Micelles Formed by Polypeptide Containing Polymers Synthesized Via N-Carboxy Anhydrides and Their Application for Cancer Treatment

Abstract

Abstract:The development of multifunctional polymeric materials for biological applications is mainly guided by the goal of achieving the encapsulation of pharmaceutical compounds through a self-assembly process to form nanoconstructs that control the biodistribution of the active compounds, and therefore minimize systemic side effects. Micelles are formed from amphiphilic polymers in a selective solvent. In biological applications, micelles are formed in water, and their cores are loaded with hydrophobic pharmaceutics, where they are solubilized and are usually delivered through the blood compartment. Even though a large number of polymeric materials that form nanocarrier delivery systems has been investigated, a surprisingly small subset of these technologies has demonstrated potentially curative preclinical results, and fewer have progressed towards commercialization. One of the most promising classes of polymeric materials for drug delivery applications is polypeptides, which combine the properties of the conventional polymers with the 3D structure of natural proteins, i.e., α-helices and β-sheets. In this article, the synthetic pathways followed to develop well-defined polymeric micelles based on polypeptides prepared through ring-opening polymerization (ROP) of N-carboxy anhydrides are reviewed. Among these works, we focus on studies performed on micellar delivery systems to treat cancer. The review is limited to systems presented from 2000-2017.

Marcromolecular Architecture and Encapsulation of the Anticancer Drug Everolimus Control the Self-Assembly of Amphiphilic Polypeptide-Containing Hybrids

“…Due to the natural mechanisms of organisms to resist and destroy anything foreign invading their body, there are several extra- and intracellular barriers that hinder the efficacy of the nanocarriers through the blood compartment . Most of the studies thus far have been focused on the control of the functionality (e.g., pH-, temperature-, redox-responsiveness), − the size and surface chemistry, and the mechanical properties of spherical nanoparticles to improve the biodistribution and effectiveness of NPs, mainly related to bypassing intracellular barriers. Toward this aim, several functionalities have been incorporated in nanocarriers, such as stimuli-responsiveness directed by the unique characteristics of the tumor microenvironment over the healthy cells, as well the attachment of targeting moieties that are overexpressed at the membrane of certain types of cancer cells.…”

Polypeptide-Based Systems: From Synthesis to Application in Drug Delivery

“…Packing density depends on the secondary structure of the polypeptide [306] and cross-linking and affects drug release due to the diffusion of the drugs soluble in the external medium. Dilution of the system to CMC/CAC levels can also affect the stability of the NPs, which in turn favors the release of the drug from nanoformulation [307]. For amphiphilic copolymers, the structure of the hydrophobic component and the hydrophobic-hydrophilic balance affect the CMC/CAC [308].…”

Polypeptide‐PEG Conjugates via Ring Opening Polymerization of l‐Alanine N‐Carboxyanhydride

“…Amphiphilic polypeptide-polymer hybrids have been of interest for biomedical and nonbiological applications [1,2] as materials [3][4][5][6] to achieve biocompatibility, stable 3D structures and responsiveness to external stimuli [7,8] by taking advantage of the versatility of folding and self-assembly of their polypeptide elements. [9][10][11][12][13][14] Specific interactions of the amino acids inside the polypeptide with solvents, [15][16][17][18] together with inter-and intramolecular hydrogen bonding, [19][20][21] hydrophobic, [21,22] and van der Waals forces [21] can induce the formation of secondary structures such as 𝛼-helices [23] or 𝛽-sheets, [24] further ordering the poly(peptides) inside these materials.…”