Abstract
In this study, folate modified bovine serum albumin was successfully synthesized, while preparation of Nintedanib albumin microspheres (ND-FSA NPs) as a carrier was carried out via electrospinning technology. Folate modified albumin was used to enhance the targeting potential of the prepared microspheres. The prepared microspheres had spherical appearance and smooth outer surface. The diameters of microspheres (764.68 ± 88.46 nm) and zeta potential (- 18.38 ± 0.41 mV) were acceptable. The prepared ND-FSA NPs demonstrated a good degree of modification, wherein the modification rate was 28.1%. In vitro release was significantly increased in three different media (double deionized water-DDW, HCl-pH 1.2, and phosphate buffered solution containing 0.5% Tween 80). It is worth noting that incorporation of Nintedanib into folic acid modified albumin microspheres resulted in an enhanced uptake of the drug into MCF-7 breast cancer cells coupled with higher inhibition rate. Altogether, incorporation of Nintedanib into folate modified albumin microspheres is a new approach to improve water solubility and targeting effect of the drug.
Highlights
Nintedanib (C31H33N5O4·C2H6O3S) is a tyrosine kinase inhibitor [1]
In the animal model of PF induced by bleomycin or silica particles, Nintedanib could inhibit extracellular matrix (ECM) deposition and reduce the transdifferentiation of fibroblasts into myofibroblasts [4]
In order to avoid the influence of folate modified albumin, 450 nm was selected as the detection wavelength of Nintedanib, wherein the standard curve was established, while subsequent content determination was carried out
Summary
Nintedanib (C31H33N5O4·C2H6O3S) is a tyrosine kinase inhibitor [1]. Current studies have shown that [2] Nintedanib exerts pleiotropy by inhibiting the activation of fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and Src homologous region 2, including antiangiogenesis and antitumor active domain, like phosphatase-1 (SHP-1).ese factors can block signal of pulmonary fibrosis and reduce the proliferation, diffusion, and transformation of fibroblasts, so as to treat idiopathic pulmonary fibrosis (IPF) [3], thereby showing a strong antifibrotic effect, which potentially delays the disease process of IPF and subsequently treats the disease. In the animal model of PF induced by bleomycin or silica particles, Nintedanib could inhibit extracellular matrix (ECM) deposition and reduce the transdifferentiation of fibroblasts into myofibroblasts [4]. Nintedanib has been explored in the treatment of some cancer types, namely, cancer of the prostate, kidney, and small lung cells [9]. Low solubility of Nintedanib in neutral environment coupled with poor absorption by small intestine makes its bioavailability low (only 4.7%) [10, 11]. One of the main causes of intestinal malabsorption of Nintedanib is its pH-dependent solubility, coupled with intestinal mucus, which hinders its absorption [12]. E intestinal solubility of Nintedanib is dependent on pH, wherein its solubility in aqueous solution increases at acidic pH values below 3 but low at neutral pH [13]. There is an unmet need to improve the Journal of Oncology application of the drug in cancer treatment by enhancing its absorption at the tumor microenvironment (TME)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
