Tetrac-decorated chitosan-coated PLGA nanoparticles as a new platform for targeted delivery of SN38

Abstract

New integrin-targeted nanoparticles made of chitosan-stabilized PLGA matrix was developed to specifically target colon adenocarcinoma. To this aim, SN38-encapsulated chitosan-coated PLGA NPs were conjugated with tetrac for integrin receptor-guided delivery. To provide a sustained release pattern for SN38, it was loaded into nanoparticles using single emulsion method. The size of NPs were 174.23 ± 6.12 nm with drug encapsulation efficiency and loading content of 73.16 ± 11.15 and 4.45 ± 0.31, respectively. The in vitro results confirmed that the designed nanoplatform showed specific cellular uptake and cytotoxicity in integrin overexpressing cancer cells and provided a sustained release profile for SN38. Additionally, an increased therapeutic potency of targeted formulation over both non-targeted and free drug was shown in vivo.

Nano-Strategies Targeting the Integrin αvβ3 Network for Cancer Therapy

“…In addition to PLGA, other nanoparticles have been investigated to make nanotetrac [ 117 , 118 , 119 ]. Tetrac covalently links to the activated end of pegylated lipid and is used to formulate tetrac-tagged pegylated liposomes (TPL).…”

Synthesis of novel polymeric nanoparticles (methoxy-polyethylene glycol-chitosan/hyaluronic acid) containing 7-ethyl-10-hydroxycamptothecin for colon cancer therapy: in vitro, ex vivo and in vivo investigation

“…80 mL cell suspension including 3 Â 10 5 C26 cells was injected into the mice. After 14 days, when the mean tumour size reached 15 ± 6 mm 3 , mice were divided into four groups (five mice in each group) and 0.2 ml of normal saline 0.9% as a negative control, free SN38 (3 mg/kg), SN38-NPs (3 mg/kg), NPs (without drug;160 mg/kg) was fed by oral route according to the previous literatures [32]. Mice weight and tumour size was evaluated for 30 days.…”

“…Furthermore, the evaluation of the mice interrupted when the tumour size was larger than 2 cm in one dimension or they lost more than 80% of the body weight [31,32].…”

“…The sustained release of SN38-NPs is a result of NPs stability and modification of the SN38-NPs with PEGylated chitosan. Accordingly, PEGylated chitosan can improve the transport of SN38 from the intestine and opens a tight junction [32]. Furthermore, the mPEG brushes are more hydrophilic and cause water penetration into NPs thereby NPs are more flexible and pass the intestinal barrier more easily than free SN38 [7].…”

“…In many types of research, SN38 has been bonded to NPs through a chemical reaction [6,31,32]. In our design, the noncovalent physical adsorption was applied to load drugs in nanoparticles without applying chemical reaction and toxic junction reagents.…”