Advances in active targeting of ligand-directed polymeric nanomicelles via exploiting overexpressed cellular receptors for precise nanomedicine.

Many of the utilized drugs which already exist in the pharmaceutical sector are hydrophobic in nature. These drugs are characterized by being poorly absorbed and difficult to formulate in aqueous environments with low bioavailability, which could result in consuming high and frequent doses in order to fulfil the required therapeutic effect. As a result, there is a decisive demand to find modern alternatives to overcome all these drawbacks. Self-assembling polymeric nanomicelles (PMs) with their unique structure appear to be a fascinating choice as a pharmaceutical carrier system for improving the solubility & bioavailability of many drugs. PMs as drug carriers have many advantages including suitable size, high stability, prolonged circulation time, elevated cargo capacity and controlled therapeutic release. Otherwise, the pathological features of some diseased cells, like cancer, allow PMs with particle size <200 nm to be passively uptaken via enhanced permeability and retention phenomenon (EPR). However, the passive targeting approach was proven to be insufficient in many cases. Consequently, the therapeutic efficiency of these PMs can be further reinforced by enhancing their cellular internalization via incorporating targeting ligands. These targeting ligands can enhance the assemblage of loaded cargos in the intended tissues via receptor-mediated endocytosis through exploiting receptors robustly expressed on the exterior of the intended tissue while minimizing their toxic effects. In this review, the up-to-date approaches of harnessing active targeting ligands to exploit certain overexpressed receptors will be summarized concerning the functionalization of the exterior of PMs for ameliorating their targeting potential in the scope of nanomedicine.

Identification of the Molecular Basis of Nanocurcumin-Induced Telocyte Preservation within the Colon of Ulcerative Colitis Rat Model.

BACKGROUND: Telocytes (TCs) are a distinct type of interstitial cells that play a vital role in the pathogenesis of ulcerative colitis and colonic tissue hemostasis. The aim of this study was to examine the effect of nanocurcumin (NC) on the morphometric and immunohistochemical characterization of TCs in the ulcerative colitis (UC) rat model. METHODS: Forty rats were randomly divided into control, NC, UC, and UC+NC groups. At the end of the experiment, the colon was dissected and prepared for histopathological and immunohistochemical assessment. Tissue homogenates were prepared for real-time PCR assessment of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-ß) gene expression. Our results revealed extensive mucosal damage with inflammatory cell infiltration, significant reduction of CD34, and vimentin immunostained TCs in the colon of the UC group with significant elevation of expression of IL-6, TNF-α, and TGF-ß. The UC+NC-treated group revealed significant elevation of TC count compared to the UC group besides, a significant reduction of the three gene expression. CONCLUSION: NC successfully targeted the colonic tissue, improved the mucosal lesion, preserve TCs distribution, and count through its anti-inflammatory and fibrinolytic properties.