Encapsulation of Doxorubicin in Furcellaran/Chitosan Nanocapsules by Layer-by-Layer Technique for Selectively Controlled Drug Delivery

Abstract

Minimization of drug side effects is a hallmark of advanced targeted therapy. Herein we describe the synthesis of polysaccharide-based nanocapsules prepared from furcellaran and chitosan via layer-by-layer deposition using electrostatic interaction. Using doxorubicin as a model drug, prepared nanocapsules showed excellent drug loading properties and release influence by pH and stability. Targeted delivery of doxorubicin was achieved by nanocapsule surface modification using homing peptide (seq SMSIARLC). The synthesized nanocapsules possess excellent compatibility to eukaryotic organisms. In the case of nonmalignant cells (PNT1A and HEK-293), toxicity tests revealed the absences of DNA fragmentation, apoptosis, necrosis, and also disruption of erythrocyte membranes. In contrast, results from treatment of malignant cell lines (MDA-MB-231 and PC3) indicate good anticancer effects of synthesized bionanomaterial. Internalization studies revealed the nanocapsule's ability to enter the malignant cell lines by endocytosis and triggering the apoptosis. The occurrence of apoptosis is mostly connected to the presence of ROS and inability of DNA damage reparation. Additionally, the obtained results strongly indicate that peptide modification increases the speed of nanocapsule internalization into malignant cell lines while simultaneously nonmalignant cell lines are untouched by nanocapsules highlighting the strong selectivity of the peptide.

Structure–function relationships in polymeric multilayer capsules designed for cancer drug delivery

“…Engineering of the multilayer capsules allows obtaining multi-purpose systems serving as stimulusresponsive and controllable tools with a high biomedical potential to be used in clinic, in particular, for cancer therapy and diagnosis 11,45,46 . The existing approaches to multilayering and encapsulation enable effective entrapment of lowmolecular-weight anticancer drugs (including doxorubicin 38,47,48 , 5-fluorouracil 49 , curcumin , in multilayer containers. Targeted delivery of the multilayer capsule-based systems to tumor molecular targets still represents a major challenge in modern personalized cancer medicine.…”

“…45 The engineering of the multilayer capsules allows the obtaining of multi-purpose systems serving as stimulus-responsive and controllable tools with a high biomedical potential to be used in the clinic, in particular, for cancer therapy and diagnosis. 11,45,46 The existing approaches to multilayering and encapsulation enable the effective entrapment of low-molecular-weight anticancer drugs (including doxorubicin, 38,47,48 5-fluorouracil, 49 curcumin, 42 thymoquinone, 50 and gemcitabine 46 ), and high-molecular-weight compounds, such as enzymes, 51 small interfering RNAs (siRNAs), 41,52 and antibodies, 53 as well as nanoparticles representing drug-adjuvant complexes, e.g., doxorubicin-bovine serum albumin (BSA) conjugates, 54 in multilayer containers.…”

Influence of Association on Binding of Disaccharides to YKL-39 and hHyal-1 Enzymes

“…For example, positively charged CHI and negatively charged polysaccharides form complexes that can be used as a functional hemostat or as a wound dressing [ 3 ]. CHI/FUR was successfully applied as the nano-capsule carrier and delivery system of doxorubicin [ 4 ].…”

Zwitterionic Nanocapsules with Salt- and Thermo-Responsiveness for Controlled Encapsulation and Release

“…In addition, additional complex steps including soaking, separation, and rinse should always be provided if the extra drug needs to be loaded or reloaded(the revision of the editor is clear and right). On the other hand, Adam et al synthesized polysaccharide-based nanocapsules using the layer-by-layer self-assembly method; 35 however, the strength of the internal shell became weak due to the limited bonding energy of physical interactions. Obviously, it is highly desirable to develop a comprehensive and versatile method to fabricate intelligent polymeric nanocapsules with a well-defined core/shell structure, high stability, and in situ drug-loading capability.…”