In this study, we developed a lipid-coated hollow calcium phosphate (LCP) nanoparticle for the combined application of two chemotherapeutic drugs to human lung cancer A549 cells. Hydrophilic doxorubicin (DOX) was incorporated into the hollow structure of hollow calcium phosphate (HCP), and a lipid bilayer containing hydrophobic paclitaxel (PTX) was subsequently coated on the surface of HCP. The study on combinational effects demonstrated that the combination of DOX and PTX at a mass ratio of 12:1 showed a synergistic effect against A549 cells. The particle size, zeta potential, and encapsulation efficiency were measured to obtain optimal values: particle size was 335.0 3.2 nm, zeta potential −41.1 mV, and encapsulation efficiency 80.40%±2.24%. An in vitro release study indicated that LCP produced a sustained drug release. A549 cells had a better uptake of LCP with good biocompatibility. Furthermore, in vitro cytotoxicity experiment, apoptosis analysis, in vivo anti-tumor efficacy and protein expression analysis of Bax, Bcl-2, and Caspase-3 demonstrated that the co-delivery system based on LCP had significant synergistic anti-tumor activity. All conclusions suggested that LCP is a promising platform for co-delivery of multiple anti-tumor drugs.

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Naringenin (NRG), a flavonoid compound, had been reported to exhibit extensive pharmacological effects, but its water solubility and oral bioavailability are only~46±6 µg/mL and 5.8%, respectively. The purpose of this study is to design and develop NRG-loaded solid lipid nanoparticles (NRG-SLNs) to provide prolonged and sustained drug release, with improved stability, involving nontoxic nanocarriers, and increase the bioavailability by means of pulmonary administration. Initially, a group contribution method was used to screen the best solid lipid matrix for the preparation of SLNs. NRG-SLNs were prepared by an emulsification and low-temperature solidification method and optimized using an orthogonal experiment approach. The morphology was examined by transmission electron microscopy, and the particle size and zeta potential were determined by photon correlation spectroscopy. The total drug content of NRG-SLNs was measured by high-performance liquid chromatography, and the encapsulation efficiency (EE) was determined by Sephadex gel-50 chromatography and high-performance liquid chromatography. The in vitro NRG release studies were carried out using a dialysis bag. The best cryoprotectant to prepare NRG-SLN lyophilized powder for future structural characterization was selected using differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy. The short-term stability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, cellular uptake, and pharmacokinetics in rats were studied after pulmonary administration of NRG-SLN lyophilized powder. Glycerol monostearate was selected to prepare SLNs, and the optimal formulation of NRG-SLNs was spherical in shape, with a particle size of 98 nm, a polydispersity index of 0.258, a zeta potential of −31.4 mV, a total drug content of 9.76 mg, an EE of 79.11%, and a cumulative drug release of 80% in 48 hours with a sustained profile. In addition, 5% mannitol (w/v) was screened as a cryoprotectant. Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction studies confirmed that the drug was encapsulated into SLNs in an amorphous form. The lyophilized powder was stable at both refrigeration (4°C) and ambient temperature (25°C) for 3 months, and the MTT assay demonstrated that the SLNs were nontoxic. The cellular uptake of fluorescein isothiocyanate-labeled SLNs in A549 cells was highly time dependent over a period of 3 hours, while the pharmacokinetic study in Sprague Dawley rats showed that the relative bioavailability of NRG-SLNs was 2.53-fold greater than that of NRG suspension after pulmonary administration. This study shows that SLNs offer a promising pulmonary delivery system to increase the bioavailability of the poorly water-soluble drug NRG.

Novel core-shell dual-mesoporous silica nanoparticles (DMSN) were successfully prepared as a carrier in order to improve the dissolution of fenofibrate and obtain an oral highly bioavailable controlled-release drug delivery system using the osmotic pump technology. Fenofibrate was loaded into DMSN by an adsorption method. The solid state properties of fenofibrate in DMSN, before and after drug loading, were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption analysis (BET), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). In vitro release tests showed that DMSN increased the dissolution rate of fenofibrate and produced zero-order release in push-pull osmotic pump tablets (OPT). The relative bioavailability of OPT was 186.9% in comparison with the commercial reference product. In summary, osmotic pump technology in combination with solid dispersion technology involving nanometer materials is a promising way for achieving the oral delivery of poorly water-soluble drugs.

In this study, a novel three-dimensional ordered macroporous gelatin (3DOMG) was fabricated as a carrier for increasing the solubility of poorly water-soluble drugs, offering sustained release and a high oral bioavailability. Polymethyl methacrylate nanospheres (257 nm) were used as a colloidal plastic framework to synthesize 3DOMG. Fenofibrate (FNB) was selected as a model drug and loaded onto 3DOMG by the adsorption equilibrium method. Detailed characterization showed that the FNB absorbed onto 3DOMG was in a microcrystalline state. A fluorescence experiment and the prepared drug microcrystal network gave further information on the physical state of the drug. A degradation experiment proved that 3DOMG was readily biodegradable. In vitro release testing showed that 3DOMG increased the dissolution rate of FNB and produced a sustained release. An in vivo pharmacokinetic study confirmed that 3DOMG improved the oral bioavailability compared with that of commercial sustained-release capsules. These findings confirm that 3DOMG can be regarded as a promising carrier for an oral drug delivery system.

Starch macrocellular foam (SMF), a novel natural bio-matrix material, was prepared by the hard template method in order to improve the dissolution rate and oral bioavailability of poorly water-soluble drugs. Nitrendipine (NDP) was chosen as a model drug and was loaded into SMF by the solvent evaporation method. SMF and the loaded SMF samples (NDP-SMF) were characterized by scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy. In vitro drug release studies showed that SMF significantly increased the dissolution rate of NDP. In vivo studies showed that the NDP-SMF tablets clearly increased the oral bioavailability of NDP in comparison with the reference commercial tablets. All the results obtained demonstrated that SMF was a promising carrier for the oral delivery of poor water-soluble drugs.