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  • br Introduction br Cancer one of

    2022-05-10


    1. Introduction
    Cancer, one of the deadliest diseases worldwide, is predicted to be the leading cause of death by 2030 [1,2]. Current available treatments including surgery, radiotherapy, chemotherapy, and immunotherapy, come with numerous drawbacks, such as limited effectiveness and un-desirable side effects. In many clinical settings, chemotherapy is the most common approach for metastatic cancers. However, it demon-strates low efficacy due to multidrug resistance and highly toxic to healthy rapidly growing Olaparib because of unspecific targeting [3].
    To overcome these obstacles, colloidal carrier systems have been proposed to deliver the drug to the cancerous tissue. Generally, these delivery systems function within a size range from 10 to 1000 nm and are known to benefit in cancer treatment including: (1) increased drug solubility, (2) improved drug stability, (3) ability to control the drug pharmacokinetics and pharmacodynamics, (4) unique pathways avail-able for uptake by cancerous cells, i.e., endocytosis, and (5) controlled deposition in the tumor area via enhanced permeability and retention effect [4]. Among colloidal drug carriers, polymer-based nanoparticles r> are a promising carrier for chemotherapy due to their bio-suitability, ease of fabrication, and cost-effectiveness [4]. Moreover, their physi-cochemical properties such as size, charge, hydrophilicity and surface can be modified favorably. Nevertheless, many polymers are synthetic, non-biodegradable and non-biocompatable, thus having harmful effects on human and environment [5]. To overcome this drawback, natural polymers such as silk fibroin, have gained increased attention [6].
    Fibroin is a natural protein extracted from Bombyx mori silk. It de-monstrates outstanding properties such as high tensile strength, bio-compatibille, and biodegradable in physiological conditions [6–8]. The applications of fibroin nanoparticles (FNPs) for cancer chemotherapy have been reviewed previously [7,9,10]. Most studies utilize the deso-lvation method to produce FNPs, which leads to unavoidable draw-backs of Olaparib the use of organic solvents, low drug loading, and particle aggregation [7]. In our previous studies, we successfully overcame these problems by the mathematical design and formulation of novel crosslinked FNPs with a mean size of 300 nm and the ability to control the particle surface charge [11,12]. Together these results show pro-mise for the potential use of FNPs in cancer chemotherapy.
    Corresponding author at: 99 Moo 9, Amphoe Muang, Phitsanulok 65000, Thailand. E-mail address: [email protected] (W. Tiyaboonchai).
    Herbal drugs or traditional medicine have been used for a long time in Asia with impressive therapeutic activities. Recently, α-mangostin, obtained from the pericarp of the mangosteen (Garcinia mangostana Linn), shows potential antitumor effects in various kinds of cancers such as breast, colon, skin, lung, and blood [13–17]. The safety of α-man-gostin was confirmed with no detectable unwanted effect at oral dosage up to 80 mg/kg in animal model [18]. Furthermore, a bioavailability clinical trial conducted on 10 healthy adult participants detected no toxicity at the oral dose of approximately 61.5 mg/day [19]. The big-gest drawback of α-mangostin is the low water solubility of 0.2 ± 0.2 μg/mL [20], which leads to a low oral bioavailability in mice [21]. Another disadvantage of α-mangostin is its high hematotoxicity due to the strong surfactant-like action [22]. Over 50% of the human red blood cells were lysed in its antitumor effective dose of 15 μg/mL [23].
    Therefore, to overcome the mentioned problems, both in the che-motherapy issues and α-mangostin itself, α-mangostin loaded cross-linked FNPs were developed for injectable cancer treatment, focus on breast and colon cancers. These particles were prepared using simple desolvation method, followed by characterizations including size, zeta potential, entrapment efficiency (EE%), drug loading capacity (DL%), morphology, drug crystallinity, and dissolution profiles. The impact of intravenous diluent on the FNP properties was also investigated. Additionally, in vitro hemolysis activity in red blood cells, cytotoxicity and DNA fragmentation in Caco-2 colorectal and MCF-7 breast cancer cell lines were studied. Finally, the physicochemical stabilities of FNPs were determined in storage conditions up to 6 months.