ABSTRACT
The escalating incidences of non-alcoholic fatty liver disease (NAFLD) and associated metabolic disorders are global health concerns. Phloretin (Ph) is a natural phenolic compound, that exhibits a wide array of pharmacological actions including its efficacy towards NAFLD. However, poor solubility and bioavailability of phloretin limits its clinical translation. Here, to address this concern we developed an amorphous solid dispersion of phloretin (Ph-SD) using Soluplus® as a polymer matrix. We further performed solid-state characterization through SEM, P-XRD, FT-IR, and TGA/DSC analysis. Phloretin content, encapsulation efficiency, and dissolution profile of the developed formulation were evaluated through reverse phase HPLC. Finally, the oral bioavailability of Ph-SD and its potential application in the treatment of experimental NAFLD mice was investigated. Results demonstrated that the developed formulation (Ph-PD) augments the dissolution profile and oral bioavailability of the native phloretin (Ph). In NAFLD mice, histopathological studies revealed the preventive effect of Ph-SD on degenerative changes, lipid accumulation, and inflammation in the liver. Ph-SD also improved the serum lipid profile, ALT, and AST levels and lowered the interleukin-6 and tumor necrosis factor-α levels in the liver. Further, Ph-SD reduced fibrotic changes in the liver tissues and attenuates NAFLD progression by blocking the mTOR/SREBP-1c pathway. In a nutshell, the results of our study strongly suggest that Ph-SD has the potential to be a therapeutic candidate in the treatment of NAFLD and can be carried forward for further clinical studies.
Subject(s)
Non-alcoholic Fatty Liver Disease , Mice , Animals , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Sterol Regulatory Element Binding Protein 1/metabolism , Biological Availability , Phloretin/pharmacology , Phloretin/therapeutic use , Spectroscopy, Fourier Transform Infrared , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/therapeutic use , Lipids/therapeutic useABSTRACT
Nanocarriers (NCs) containing targeting ligands have received significant attention in recent years because of their ability to enhance cancer cell recognition, which in turn improves both their accuracy and the therapeutic efficacy of their payloads. A promising approach in this area is the use of dual ligands, in which NCs are functionalized with two different targeting ligands, enabling them to specifically recognize and interact with two different biomarkers present on cancer cells for more efficient targeting compared with single-ligand targeted nanocarriers. Herein, we highlight recent advances in dual-ligand targeted NCs with particular emphasis on their potential for improving therapeutic outcomes for cancer therapy.
Subject(s)
Nanoparticles , Neoplasms , Drug Carriers/therapeutic use , Drug Delivery Systems , Humans , Ligands , Neoplasms/drug therapyABSTRACT
Human epidermal growth factor receptor 2 (HER2), a tyrosine kinase receptor with a molecular mass of 185kDa, is overexpressed in several cancers, such as breast, gastric, ovary, prostate, and lung. HER2 is a promising target in cancer therapy because of its crucial role in cell migration, proliferation, survival, angiogenesis, and metastasis through various intracellular signaling cascades. This receptor is an ideal target for the delivery of chemotherapeutic agents because of its accessibility to the extracellular domain. In this review, we highlight different HER2-targeting strategies and various approaches for HER2-targeted delivery systems to improve outcomes for cancer therapy.