The study was aimed to design a novel pH-sensitive carrier to deliver antitumor drugs to increase treatment efficiency. Histidine (His)was used to modify auricularia auricular polysaccharide (AAP) by esterification. Proton nuclear magnetic resonance spectrometry was developed to characterize the His-AAP carrier and the His-AAP Paclitaxel (PTX) micelles were prepared by self-assembled organic solvent evaporation. The formation of His-AAP PTX micelles was confirmed by dynamic light-scattering, transmission electron microscopy and high performance liquid chromatography. It was found that the His-AAP PTX micelles possessed a spherical morphology with an average diameter of 157.2 nm and an 80.3% PTX encapsulation efficiency. In vitro release at pH 7.4, 6.5, 5.0 reached 70%, 71%, and 88%, respectively. The cell viability assay and confocal laser scanning microscope were used to evaluate the cytotoxicity and cell uptake of the His-AAP PTX micelles. Compared with Taxol, the IC50 of the His-AAP PTX micelles were lower after incubating for 24 h, 48 h, or 72 h (0.216 versus 0.199, 0.065 versus 0.060, and 0.023 versus 0.005, respectively). In a test of tumor-bearing mice, the His-AAP PTX micelles significantly inhibited tumor growth. These results showed that His-AAP PTX micelles are a highly promising therapeutic system for anticancer therapy.

The objective of this study was to develop an ocular drug delivery system built on the cationic liposomes, a novel bioadhesive colloidal system, which could enhance the precorneal residence time, ocular permeation, and bioavailability of ibuprofen. The optimal formulation of cationic liposomes prepared by ethanol injection method was ultimately confirmed by an orthogonal L (3) test design. In addition, γ-scintigraphic technology and the microdialysis technique were utilized in the assessment of in vivo precorneal retention capability and ocular bioavailability individually. In the end, we acquired the optimal formulation of ibuprofen cationic liposomes (Ibu-CL) by orthogonal test design, and the particle size and entrapment efficiency (EE%) were 121.0 ± 3.5 nm and 72.9 ± 3.4%, respectively. In comparison to ibuprofen eye drops (Ibu-ED), Ibu-CL could significantly prolong the T to 100 min and the AUC to 1.53-folds, which indicated that the Ibu-CL could improve the precorneal retention time and bioavailability of ibuprofen. Consequently, these outcomes designated that the ibuprofen cationic liposomes we researched probably are a promising application in ocular drug delivery system.

BackgroundThe objective of this study was to develop a more bio-available and safe nanosuspension of meloxicam (MX), which could dramatically improve inflammation targeting.Methods and resultsMX-loaded bovine serum albumin (BSA) nanosuspensions were prepared using acid–base neutralization in aqueous solution and the prepared nanosuspensions were characterized. The results obtained showed that the prepared nanosuspensions had a narrow size distribution with a mean particle size of 78.67±0.22 nm, a polydispersity index of 0.133±0.01, and a zeta potential of −11.87±0.91 mV. The prepared MX nanosuspensions were spherically wrapped by BSA with a smooth surface as shown by transmission electron microscopy. Stability studies showed that the nanosuspensions were physically stable at 4°C with a shelf life of at least 6 months. In the in vitro dissolution test, the MX-loaded BSA nanosuspension (MX-BSA-NS) exhibited sustained release. In addition, an in vivo pharmacokinetic study in rats following intravenous injection showed that the half-life (t1/2), mean residence time (MRT), and area under the concentration–time curve (AUC0–∞) of MX-BSA-NS was increased by 169.83%, 150.13%, and 148.80%, respectively, in comparison with MX conventional solution (MX solution). Furthermore, results from inflammation targeting studies showed that the concentration of MX increased significantly in inflamed tissues but was reduced in normal tissues compared with the MX solution group after injection of MX-BSA-NS.ConclusionThe prepared MX-BSA-NS significantly increased the inflammation-targeting properties and bioavailability of MX, suggesting its potential as a promising formulation for the targeted drug delivery of MX in future clinical applications.

In this study, furbiprofen/hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complexes were prepared to improve the drug dissolution and facilitate its application in hydrophilic gels. Inclusion complexes were prepared using a supercritical fluid processing and a conventional optimized co-lypholization method was employed as a reference. The entrapment efficacy and drug loading of both methods were investigated. Evaluation of drug dissolution enhancement was conducted in deionized water as well as buffer solutions of different pH. Carbopol 940 gels of both flurbiprofen and flurbiprofen/HPβCD inclusion complexes, with or without penetration enhancers, were prepared and percutaneous permeation studies were performed using rat abdominal skin samples. Formation of flurbiprofen/HPβCD inclusion complexes was confirmed by Fourier transform-infrared spectroscopy, differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. The results obtained showed that SCF processing produced a higher EE (81.91 ± 1.54%) and DL (6.96 ± 0.17%) compared with OCL with values of 69.11 ± 2.23% and 4.00 ± 1.01%, respectively. A marked instantaneous release of flurbiprofen/HPβCD inclusion complexes prepared by SCF processing (103.04 ± 2.66% cumulative release within 5 min, a 10-fold increase in comparison with flurbiprofen alone) was observed. In addition, this improvement in dissolution was shown to be pH-independent (the percentage cumulative release at pH 1.2, 4.5, 6.8 and 7.4 at 5 min was 95.19 ± 1.71, 101.75 ± 1.44, 105.37 ± 4.58 and 96.84 ± 0.56, respectively). Percutaneous permeability of flurbiprofen-in-HPβCD-in-gels could be significantly accelerated by turpentine oil and was related to the water content in the system. An in vivo pharmacokinetic study showed a 2-fold increase in C and a shortened T as well as a comparable relative bioavailability when compared with the commercial flurbiprofen Cataplasms (Zepolas). With their superior dissolution, these flurbiprofen/HPβCD inclusion complexes prepared by SCF processing could provide improved applications for flurbiprofen.

Schematic illustration of the preparation and intracellular performance of GEM–VE and PTX–VE loaded FA–PEG–VE micelle.