Introduction: Hepatocellular carcinoma represents a major health problem with the related death numbers still increasing. Active targeting is considered an attractive choice for the development of selective therapeutics with limited side effects and improved efficiency. In this study, we report the design, development and evaluation of a novel dual-ligand functionalized core-shell chitosan-based nanocarrier for the selective delivery of doxorubicin (DOX) for treatment of hepatocellular carcinoma (HCC). Methods: Following factorial design experiments, DOX was initially complexed with negatively charged carboxymethyl chitosan-g-poly(acrylate) and then the complex was coated with a positively charged dual-ligand (lactobionic acid and glycyrrhetinic acid)-conjugated chitosan. The developed active targeting system was then tested in vitro on Hep-G2 cells using flow cytometry and fluorescence imaging. Results: The obtained results proved the ability of the dual-ligand system to enhance the intracellular uptake of the drug by 4-fold and 8-fold after 4 hrs and 24 hrs of incubation, respectively. The efficiency of the dual-ligand functionalized nanoparticles was also tested in vivo on Wistar rats with induced liver tumors. Testing of serum biomarkers (albumin, creatinine, urea, alpha fetoprotein, ALT, AST and ALP) in addition to histopathological microscopic examination of liver, kidney and heart tissues confirmed the enhanced safety of the developed targeted nanocarrier system compared to the conventional DOX. Discussion: The developed targeted system showed improved intracellular drug delivery and uptake as well as enhanced safety profile. The nanoparticles were formed based on electrostatic interactions providing the flexibility that allows their use as a model for delivery of other drugs and other targets.

Quinic acid (QA) and its ester conjugates have been subjected to in-depth scientific investigations for their antioxidant properties. In this study, molecularly imprinted polymers (MIPs) were used for selective extraction of quinic acid (QA) from coffee bean extract. Computational modelling was performed to optimize the process of MIP preparation. Three different functional monomers (allylamine, methacrylic acid (MAA) and 4-vinylpyridine (4-VP)) were tested for imprinting. The ratio of each monomer to template chosen was based on the optimum ratio obtained from computational studies. Equilibrium rebinding studies were conducted and MIP C, which was prepared using 4-VP as functional monomer with template to monomer ratio of 1:5, showed better binding performance than the other prepared MIPs. Accordingly, MIP C was chosen to be applied for selective separation of QA using solid-phase extraction. The selectivity of MIP C towards QA was tested versus its analogues found in coffee (caffeic acid and chlorogenic acid). Molecularly imprinted solid-phase extraction (MISPE) using MIP C as sorbent was then applied for selective extraction of QA from aqueous coffee extract. The applied MISPE was able to retrieve 81.918 ± 3.027% of QA with a significant reduction in the amount of other components in the extract.

In this study we have developed a high-dose dry powder inhaler formulation of indomethacin using a novel approach to carrier-based formulations. Specifically, larger drug particles serve as the carrier for the smaller micronized drug particles, such that an inhaled dose is combined with an oral dose. To study this system, the aerosol performance of a standard indomethacin–lactose formulation was compared to carrier-free micronized indomethacin and a drug-as-carrier formulation (a micronized indomethacin–coarse indomethacin blend). Indomethacin with lactose showed a very poor aerosol performance, indicating high adhesion between the drug and carrier. The performance of the carrier-free micronized drug was significantly better, indicating low cohesion. Coarse drug particles as a carrier allowed improved powder flow and aerosol performance while also providing a potential secondary route of absorption of indomethacin, namely oral. An optimal formulation ratio of 1:1 (w/w) fine indomethacin–coarse indomethacin was developed in this study.