Xiumei Gai

A novel pH-sensitive carrier for the delivery of antitumor drugs: histidine-modified auricularia auricular polysaccharide nano-micelles

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.

New insights into an innovative Auricularia auricular polysaccharide pH-sensitive hydrogel for controlled protein drug delivery

A novel hydrogel based on Auricularia auricular polysaccharide (AAP), was prepared and characterized. AAP hydrogel exhibited a pH-sensitive release of model protein drug (bovine serum albumin, BSA) under simulated gastrointestinal conditions. The results indicate AAP hydrogel has promising potential as an effective vehicle for oral delivery of protein.

Aqueous Polymer Dispersion Coating Used for Osmotic Pump Tablets: Membrane Property Investigation and IVIVC Evaluation

The objective of this study was to investigate the fundamental properties of propranolol hydrochloride osmotic pump tablets coated by aqueous polymer dispersion, simultaneously exploring the in vitro and in vivo correlation of the tablet. The physicochemical properties and parameters of aqueous polymer dispersion membranes (SEM, water uptake, and water vapor transmission coefficient) were investigated. In addition, the release behavior and the in vitro release and in vivo absorption profiles of the tablets coated by aqueous polymer dispersion were investigated by comparing with propranolol hydrochloride osmotic pump tablets coated by an organic solvent. Results showed that the similarity factor (f2) between cellulose acetate-coated tablet and Eudragit-coated tablet was 78.1, and f2 between cellulose acetate-coated tablet and Kollicoat-coated tablet was 77.6. The linear IVIVC of Eudragit-coated and Kollicoat-coated osmotic pump tablets was determined, which confirmed excellent correlation between the absorption in vivo and the drug release in vitro. Consequently, the membrane coated by aqueous polymer dispersion or organic solvent has similar in vitro release rates of controlled release. Also, compared with organic solvent coating, aqueous polymer dispersion has numerous advantages, such as reduced toxicity and no environmental damage. Therefore, the aqueous polymer dispersion technology has enormous potential as a replacement of organic solvent coating.

pH-sensitive and folic acid-targeted MPEG-PHIS/FA-PEG-VE mixed micelles for the delivery of PTX-VE and their antitumor activity

The aim of this study was to simultaneously introduce pH sensitivity and folic acid (FA) targeting into a micelle system to achieve quick drug release and to enhance its accumulation in tumor cells. Paclitaxel-(+)-α-tocopherol (PTX-VE)-loaded mixed micelles (PHIS/FA/PM) fabricated by poly(ethylene glycol) methyl ether-poly(histidine) (MPEG-PHIS) and folic acid-poly(ethylene glycol)-(+)-α-tocopherol (FA-PEG-VE) were characterized by dynamic light scattering and transmission electron microscopy (TEM). The mixed micelles had a spherical morphology with an average diameter of 137.0±6.70 nm and a zeta potential of −48.7±4.25 mV. The drug encapsulation and loading efficiencies were 91.06%±2.45% and 5.28%±0.30%, respectively. The pH sensitivity was confirmed by changes in particle size, critical micelle concentration, and transmittance as a function of pH. MTT assay showed that PHIS/FA/PM had higher cytotoxicity at pH 6.0 than at pH 7.4, and lower cytotoxicity in the presence of free FA. Confocal laser scanning microscope images demonstrated a time-dependent and FA-inhibited cellular uptake. In vivo imaging confirmed that the mixed micelles targeted accumulation at tumor sites and the tumor inhibition rate was 85.97%. The results proved that the mixed micelle system fabricated by MPEG-PHIS and FA-PEG-VE is a promising approach to improve antitumor efficacy.

Preparation and evaluation of Vinpocetine self-emulsifying pH gradient release pellets

Abstract The main objective of this study was to develop a pH gradient release pellet with self-emulsifying drug delivery system (SEDDS), which could not only improve the oral bioavailability of Vinpocetine (VIN), a poor soluble drug, but reduce the fluctuation of plasma concentration. First, the liquid VIN SEDDS formulation was prepared. Then the self-emulsifying pH gradient release pellets were prepared by extrusion spheronization technique, and formulation consisted by the liquid SEDDS, absorbent (colloidal silicon dioxide), penetration enhancer (sodium chloride), microcrystalline cellulose, ethyl alcohol, and three coating materials (HPMC, Eudragit L30D55, Eudragit FS30D) were eventually selected. Three kinds of coated pellets were mixed in capsules with the mass ratio of 1:1:1. The release curves of capsules were investigated in vitro under the simulated gastrointestinal conditions. In addition, the oral bioavailability and pharmacokinetics of VIN self-emulsifying pH gradient release pellets, commercial tablets and liquid VIN SEDDS were evaluated in Beagle dogs. The oral bioavailability of self-emulsifying pH gradient release pellets was about 149.8% of commercial VIN tablets, and it was about 86% of liquid VIN SEDDS, but there were no significant difference between liquid SEDDS and self-emulsifying pH gradient release pellets. In conclusion, the self-emulsifying pH gradient release pellets could significantly enhance the absorption of VIN and effectively achieve a pH gradient release. And the self-emulsifying pH gradient release pellet was a promising method to improve bioavailability of insoluble drugs.

A novel albumin wrapped nanosuspension of meloxicam to improve inflammation-targeting effects

Background The 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 results MX-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. Conclusion The 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.

Study of controlled-release floating tablets of dipyridamole using the dry-coated method

Abstract Dipyridamole (DIP), having a short biological half-life, has a narrow absorption window and is primarily absorbed in the stomach. So, the purpose of this study was to prepare controlled-release floating (CRF) tablets of dipyridamole by the dry-coated method. The influence of agents with different viscosity, hydroxypropylmethylcellulose (HPMC) and polyvinylpyrollidon K30 (PVP K30) in the core tablet and low-viscosity HPMC and PVP K30 in the coating layer on drug release, were investigated. Then, a study with a three-factor, three-level orthogonal experimental design was used to optimize the formulation of the CRF tablets. After data processing, the optimized formulation was found to be: 80 mg HPMC K4M in the core tablet, 80 mg HPMC E15 in core tablet and 40 mg PVP K30 in the coating layer. Moreover, an in vitro buoyancy study showed that the optimized formulation had an excellent floating ability and could immediately float without a lag time and this lasted more than 12 h. Furthermore, an in vivo gamma scintigraphic study showed that the gastric residence time of the CRF tablet was about 8 h.

Co-delivery of hydrophilic gemcitabine and hydrophobic paclitaxel into novel polymeric micelles for cancer treatment

This study was carried out to investigate an effective method for the co-delivery of Gemcitabine (GEM) and paclitaxel (PTX) into tumor cells. GEM and PTX were modified with functional (+)-α-tocopherol (VE) to obtain similar water solubility. Folic acid-poly(ethylene glycol)–(+)-α-tocopherol (FA–PEG–VE) was designed to co-encapsulate the modified GEM and PTX. Methoxy poly(ethylene glycol)–poly(lactide-co-glycolide) (MPEG–PLGA) was used as a control. The characterizations of micelles were examined by DLS and TEM. It was found that two drugs-loaded FA–PEG–VE micelles, (GPF) and MPEG–PLGA micelles (GPM), had a spherical morphology with an average diameter of 127 nm and 118.9 nm, respectively. GEM–VE and PTX–VE encapsulation efficiencies of GPF were 91.09 ± 0.03%, 92.46 ± 0.02% (88.60 ± 0.03%, 89.32 ± 0.04% of GPM). In vitro release of GPF, 2.73% of GEM–VE and 2.88% of PTX–VE, were accumulatively released in 72 h (4.04% of GEM–VE and 3.88% of PTX–VE from GPM). Furthermore, comparisons of cytotoxicity were made with different fomulations. The IC50 of GPF after 72 h incubation was lowest. FA–PEG–VE micelle showed higher uptake efficiency than that of MPEG–PLGA micelle. Clathrin-mediated and energy-dependent endocytosis was involved in uptake mechanisms. These results demonstrated that GEM–VE and PTX–VE loaded FA–PEG–VE micelles would be a potentially useful prodrug-based nano-drug delivery system for cancer treatment.

A pH-independent instantaneous release of flurbiprofen: a study of the preparation of complexes, their characterization and in vitro/in vivo evaluation

Abstract 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 Cmax and a shortened Tmax 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.