of intracellular pH-sensitive sustainable drug release and highly enhanced apoptosis of 4T1 cells in vitro by the chemo-photothermal effect. Excitingly, a single intravenous injection of EPB-3@PTX@ICG NPs followed by a one-time local near-infrared light (NIR, 808 nm) irradiation treatment for 10 min could lead to significant inhibition of tumour growth, avoiding tumor metastasis and extending the survival of mice. All the above-mentioned results suggest that EPB-3 provides a nanoplatform with the characters of simple structure, convenience of use and flexible combination, holding potential for multi-modal diagnosis and therapy.

Development of curcumin-loaded methoxy poly(ethylene glycol)-block- poly(caprolactone)-block-poly(1, 4, 8-Trioxa [4.6] spiro-9-undecanone) nanoparticles and studies on their in vitro anti-tumor activities.

The purpose of this paper was to fabricate a novel methoxy poly(ethylene glycol)-block-poly(caprolactone)-block-poly(1, 4, 8-Trioxa [4.6] spiro-9-undecanone) (mPEG-b-PCL-b-PTOSUO, mPECT) triblock copolymer and study on the in vitro anti-tumor activity of curcumin-loaded mPECT nanoparticles (NPs). The mPEG-b-PCL-b-PTOSUO NPs were fabricated with solvent evaporation. Transmission electron microscope (TEM) and laser particle analyzer were applied to investigate the morphology and size distribution of the obtained mPECT NPs. The cytotoxicity of the copolymer (mPECT) was reflected by cell viability. Curcumin (CUR), as a model drug, was encapsulated into mPECT NPs. The in vitro anti-tumor activity of CUR-loaded mPECT NPs were also studied. 1H nuclear magnetic resonance (1H NMR), Raman, and Fourier transform infrared spectroscopy (FTIR) spectra confirmed the obtaining of mPECT. TEM photograph showed that most of mPECT NPs were in spherical shapes with a uniform size distribution. High cell viability suggested that the cargo-free mPECT NPs had no obvious cytotoxicity. Fluorescent photographs illustrated that CUR-loaded mPECT NPs could be up-taken by SW1990 cells. The medicated NPs could inhibit the proliferation of SW1990 cells. Therefore, the mPECT NPs could be used as a vehicle to improve the bioavailability and anti-tumor effects of CUR.

Insulin-loaded hydroxypropyl methyl cellulose-co-polyacrylamide-co-methacrylic acid hydrogels used as rectal suppositories to regulate the blood glucose of diabetic rats.

The purpose of this study was developing a novel hydroxypropyl methyl cellulose-co-polyacrylamide-co-methacrylic acid (HPMC-co-PAM-co-PMAA) hydrogel, which was used as rectal suppository to regulate the blood glucose of diabetes. HPMC-co-PAM-co-PMAA hydrogel was fabricated via free-radical polymerization. Fourier transform infrared spectroscopy (FTIR) and Raman spectra were used to confirm the fabrication of HPMC-co-PAM-co-PMAA hydrogel. Their inner morphology was observed with scanning electron microscope (SEM). The extracts of hydrogel were applied to study their cell viability. The hypoglycemic effects of insulin (INS)-loaded HPMC-co-PAM-co-PMAA hydrogels were investigated by rectal administration. FTIR and Raman spectra confirmed the obtaining of HPMC-co-PAM-co-PMAA hydrogels. Many micro-pores were found in the SEM photograph of HPMC-co-PAM-co-PMAA hydrogels. Cell experiments indicated that HPMC-co-PAM-co-PMAA hydrogel was out of cytotoxicity. In vitro release profiles showed that INS-loaded hydrogel could release INS at a continuous manner in pH 7.4 buffer (rectal conditions). Animal experiments suggested that INS-loaded hydrogel had an obvious hypoglycemic effect. Therefore, as a convenient and economic method of administration, INS-loaded HPMC-co-PAM-co-PMAA hydrogels could be used as rectal suppositories to regulate blood glucose.

Methylcellulose and polyacrylate binary hydrogels used as rectal suppository to prevent type I diabetes.

The purpose of this study was to fabricate a novel binary hydrogel, and the insulin-loaded hydrogel was used as rectal suppository to prevent type I diabetes. The binary hydrogel was synthesized via solution polymerization. Its structure was studied by Fourier transform infrared spectroscopy (FTIR) and Raman spectra. The swelling behaviors of binary hydrogels were revealed in pH 1.2, 6.8 and 7.4 buffers, respectively. Their inner morphologies were observed with a scanning electron microscope (SEM). Insulin (INS) was selected as a model drug and encapsulated into the binary hydrogels. INS release study was carried out in pH 7.4 buffer. The hypoglycemic effects of INS-loaded hydrogels were studied by rectal administration. FTIR and Raman spectra confirmed the obtaining of binary hydrogels. The hydrogel showed a high swelling ratio in pH 7.4 (rectum environment). SEM photographs illustrated that many micro-pores in the inner of binary hydrogels, which could accommodate abundant guest molecule (e.g. INS). INS release profile suggested that INS-loaded hydrogels could diffuse INS at a sustained manner. Animal studies proved that INS-loaded binary hydrogel had an obvious hypoglycemic effect. Therefore, it could be speculated that the binary hydrogel had a potential application on treating type I diabetes by rectal administration.

Surface-modified PLGA nanoparticles with chitosan for oral delivery of tolbutamide.

The main purpose of present study was to develop novel chitosan-modified polylactic-co-glycolicacid nanoparticles (CS@PLGA NPs) for improving the bio-availability of tolbutamide (TOL). The TOL-loaded CS@PLGA NPs (TOL-CS@PLGA NPs) were fabricated with the solvent evaporation method. The cargo-free CS@PLGA NPs showed a diameter of 228.3±2.5nm monitored with a laser light particlesizer, and the transmission electron microscope (TEM) photographs revealed their "core-shell" structures. The Zeta potential of the original PLGA NPs and the cargo-free CS@PLGA NPs was measured to be -20.2±3.21mV and 24.2±1.1mV, respectively. The changes in Zeta potential indicated the CS chains were coated on the surfaces of the original PLGA NPs. The thermal gravity analysis (TGA) curves suggested that the CS chains improved the thermostability of the original PLGA NPs. The results of cells viability indicated the cargo-free CS@PLGA NPs were nontoxicity. The in vitro release profiles suggested that TOL-CS@PLGA NPs could release TOL in pH 7.4 phosphate buffer solution (PBS) at a sustained manner. Streptozotocin (STZ) was employed to build the diabetic rat models. The physiological changes in the islet ß cells confirmed the obtaining of diabetic rats. After treatment by gavage, the TOL-CS@PLGA NPs showed an excellent hypoglycemic effect. Therefore, the TOL-CS@PLGA NPs had a potential application in oral delivery of TOL.

Polyelectrolyte complex nanoparticles based on chitosan and methoxy poly(ethylene glycol) methacrylate-co-poly(methylacrylic acid) for oral delivery of ibuprofen.

In this study, the copolymer of methoxy poly(ethylene glycol) methacrylate-co-poly(methylacrylic acid) [poly(mPEGMA-co-MAA)] was synthesized via radical polymerization. Based on this copolymer, novel chitosan-modified poly(mPEGMA-co-MAA) nanoparticles (CS/NPs) were developed to improve the bio-availability of ibuprofen (IBU). Fourier transform infrared spectroscopy (FTIR) and 1H nuclear magnetic resonance (1H NMR) spectra were used to confirm the synthesis of the copolymers. The morphology of CS/NPs was investigated with transmission electron microscopy (TEM). Thermogravimetric analysis (TGA) was used to reveal the thermodynamic properties of the CS/NPs. The cytotoxicity of CS/NPs was assessed by the cell viability of 293T cells. FTIR and 1H NMR spectra confirmed the synthesis of the novel copolymer. TEM photographs showed that the CS/NPs had a core-shell structure. High cell viability indicated that the CS/NPs were nontoxic. The in vitro release profiles suggested that the CS/NPs released IBU in pH 7.4 buffer in a continuous manner. Furthermore, the IBU-CS/NPs showed a long antifebrile effect. Animal experiments showed that the IBU-CS/NPs had obvious antifebrile effects. Therefore, CS/NPs could reduce the dosing frequency of IBU, and improve its bio-availability.

Polyelectrolyte Complex Nanoparticles Based on Methoxy Poly(Ethylene Glycol)-B-Poly (ε-Caprolactone) Carboxylates and Chitosan for Delivery of Tolbutamide.

In this study, a novel chitosan (CS)-modified nanoparticles (NPs) were developed to orally deliver tolbutamide (TOL). Methoxy poly(ethylene glycol)- b-poly(ε-caprolactone) carboxylates (mPEG2000-b-PCL4000) was synthesized via an esterification reaction. CS-modified mPEG2000-b-PCL4000-COOH NPs (CS@NPs) were fabricated by injecting mPEG2000-b-PCL4000-COOH NPs suspension (1.0 mg/mL) into CS solution (1.0 mg/mL, pH 5.0). Fourier transform infrared spectroscopy (FTIR) spectra were used to confirm the obtaining of mPEG2000-b-PCL4000-COOH. Transmission electron microscope (TEM) was carried out to observe morphology of all NPs. Nano ZS90 Malvern ParticleSizer were used to monitor the size distribution of obtained NPs. Thermogravimetry analysis (TGA) was performed to investigate the thermostability of CS@NPs. In vitro TOL release profiles were carried out in pH 1.2 and 7.4 buffers. FTIR spectra confirmed the obtaining of mPEG2000-b-PCL4000-COOH. TGA curves indicated that the protection of CS shells improved the thermostability of mPEG2000-b-PCL4000-COOH NPs. Cell tests indicated the CS@NPs had no obvious cytotoxicity, and they were easily taken up by 293T cells. In vitro release profiles showed that 91.0 ± 1.9% of encapsulated TOL were released from TOL-CS@NPs in pH 7.4 buffer. Therefore, the positive potential of CS@NPs could increase their combining capacity with intestinal mucosal cells. Finally, these NPs would improve the bioavailability of hydrophobic drugs.

Design of poly(mPEGMA-co-MAA) hydrogel-based mPEG-b-PCL nanoparticles for oral meloxicam delivery.

To enhance the therapeutic effects of meloxicam (MLX), we developed an oral MLX-loaded poly(ethylene glycol)-b-poly(ε-caprolactone) nanoparticles@hydrogel (MLX-NPs@hydrogel) preparation. The MLX-NPs were fabricated via a solvent evaporation method, and their morphologies were observed by a JEM-1011 transmission electron microscope (TEM). The poly(mPEGMA-co-MAA) hydrogels were synthesized, and studies on their pH sensibilities were carried out in pH1.2, 6.8, and 7.4 buffers. The final MLX-NPs@hydrogel preparation was obtained by immersing the hydrogels in the MLX-NPs suspensions (pH7.4) for 48h. The thermodynamic properties and cytotoxicity of the MLX-NPs@hydrogel preparation were also studied. TEM images illustrated that mPEG-b-PCL NPs had a uniform size distribution. The poly(mPEGMA-co-MAA) hydrogels showed an excellent pH-sensibility. Thermal gravity analysis (TGA) data suggested that the protection of hydrogels improved the stability of mPEG-b-PCL NPs. The release studies revealed that MLX-NPs@hydrogel could deliver the MLX-NPs into alkalescent environment (e.g. intestinal tract). Then, the medicated NPs released MLX at a sustained release profile. Such preparation could overcome the drawbacks of oral MLX, and enhance its therapeutic effects. Therefore, the NPs@hydrogel was a promising sustained-controlled release matrix.

Design of amphiphilic PCL-PEG-PCL block copolymers as vehicles of Ginkgolide B and their brain-targeting studies.

The amphiphilic PEG-b-PCL block copolymers were synthesized by ring-opening polymerization. The specific and selective antagonists of platelet activating factor, Ginkgolide B (GB), was successfully encapsulated in the synthesized PEG-PCL nanoparticles (NPs) with high Encapsulation Efficiency and Drug Loading. The synthesis of different PEG-PCL copolymers were confirmed with FTIR and 1H NMR spectra. The morphology and particles size distribution of cargo-free PEG-PCL NPs were studied by transmission electron microscope (TEM) analysis and Malvern laser particle analyzer. The bio-distribution and pharmacodynamics studies of GB were studied with Wistar mice as the animal models via tail injecting of GB-PEG-PCL NPs. Results from Malvern laser particle analyzer and TEM analysis illustrated that the cargo-free NPs showed narrow distribution and well separated particles size of about 60 nm in diameter. The in vitro experiment of GB-PEG-PCL NPs exhibited an extended release behavior. The bio-distribution data suggested that Tween-80 covered GB-PEG-PCL NPs showed a brain-targeting behavior. The pharmacodynamics results confirmed that the GB-PEG-PCL NPs had an obvious cerebral protection effect.

Preparation of novel dual-site drug delivery system based on hydroxypropyl methyl cyclodextrin.

An amphipathic copolymer of poly(polyethylene glycol-b-polycaprolactone-co-hydroxypropyl methyl cyclodextrin) [poly(mPEG-b-PCL-co-HPCD)] was synthesized via the free radical polymerization. The copolymer was used to prepare novel nanoparticles (NPs) by a solvent evaporation method. Curcumin (CUR) was selected as a model drug and loaded in the both sites of inner NPs and the cavities of HPCD. 1H nuclear magnetic resonance (1H NMR) study was carried out to confirm the synthesis of poly(mPEG-b-PCL-co-HPCD). The morphology and particle size distribution of the cargo-free NPs were monitored with transmission electron microscopy (TEM) and Malvern particle sizer. The distribution state of CUR in the CUR-loaded NPs was studied with differential scanning calorimetry (DSC) and X-ray diffraction (XRD) methods. The 1H NMR spectrum demonstrated the successful preparation of poly(mPEG-b-PCL-co-HPCD) copolymer. TEM photograph illustrated that the cargo-free NPs had a spherical morphology with an average diameter of 229±32.8nm. The cargo-free NPs had a low critical micelle concentration of 2.9×10-2mg/mL. The HepG2 cells incubated with 1.0mg/mL NPs suspension showed high cell viability. The drug release profile showed that the medicated NPs could continuously release CUR for 24h. Therefore, the poly(mPEG-b-PCL-co-HPCD) NPs had a potential application on the drug delivery.

A novel transdermal drug delivery system based on self-adhesive Janus nanofibrous film with high breathability and monodirectional water-penetration.

Transdermal drug delivery systems (TDDS) had achieved significant success in medical practice, but still suffered from adhesion failure and skin reaction due to the occlusive properties of hydrophobic pressure sensitive adhesives (PSAs). In order to solve these problems, a novel TDDS patch based on self-adhesive Janus nanofibrous film was prepared by a multilayered electrospinning. This multifunctional patch was a bilayer structure. The subjacent layer was a hydrophobic and adhesive fibrous layer electrospun from polyacrylate PSA (HPSA), and the upper backing layer was a hydrophilic cross-linked poly (vinyl alcohol) (c-PVA) nanofibrous film. The structures of the HPSA/c-PVA composite fibrous films were characterized and their application properties, including adherence performance, water vapor permeability, water-penetration, release characteristics, and skin irritation were evaluated. The results indicated that the HPSA/c-PVA composite fibrous films could provide suitable adhesive properties for TDDS application, excellent capacity for drug loading and release, aesthetical appearance and high safety for use on the skin. Especially, due to the nanofibrous network structures and the hydrophobic-hydrophilic wettability gradient from hydrophobic HPSA layer to the hydrophilic c-PVA layer, the Janus films possessed high breathability and monodirectional water-penetration. Water could penetrate from the hydrophobic to the hydrophilic side, but could not permeate through in the opposite direction. This may provide a feasible solution to the problems caused by the water, sweat, or wound exudate on the skin, when the hydrophobic PSAs were used as matrix for TDDS and wound dressing patches.

Preliminary studies on pH-sensitive hydrogels and in vitro release profiles of two model drugs.

The main aim of the present study was to develop a series of pH-sensitive hydrogels for targeted releasing drugs under simulated intestinal environment instead of stomach condition. These hydrogels were prepared via free radical polymerization with polyethylene glycol methacrylate 475 (PEGMA475), PEGMA950 and methacrylic acid as monomers, triethylene glycol dimethacrylate (TRGDMA), and ethylene glycol dimethacrylate as cross-link agents. The surface morphology and internal structures of hydrogels were detected by scanning electron microscope. The swelling experiments were also performed and the results revealed that the smart hydrogels were pH sensitive and their sensitiveness was reversible. Diclofenac sodium and bull serum albumin used as model drugs were loaded in the hydrogels to target releasing them in simulative intestinal tract. In vitro releasing studies showed that medicated hydrogels released model drugs slowly in acid conditions (pH 1.2), while the cumulated release amounts of drugs increased greatly when ambient pH value increased to 7.4. These phenomena indicated that these hydrogels tended to target release stimulating and destructible drugs in intestinal canal instead of gastric environment.

Electrospinning of artemisinin-loaded core-shell fibers for inhibiting drug re-crystallization.

The main aim of this study was to inhibit the re-crystallization of a potent antimalarial drug, artemisinin (ART), by encapsulating it in core-shell fibers via a coaxially electrospun method. The ART-infiltrated cellulose acetate (CA) solution as the core material and poly(vinyl pyrrolidone) (PVP) solution as the shell material were used to prepared ART-loaded core-shell fibers ([ART/CA]/PVP). Transmission electron microscopy images confirmed the core-shell structures of the coaxially electrospun fibers. The scanning electron microscope (SEM), X-ray diffraction, and differential scanning calorimetry were performed to characterize the physical states of ART in the fibers. It was observed that ART crystals were formed in the ART-loaded CA/PVP composite fibers (ART/CA/PVP) during the electrospinning process and increased during storage duration. While ART crystals hardly were observed in the fresh core-shell [ART/CA]/PVP fibers with high ART entrapped amount (20 wt.%) and a little was detected after 6-month storage. Fourier transform infrared spectroscopy (FTIR) results illustrated the hydrogen bonding interaction between ART and CA in the core-shell [ART/CA]/PVP fibers mainly contributed to the amorphous state of ART. Importantly, combination of the hydrophilic PVP shell and the amorphous ART in CA core, the core-shell [ART/CA]/PVP fibers provided a continued and stable ART release manner. Ex vivo permeation studies suggested the amorphous ART in the medicated core-shell fibers could permeate through the stratum corneum smoothly. Hence, the core-shell [ART/CA]/PVP fiber matrix could provide a potential application in transdermal patches.