Bovine serum albumin gel/polyelectrolyte complex of hyaluronic acid and chitosan based microcarriers for Sorafenib targeted delivery

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 polysaccharides 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 CaCO3 template, followed by the multilayer shell build‐up of Ca2+ cross‐linked hyaluronic acid hydrogel, and subsequently alternating multilayers 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 encapsulation efficiency, Sorafenib release profile and cytotoxicity on HepG2 and mesenchymal stem cells, recommend Sorafenib loaded microcapsules as suitable targeted drug carriers for further in vivo studies for hepatocellular carcinoma therapy.

Current status of sorafenib nanoparticle delivery systems in the treatment of hepatocellular carcinoma

“…After optimization, the average particle size, zeta potential, drug encapsulation efficiency, and drug loading efficiency of the NPs were 158.00 nm, -16.27 mV, 77.25%, and 7.73%, respectively, and the formulation remained stable at room temperature for more than 1 month. In addition, Pascalau et al prepared spherical core-shell microcapsules based on a BSA gel for targeted delivery of SOR to liver cancer 83 . The microcapsules consisted of a composite multi-layer shell composed of polysaccharides with opposite charges (HA and chitosan) encapsulating SOR.…”

Natural Polymers in Micro- and Nanoencapsulation for Therapeutic and Diagnostic Applications: Part I: Lipids and Fabrication Techniques

“…They reported the formation of stable 300 nmsized particles that demonstrated controlled released of diflunisal in proportion to the number of adsorbed layers. Paşcalău and colleagues [85] recently developed Sorafenib nanocapsules using the LbL deposition. They initially co-precipitated bovine serum, BSA, with the sacrificial calcium carbonate (CaCO 3 ) porous templates to form the BSA gel core microtemplate.…”

Paclitaxel-Loaded Folate-Targeted Albumin-Alginate Nanoparticles Crosslinked with Ethylenediamine. Synthesis and In Vitro Characterization

“…Some studies have indicated that Abraxane ® induced the overexpression of P-glycoprotein and did not allow it to overcome the common small molecule drug resistance problem mediated by P-gp [ 9 ]; in addition, when crosslinked and non-crosslinked PTX-loaded albumin nanoparticles were compared, differences in pharmacokinetics were observed, due to their different physiological ways of delivering the drug to the tumor [ 10 ]. In an attempt to improve the characteristics of nanocarriers, numerous studies have focused on the synthesis of nanosystems formed by proteins and polysaccharides; in this way, core–shell microcapsules based on BSA gel with a polyelectrolyte complex multilayer shell of hyaluronic acid and chitosan, encapsulating Sorafenib, have been designed for hepatocellular cancer therapy [ 11 ]. Ionic crosslinked nanoparticles based on chitosan and BSA were also developed as carriers for doxorubicin, showing their biocompatibility after intravenous administration in a Wistar rat model [ 12 ].…”