1333151-73-7 br Introduction br Cancer is one of the world
Cancer is one of the world's most fatal diseases, which annually >
10 million new cases have added to its patient population. Therefore, development of therapeutic approaches, that mainly involves re-searches on pharmaceutical systems, is necessary.
Nowadays, 3,4-dihydroxyphenyl-L-alanine known as L-Dopa (Fig. 1) is considered as one of the prominent treatments for many kinds of cancers particularly prostate and breast types and reduce the compli-cations of disease [1–5]. L-Dopa is an important precursor for the var-ious neurotransmitters like adrenaline, noradrenaline, and especially dopamine. These compounds exhibit a novel antitumor activity with considerable influences in several experimental tumor systems . Also, L-Dopa can help to suppression of prolactin concentration, and play a major role in the hormonal control of breast cancer .
The major problem in the cancer therapy with L-Dopa is motor complications which generate in high doses of the drug . Therefore, finding a way to use of L-Dopa and reducing its side eﬀects seems to be essential. Today, new generation of therapeutic systems, focuses on the concept of targeting and slowing the release of drugs to long-term the
therapeutic eﬃciency and reduces the side eﬀect which mainly origi-nates from the high dosage of drug in the blood.
Recent advances in cancer therapeutic manners demonstrate the beneficial eﬀect of formulating drugs in the controlled release drug delivery systems [9–11]. Incorporation of L-Dopa in the controlled re-lease nanocarriers can change the biological distribution of a drug, prolong its therapeutic eﬀects and decrease the instantaneous free concentration of L-Dopa in the blood that leads to minimize the side eﬀects [12–14].
One of the most important factors in the design of drug delivery systems is modifying the drug release profile through the structural or chemical design of the drug carrier. In particular, pH-responsive sys-tems have attracted a lot of interests due to the fact that pH in the diseased tissue particularly in cancer 1333151-73-7 is diﬀerent from blood and normal tissues [15,16]. The use of pH-responsive systems causes reduce undesired drug release during drug transfer in blood circulation and improve the release eﬃciency of the drugs in the diseased tissue or cells. Using these types of delivery systems, the drug is released much faster at diseased cells than the surrounding normal tissues. These features cause to reduce the side eﬀects of therapeutic systems [16–18].
Corresponding author at: Faculty of Chemistry, Razi University, Kermanshah, Iran. E-mail address: [email protected] (N. Shahabadi).
N. Shahabadi, et al.
Fig. 1. Chemical structures of L-Dopa.
Nowadays, the new class of delivering systems that have attracted a lot of attention is layered materials, which can incorporate many kinds of organic compounds between their layers and transport to the specific targets. Because of the controllable release of drugs in layered mate-rials, these new delivering systems have a great potential as a carrier in the pharmaceutical field. One of the most important types of layered compounds is layered double hydroxides (LDHs). The use of LDHs as-sociated with organic biologically active compounds is an eﬃcient al-ternative for common drug delivery systems that may be applied to drug therapies for diﬀerent diseases. A novel approach is the use of magnetic cores like Fe3O4 nanoparticles in LDH structures which can help with the accurate and easy transfer of drugs to target tissue using an external magnet. This feature addressing a great deal of drug transportation problems faced with many delivering systems.
In order to develop a new and eﬃcient protocol based on using the magnetic nanoparticles in drug delivery systems [19–21] and ema-nating from the interest in the LDH-based nanocarriers [22–24], the new core-shell structure composed of Fe3O4, CaAl-LDH and L-Dopa ([email protected]@L-Dopa) was synthesized. The structural features of [email protected]@L-Dopa were char-acterized using X-ray diﬀraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Zeta potential analysis, scanning electron mi-croscopy (SEM), electron dispersive X-ray spectroscopy (EDX), trans-mission electron microscopy (TEM), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), vibrating sample magneto-metry (VSM), pore volume and specific surface area determination by Brunauer-Emmett-Teller (BET) and Barrett-Joyner-Halenda (BJH) methods and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The controlled release properties of [email protected]@L-Dopa as an eﬃcient pH-responsive cancer therapy system were in-vestigated using spectroscopic techniques such as absorption spectro-scopy. Moreover, cell culture and the cytotoxic activity of Fe3O4, L-Dopa, [email protected] and [email protected]@L-Dopa were de-termined and their eﬀects on cancer cell viability were examined on Mel-Rm cell lines.