An intratumoral injectable, electrostatic, cross-linkable curcumin depot and synergistic enhancement of anticancer activity

Abstract

In this study, we describe an intratumoral injectable, electrostatic, cross-linkable curcumin (Cur) drug depot to enhance anticancer activity. The key concept in this work was the preparation of an electrostatic, cross-linked carboxymethyl cellulose (CMC) and chitosan (CHI) hydrogel containing Cur-loaded microcapsules (Cur-M). The CMC and CHI solutions existed as a liquid before mixing and formed a CMC and CHI (CCH) hydrogel as a drug depot after mixing via electrostatic interactions between the anionic CMC and cationic CHI. Compared with the individual CMC and CHI solutions, the electrostatic, cross-linked CCH depot persisted in vivo for an extended period. The prepared Cur-M was easily mixed with the CMC and CHI solutions. Cur-M/CMC and Cur-;M/CHI solutions easily formed Cur-M-loaded CCH depots after simple mixing. The in vitro and in vivo Cur-M-loaded CCH depot was designed with Cur-M dispersed inside an outer shell of electrostatically cross-linked CCH. The Cur-M-loaded CCH depot produced greater inhibition of tumor growth than did Cur-M, whereas single and repeated injections of free Cur had the weakest inhibitory effects. The results of this study indicate that the electrostatic, cross-linked, Cur-M-loaded CCH depot described in this study can synergistically enhance anticancer activity in chemotherapeutic delivery systems. Preparation of Cur-MCur-M was prepared using a monoaxial one-nozzle atomizer (Sono-Tek Crop, Milton, NY, USA). The typical preparation of Cur-M was achieved as follows: PLGA and Cur were dissolved in ethyl acetate and methanol, respectively. The concentrations of PLGA and Cur were 3% and 5% w/v, respectively. The mixtures of PLGA and Cur were fed into the ultrasonic atomizer at flow rates of 4 ml min − 1 . Microdroplets were produced by atomizing the mixed solutions of PLGA and Cur for~5 s at a vibration frequency of 3 W per 60 kHz and the microdroplets were then immediately collected in a 0.5% w/v poly(vinyl alcohol) solution for 2 min. The distance between the atomizer head and the aqueous poly(vinyl alcohol) solution was 1 cm, and the stirring speed of the poly(vinyl alcohol) solution was 1000 r.p.m. The resulting mixtures were gently stirred for 2 h to allow solidification of the microcapsules and were then filtered and washed with distilled water. The Cur-M was frozen at − 75°C, followed by freeze-drying over 4 days. The morphology of Cur-M was confirmed using an optical microscope (Carl Zeiss MicroimagingThe encapsulation efficiency of Cur was determined using acetonitrile and DW. Cur-M (4 mg) was placed into a test tube and 0.6 ml acetonitrile was added to Injectable, electrostatic, cross-linkable curcumin SH Park et al

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Antitumor Ability of KT2 Peptide Derived from Leukocyte Peptide of Crocodile Against Human HCT116 Colon Cancer Xenografts

“…We selected direct intratumoral injection of peptide into solid tumors based on the fact it may have better benefit than other routes of peptide injection due to reducing non-specific toxicity or unexpected immune response when administered systematically, and the effect of peptide on tumors is exhibited directly (26). Moreover, anticancer drug treatment via intratumoral injection can provide a high local drug level at the tumor site and improve drug effectiveness (27). Finally, intratumoral treatment may be especially beneficial for cancer that occurs in vital organs and which is difficult to treat systemically or surgically (28).…”

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