Encapsulation and Storage of Therapeutic Fibrin-Homing Peptides using Conducting Polymer Nanoparticles for Programmed Release by Electrical Stimulation

Abstract

CREKA (Cys-Arg-Glu-Lys-Ala) is an important fibrin-homing pentapeptide that has been extensively demonstrated for diagnoses and therapies (e.g. image diagnosis of tumors and to inhibit tumor cell migration and invasion). Although CREKA-loaded nanoparticles (NPs) have received major interest as efficient biomedical systems for cancer diagnosis and treatment, almost no control on the peptide release has been achieved yet. Herein, we report the development of conductive polymer (CP) NPs as therapeutic CREKA carriers for controlled dose administration through electric stimuli.Furthermore, the study has been extended to CR(NMe)EKA (Scheme 1), a previously engineered CREKA analogue in which Glu was replaced by N-methyl-Glu for improvement of the peptide resistance against proteolysis, which is one of the major weaknesses of therapeutic peptide delivery, and for enhancement of the tumor homing capacity by over-stabilizing the bioactive conformation. Particularly, the present work has been focused on understanding the interactions between the newly designed nanoengineered materials and biological fluids and the achievement of a modulated peptide release by fine tuning the electrical stimuli. Two different types of stimuli were compared, chronoamperometry vs cyclic voltammetry, being the latter more effective.

Nanotheranostic Interface Based on Antibiotic‐Loaded Conducting Polymer Nanoparticles for Real‐Time Monitoring of Bacterial Growth Inhibition

“…[ 17 ] Furthermore, this conducting polymer was found to be very effective for the electro‐stimulated release of encapsulated drugs. [ 18,19 ] A representative and common antibiotic, CAM, was loaded into the PEDOT NPs. In this work, unloaded PEDOT NPs (control) and CAM‐loaded PEDOT NPs (hereafter PEDOT/CAM NPs) were prepared by in situ emulsion polymerization as shown in Scheme (details are provided in the Supporting Information).…”

“…It has been previously described that PEDOT NPs can act as excellent therapeutic molecule carriers and attain successful electronic triggered release. [ 18,19 ] However, the encapsulation efficiency for small molecules is challenging, usually leading to low values. In this case, the LC was 11.9 ± 1.3%, which was expressed as mass of loaded CAM with respect to the total mass.…”

“…In this case, the LC was 11.9 ± 1.3%, which was expressed as mass of loaded CAM with respect to the total mass. This value is larger than those achieved for other small drugs, such as curcumin (CUR) and piperine (PIP) (i.e., LC = 5.9 ± 1.6 wt % and 8.0 ± 0.4 wt % for PEDOT/CUR and PEDOT/PIP NPs, respectively) [ 18 ] but lower than obtained for negatively charged pentapeptides, hereafter denoted generically PPEP (LC = 33.8 ± 4.3 wt % and 43.2 ± 2.9 wt %, depending on the PPEP sequence), [ 19 ] which acted as dopant anions.…”

Effects of electrical stimulation on skin surface

“…They delivered an effective dose of verapamil, and concluded that electroosmosis would be safer and more reliable if delivered with high systemic toxicity [ 34 ]. A recent study shows that electrical stimulation can control the rate of peptide release, especially fibrin peptides used for tumor image diagnosis and inhibition of tumor cell migration, displaying a wide space for electrical stimulation therapy [ 35 ]. In fact, the PDP method is the mature therapy in iontophoresis, and local delivery greatly reduces adverse reactions such as skin polarization and redness, and systemic delivery is better than oral and injection.…”

Wirelessly triggered bioactive molecule delivery from degradable electroactive polymer films

“…Stimuli‐responsive drug delivery systems potentially enable the treatment of such conditions because they have potential for spatiotemporally controlled drug delivery 8 . Indeed, materials responding to stimuli (such as enzymes, light, pH, temperature, ultrasound and electric/magnetic fields) have been developed for use as drug delivery devices, 9–24 with reviews specifically on the application of electroactive materials for drug delivery 25–31 …”