Synthesis of sericin-based conjugates by click chemistry: enhancement of sunitinib bioavailability and cell membrane permeation

Abstract

Sericin is a natural protein that has been used in biomedical and pharmaceutical fields as raw material for polypeptide-based drug delivery systems (DDSs). In this paper, it has been employed as pharmaceutical biopolymer for the production of sunitinib-polypeptide conjugate. The synthesis has been carried out by simple click reaction in water, using the redox couple L-ascorbic acid/hydrogen peroxide as a free radical grafting initiator. The bioconjugate molecular weight (50 kDa5Mw5 75 kDa) was obtained by SDS-PAGE, while the spectroscopic characteristics have been studied in order to reveal the presence of grafted sunitinib. In both FT-IR and UV/Vis spectra, signals corresponding to sunitinib functional groups have been identified. Since sunitinib is an anticancer drug characterized by low bioavailability and low permeability, the bioconjugation aimed at their enhancement. In vitro studies demonstrated that bioavailability has been increased to almost 74%, compared with commercial formulation. Also cell membrane permeability has been augmented in in vitro tests, in which membrane models have been used to determine the lipid membrane/physiological fluid partition coefficient (Kp). The log(Kp) value of the bioconjugate was increased to over 4. This effect resulted in a three-fold decrease of IC 50 value against MCF-7 cells.

<p>Comparison of chemoembolization with CalliSpheres® microspheres and conventional chemoembolization in the treatment of hepatocellular carcinoma: a multicenter retrospective study</p>

“…CSMs have the ability to sequester chemotherapeutic agents and release them in a controlled pattern, and thus maintain a sustained high concentration of chemotherapeutics drugs in tumor tissue. 10,14,15 It is also debatable whether DEB-TACE presents with superior survival benefits compared with cTACE in HCC patients. A previous study displayed comparable OS between DEB-TACE with DC Bead ® and cTACE in HCC patients.…”

Special Issue on “Anticancer Drugs Activity and Underlying Mechanisms”

“…Nature is an incredible source of drugs [28][29][30], including interesting bioactive anticancer molecules, even though they sometimes exhibit bioavailability issues that can be overcome by the use of proper vehicles or chemical modifications [31][32][33]. Concerning this, Do et al [34] reported the anticancer properties of 1-(5,7-dimetoxy-2,2dimetyl-2Hcromen-8-yl)-but-2-en-1-on (malloapelta B, malB), isolated from Mallotus apelta, which is able to inhibit the activation of nuclear factor kappa B (NF-kB) and is responsible for downregulating pivotal genes involved in inflammation.…”

Molecularly Imprinted Polymers (MIPs) as Theranostic Systems for Sunitinib Controlled Release and Self-Monitoring in Cancer Therapy

“…In another study, SUT was encapsulated in alginate nanoparticles using calcium chloride as a crosslinker [18], while Alshetaili et al developed three different formulations for SUT delivery to colon cancer cells by the nanoprecipitation technique using various concentrations of poly-lactic-co-glycolic acid (PLGA) and pluronic acid as surfactant [19]. Another interesting strategy involved the synthesis of a sunitinib-sericin conjugate by simple click reaction in water using L-ascorbic acid/hydrogen peroxide as a free radical grafting initiator [20]. On the contrary, only two works report on SUT imprinted polymers [4,5].…”