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.

Purpose: The aim of this study is to develop efficient localized therapy of sertaconazole nitrate for the treatment of vaginal candidiasis. Methods: Sertaconazole nitrate-loaded cationic liposomes were prepared by thin-film hydration method and coated with different concentrations of pectin (0.05%, 0.1% and 0.2%) to develop mucoadhesive liposomes. The formulated mucoadhesive vesicles were characterized in terms of morphology, entrapment efficiency, particle size, zeta value, mucoadhesive properties and drug release. The selected formula was incorporated into a gel base and further characterized by an ex vivo permeation study in comparison with conventional sertaconazole gel. Also, the in vivo study was performed to assess the efficacy of sertaconazole mucoadhesive liposomal gel in treating rats with vaginal candidiasis. Results: The mucoadhesive liposomes were spherical. Coating liposomes with pectin results in increased entrapment efficiency and particle size compared with uncoated vesicles. On the contrary, zeta values were reduced upon coating liposomes with pectin indicating efficient coating of liposomes with pectin. Mucoadhesive liposomes showed a more prolonged and sustained drug release compared with uncoated liposomes. Ex vivo study results showed that mucoadhesive liposomal gel increased sertaconazole tissue retention and reduced drug tissue penetration. In the invivo study, the mucoadhesive liposomal gel showed a significant reduction in the microbial count with a subsequent reduction in inflammatory responses with the lowest histopathological change compared with conventional gel. Conclusion: The study confirmed the potentiality of employing mucoadhesive liposomes as a successful carrier for the vaginal delivery of antifungal drugs.