ARTICLE Bovine serum albumin gel/polyelectrolyte complex of hyaluronic acid and chitosan based microcarriers for Sorafenib targeted delivery Violeta Pas ¸ cal au 1 | Mihaela Tertis 2 | Emoke Pall 3 | Maria Suciu 4 | Traian Marinca 1 | Marius Pustan 1 | Violeta Merie 1 | Iulia Rus 2 | Cristian Moldovan 5 | Tamara Topala 2 | Codruta Pavel 1 | Catalin Popa 1 1 Technical University of Cluj-Napoca, Cluj-Napoca, Romania 2 “Iuliu Hat ¸ieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania 3 University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca, Cluj- Napoca, Romania 4 National Institute for Research and Development of Isotopic and Molecular Technologies, Cluj-Napoca, Romania 5 MedFuture Research Center for Advanced Medicine/“Iuliu Hat ¸ieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania Correspondence Mihaela Tertis, “Iuliu Hat ¸ieganu” University of Medicine and Pharmacy Cluj-Napoca, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania. Email: mihaela_tso@yahoo.com Funding information Romanian Minister of Research and Innovation, Grant/Award Number: PNIII- P1-1.2-PCCDI-2017-0221/59PCCDI/2018 Abstract The development of systems for targeted delivery of Sorafenib in unresectable hepatocellular carcinoma to reduce the systemic toxicity is a challenge. In our article, we successfully prepared core-shell microcapsules based on bovine serum albumin gel with polyelectrolyte complex multilayer shell of polysac- charides with opposite charges, hyaluronic acid, and chitosan, encapsulating Sorafenib, as targeting delivery system for improved hepatocellular carcinoma therapy. A bovine serum albumin gel core was formed by a method based on a sacrificial CaCO 3 template, followed by the multilayer shell build-up of Ca 2+ cross-linked hyaluronic acid hydrogel, and subsequently alternating multi- layers of the polyelectrolyte complex formed between hyaluronic acid and chitosan. The following techniques: Fourier-transform infrared and UV–Vis spectroscopy, X-ray diffraction, differential scanning calorimetry, confocal laser scanning microscopy, atomic force microscopy, and scanning electron microscopy were used for the physicochemical characterization. These tests revealed the spherical shape of core-shell type, the micro-size, as well as the composition of microcapsules after their synthesis and proved the successful encapsulation and release of the drug. The promising results regarding encap- sulation efficiency, Sorafenib release profile and cytotoxicity on HepG2 and mesenchymal stem cells, recommend Sorafenib loaded microcapsules as suit- able targeted drug carriers for further in vivo studies for hepatocellular carci- noma therapy. KEYWORDS BSA, chitosan, hyaluronic acid, microcapsules, Sorafenib 1 | INTRODUCTION Hepatocellular carcinoma (HCC) ranks fifth for common malignant tumors and is the third most frequent cause of cancer-related death all over the world. [1–3] Sorafenib (Sfb) is the first clinically approved molecular targeted drug for the treatment of HCC. [4] Sfb is a multi-target kinase inhib- itor that can target many growth factor receptors, includ- ing VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-b, c-KIT, FLT-3, and RET, leading to the inhibition of tumor growth Received: 19 November 2019 Revised: 6 January 2020 Accepted: 6 January 2020 DOI: 10.1002/app.49002 J Appl Polym Sci. 2020;e49002. wileyonlinelibrary.com/journal/app © 2020 Wiley Periodicals, Inc. 1 of 16 https://doi.org/10.1002/app.49002