Metformin hydrochloride-loaded poly(vinyl alcohol) composites as drug delivery systems.

A straightforward method is proposed for the preparation of drug-loaded biocompatible polymer composites based on the freeze drying technique. The solution of poly(vinyl alcohol) (PVA) and metformin hydrochloride (MH) is frozen using liquid nitrogen and the ice crystals are removed by sublimation through freeze drying, which results in the formation of MH-loaded PVA composite. By controlling the PVA concentration in the solution, both MH-loaded PVA fibers and porous products can be obtained. The synthesized MH-loaded PVA composites are characterized with scanning electron microscopy (SEM), powder X-ray diffraction (XRD), Fourier-transformed infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The drug release behavior of the as-prepared products is studied to reveal their potential use in drug delivery system.

Cellulose/gold nanocrystal hybrids via an ionic liquid/aqueous precipitation route.

Injection of a mixture of HAuCl(4) and cellulose dissolved in the ionic liquid (IL) 1-butyl-3-methylimidazolium chloride [Bmim]Cl into aqueous NaBH4 leads to colloidal gold nanoparticle/cellulose hybrid precipitates. This process is a model example for a very simple and generic approach towards (noble) metal/cellulose hybrids, which could find applications in sensing, sterile filtration, or as biomaterials.

Amphiphilic prodrug-decorated graphene oxide as a multi-functional drug delivery system for efficient cancer therapy.

Graphene oxide (GO) has shown great potential in drug delivery. However, the aqueous stability, non-specific drug release and slow release rate are major problems of the GO-based drug delivery system. Herein, we for the first time integrate the dispersant, stabilizing agent and active targeting carrier into a novel drug delivery system based on GO/PP-SS-DOX nanohybrids. The redox-sensitive PP-SS-DOX prodrug was obtained by conjugating mPEG-PLGA (PP) with doxorubicin (DOX) via disulfide bond. PEG-FA provided active targeting property for the constructed drug delivery system, GO/PP-SS-DOX/PEG-FA. In this demonstrated system, PP-SS-DOX markedly increases the stability in physiological solutions of GO and guarantees the DOX release in the reductive environment (cancerous cells). And PEG-FA helps target to cancerous tissues and induces FR-mediated endocytosis. In vitro drug release exhibited the obvious reductive sensitivity and the cumulative release amount was up to 90%, while 40% in previous reports within 72 h. The in vitro cytotoxicity of targeting nanohybrids was significantly cytotoxic than that of non-targeting nanohybrids. In vivo results displayed that the as-prepared targeting nanohybrids showed efficacious antitumor effect while it had nearly no systemic adverse toxicity on B16 tumor-bearing mice. Therefore, the in vitro and in vivo results indicate that our constructed GO/PP-SS-DOX/PEG-FA drug delivery system is a promising carrier in cancer therapy.

Precise ratiometric loading of PTX and DOX based on redox-sensitive mixed micelles for cancer therapy.

PTX and DOX have different anticancer mechanisms. The combination of the two anticancer drugs could synergically enhance their anticancer effect, but simultaneously accompanied by severe side effects. In the present study, we constructed a mixed micelle system based on redox-sensitive mPEG-SS-PTX and mPEG-SS-DOX conjugate. The drug delivery system has a fixed and high drug loading content of 24.2% (PTX∼14.8% and DOX∼9.4%) with a precise ratio of PTX and DOX to realize the synchronized and controlled release. The mixed micelle has an average size of 93.3nm with a narrow distribution, suitable for passive targeting to tumor tissues by the EPR effect. In vitro release profile and in vitro anticancer results show the mixed micelles have obvious redox-sensitive release properties in reducing environment and have a significant cytotoxicity to A549 and B16 cells. Importantly, in vivo study shows the mixed micelles have no obvious side effect on mice compared to free PTX/DOX samples during the treatment. Therefore, the constructed redox-sensitive mixed micelle is a promising drug delivery system for cancer therapy.

Co-delivery of docetaxel and verapamil by reduction-sensitive PEG-PLGA-SS-DTX conjugate micelles to reverse the multi-drug resistance of breast cancer.

The clinical usage of docetaxel (DTX) has been blocked in the clinic because of its poor solubility and tumour multi-drug resistance (MDR). The dominating mechanism of MDR is the over-expression of p-gp on tumour cells. Traditional nano-medicines, such as nanoparticles and micelles, have been used to physically entrap DTX to improve their solubility, while the drug loading content was very low and the tumour resistance was neglected. In this study, the synthesized reduction-sensitive mPEG-PLGA-SS-DTX conjugate was utilized to load the p-gp inhibitor veraparmil (VRP) to prepare DTX and VRP co-delivered mPEG-PLGA-SS-DTX/VRP (PP-SS-DTX/VRP) multi-functional micelles to reverse MDR and enhance the anti-tumour effect of DTX. The micelles had a high drug loading content and showed an obvious reduction-sensitive release property for both DTX and VRP. In addition, an in vitro anti-tumour assay revealed that the micelles markedly inhibited the efflux activity of p-gp and accelerated cell apoptosis, resulting in the improvement of anti-tumour activity and reversal of MDR. The PP-SS-DTX micelles markedly enhanced the in vivo circulation time and increased the drug accumulation in tumour tissues. Therefore, the PP-SS-DTX/VRP micelle is a desirable drug delivery system for multi-drug resistance therapy of DTX and is very promising for clinical usage.

Synthesis of cross-linked enzyme aggregates (CLEAs) in CO2-expanded micellar solutions.

A new method to prepare the cross-linked enzyme aggregates (CLEAs) was developed. Through cross-linking the enzyme (Trypsin) aggregates, which was precipitated from the CO2-expanded reverse micellar solutions, dendritic CLEAs were obtained. The sizes of the CLEAs prepared by this new method were nanometer order of magnitudes and could be tuned by changing the water-to-surfactant ratio (w0) and the concentration of enzyme in the reverse micellar solution. The diameter of CLEAs increased with increasing w0 value of reverse micelles and the concentration of Trypsin. The activity of CLEAs obtained by this method is improved in contrast to those obtained by the conventional method. This method has some advantages in applications and can be easily applied to the synthesis of other cross-linked enzyme aggregates.

Ultrasound-induced capping of polystyrene on TiO2 nanoparticles by precipitation with compressed CO2 as antisolvent.

In this work, a route for the synthesis of inorganic/polymer core/shell composite nanoparticles was proposed, which can be called the antisolvent-ultrasound method. Compressed CO2 was used as antisolvent to precipitate the polymer from its solution dispersed with inorganic nanoparticles, during which ultrasonic irradiation was used to induce the coating of precipitated polymers on the surfaces of the inorganic nanoparticles. TiO2/polystyrene (PS) core/shell nanocomposites have been successfully prepared using this method. The transmission electronic micrographs (TEM) of the obtained nanocomposites show that the TiO2 nanoparticles are coated by the PS shells, of which the thickness can be tuned by the pressure of CO2. The phase structure, absorption properties, and thermal stability of the composite were characterized by X-ray diffraction (XRD), UV-vis spectra, and thermogravimetry, respectively. The results of X-ray photoelectron spectra (XPS) indicate the formation of a strong interaction between PS and TiO2 nanoparticles in the resultant products. This method has some potential advantages for applications and may be easily applied to the preparation of a range of inorganic/polymer core/shell composite nanoparticles.

Huperzine A-phospholipid complex-loaded biodegradable thermosensitive polymer gel for controlled drug release.

The huperzine A-phospholipid complex loaded biodegradable thermosensitive PLGA-PEG-PLGA polymer gel was studied as injectable implant system for controlled release of huperzine-A (HA). First, HA molecules were successfully incorporated into the soybean phosphatidylcholine (SP) molecules to form the huperzine-A-soybean phosphatidylcholine complexes (HA-SPC), which was proved by FT-IR, DSC, XRD, solubility study, TEM, etc. The results indicated that hydrogen bonds and electrostatic interaction between HA and SP molecules play an important role in the formation of HA-SPC. Secondly, the HA-SPC was loaded into biodegradable PLGA-PEG-PLGA thermosensitive gel as injectable implant material to control the release of HA. The in vitro and in vivo drug release behaviors of the prepared products were studied. The in vitro release studies demonstrated that the HA-SPC-loaded gel significantly reduced the initial burst of drug release and extended the release period to about 2 weeks. The in vivo pharmacokinetics study of HA-SPC-loaded gel in rabbits showed that plasma concentration of HA (2.54-0.15ng/mL) was detected for nearly 2 weeks from delivery systems upon single subcutaneous injection. What's more, the in vitro release pattern correlated well with the in vivo pharmacokinetics profile. The present study indicates that HA-SPC loaded PLGA-PEG-PLGA thermal gel may be an attractive candidate vehicle for controlled HA release.

Ibuprofen-loaded poly(lactic-co-glycolic acid) films for controlled drug release.

Ibuprofen- (IBU) loaded biocompatible poly(lactic-co-glycolic acid) (PLGA) films were prepared by spreading polymer/ibuprofen solution on the nonsolvent surface. By controlling the weight ratio of drug and polymer, different drug loading polymer films can be obtained. The synthesized ibuprofen-loaded PLGA films were characterized with scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. The drug release behavior of the as-prepared IBU-loaded PLGA films was studied to reveal their potential application in drug delivery systems. The results show the feasibility of the as-obtained films for controlling drug release. Furthermore, the drug release rate of the film could be controlled by the drug loading content and the release medium. The development of a biodegradable ibuprofen system, based on films, should be of great interest in drug delivery systems.

Synthesis of Ag/BSA composite nanospheres from water-in-oil microemulsion using compressed CO2 as antisolvent.

In this work, a novel route to synthesize biomolecule/metal composite nanospheres is proposed. This method combines the advantages that the silver nanoparticles and bovine serum albumin (BSA) can be precipitated simultaneously from water-in-oil microemulsion by the easy control of CO2 pressure, which was revealed by our high-pressure UV-VIS spectra. The Ag/BSA nanocomposites were successfully prepared using this method. The transmission electronic microscopy (TEM) if the obtained nanocomposites shows that the small-sized Ag nanaoparticles are immobilized by the BSA nanospheres, and the phase structure was characterized by X-ray diffraction (XRD). The Ag/BSA nanocomposites show absorption properties at a wavelength around 435 nm.