Polyamide/Poly(Amino Acid) Polymers for Drug Delivery

Polymers have always played a critical role in the development of novel drug delivery systems by providing the sustained, controlled and targeted release of both hydrophobic and hydrophilic drugs. Among the different polymers, polyamides or poly(amino acid)s exhibit distinct features such as good biocompatibility, slow degradability and flexible physicochemical modification. The degradation rates of poly(amino acid)s are influenced by the hydrophilicity of the amino acids that make up the polymer. Poly(amino acid)s are extensively used in the formulation of chemotherapeutics to achieve selective delivery for an appropriate duration of time in order to lessen the drug-related side effects and increase the anti-tumor efficacy. This review highlights various poly(amino acid) polymers used in drug delivery along with new developments in their utility. A thorough discussion on anticancer agents incorporated into poly(amino acid) micellar systems that are under clinical evaluation is included.

Dual mechanism β-amino acid polymers promoting cell adhesion

Cell adhesion has tremendous impact on the function of culture platforms and implants. Cell-adhesive proteins and peptides have been extensively used for decades to promote cell adhesion, however, their application suffers from their easy enzymatic degradation, difficulty in large-scale preparation and expensiveness. To develop the next-generation cell-adhesive materials, we mimic the cell adhesion functions and mechanisms of RGD and KRSR peptides and design cell-adhesive cationic-hydrophobic amphiphilic β-amino acid polymers that are stable upon proteolysis and easily prepared in large scale at low cost. The optimal polymer strongly promotes cell adhesion, using preosteoblast cell as a model, by following dual mechanisms that are independent of sequence and chirality of the statistic copolymer. Our strategy opens avenues in designing the next-generation cell-adhesive materials and may guide future studies and applications.

Internalization into cancer cells of zwitterionic amino acid polymers via amino acid transporter recognition

We synthesized lysine- and phenylalanine-based zwitterionic amino acid polymers (ZAPs) and evaluated their recognition capability for amino acid transporters (AATs), which are overexpressed on cancer cells as compared with normal...

Utilization of extracellular polymeric substances (EPS) immobilized in epoxy polymer as double ion exchanger biosorbent for removal of chromium from aqueous solution

Cation and industrial pollutant anions are removed from wastewater using organic cation and anion exchange resin. "Extracellular Polymeric Substance" (EPS) from bacterial extraction can accumulate cation and anion elements through biosorption by adsorption mechanism, ion exchange, formation of complex compounds and hydrogen bonds. EPS can be used as an biosorbent and ion exchange bioresin replacing organic resins, because EPS contains organic functional groups that are negatively charged (RCOOH, ROPO3H, ROPO3Na, ROSO3H, ROSO3Na, etc.) cation absorbers and positively charged (ROH, RCNH2HCOOH, etc.) anion absorber. EPS consists of 40-95% polysaccharide compounds, protein 1-60%, nucleic acids 1-10%, lipids 1-10% and the remaining amino acid polymers and other compounds. The tannery industry produces trivalent (Cr+3) chromium pollutants at levels of 15.2 ppm and hexavalent (CrO4-2 or Cr2O7-2) levels of 0.77 ppm which exceeds the standard quality for a total Cr of 0.6 ppm. Cr pollutants are very dangerous for human health. Research had been done on the use of immobilized EPS bioresin in epoxy polymers for chromium binding. EPS was extracted from bacterial activated sludge by centrifugation at 9000 rpm for 20 minutes at 4°C, the filtrate was EPS. The analysis showed EPS content were 16% fat, 12% carbohydrate, and 16% protein. The functional group analysis results with infrared ray spectroscopy (FTIR) showed EPS containing chemical bonds such as -CH, -OH, -NH, and -C=O which proved that EPS extraction contained RCOOH, ROH, and RCNH2HCOOH functional components which were exchanging components cations and anions. Epoxy polymers were prepared by mixing bisphenol A monomers and 1: 1 ratio epichlorohydrin. Immobilized EPS double ion exchange biorecin in epoxy polymers was prepared by mixing 200 mg EPS and 1800 mg epoxy. The binding of chromium ions in the resin was carried out by recirculating the chromium solution through a burette column filled with 2 rams of bioresin at pH 5, 6 and 7. The optimum results gave chromium ion absorption efficiency of 89.20% at pH 5. Column operations could be optimized by varied the amount of bioresin used.

Dewar Heterocycles as Versatile Monomers for Ring-Opening Metathesis Polymerization

We report the utility of readily available heterocycles as precursors to unique ring-opening metathesis polymerization (ROMP) monomers. Photochemical valence isomerization reactions of pyridones, dihydropyridines, and pyrones dearomatize the parent heterocycles to their highly strained Dewar isomers, which readily engage in controlled ROMP reactions using Grubbs catalysts. This strategy is used to access novel polymer backbones that contain strained β-lactam and azetidine cores, which can be further derivatized using post-polymerization chemistries. We demonstrate this through the synthesis of water-soluble β-amino acid polymers and soluble poly(acetylene) derivatives.

Dewar Heterocycles as Versatile Monomers for Ring-Opening Metathesis Polymerization

We report the utility of readily available heterocycles as precursors to unique ring-opening metathesis polymerization (ROMP) monomers. Photochemical valence isomerization reactions of pyridones, dihydropyridines, and pyrones dearomatize the parent heterocycles to their highly strained Dewar isomers, which readily engage in controlled ROMP reactions using Grubbs catalysts. This strategy is used to access novel polymer backbones that contain strained β-lactam and azetidine cores, which can be further derivatized using post-polymerization chemistries. We demonstrate this through the synthesis of water-soluble β-amino acid polymers and soluble poly(acetylene) derivatives.

Physicochemical Foundations of Life that Direct Evolution: Chance and Natural Selection are not Evolutionary Driving Forces

The current framework of evolutionary theory postulates that evolution relies on random mutations generating a diversity of phenotypes on which natural selection acts. This framework was established using a top-down approach as it originated from Darwinism, which is based on observations made of complex multicellular organisms and, then, modified to fit a DNA-centric view. In this article, it is argued that based on a bottom-up approach starting from the physicochemical properties of nucleic and amino acid polymers, we should reject the facts that (i) natural selection plays a dominant role in evolution and (ii) the probability of mutations is independent of the generated phenotype. It is shown that the adaptation of a phenotype to an environment does not correspond to organism fitness, but rather corresponds to maintaining the genome stability and integrity. In a stable environment, the phenotype maintains the stability of its originating genome and both (genome and phenotype) are reproduced identically. In an unstable environment (i.e., corresponding to variations in physicochemical parameters above a physiological range), the phenotype no longer maintains the stability of its originating genome, but instead influences its variations. Indeed, environment- and cellular-dependent physicochemical parameters define the probability of mutations in terms of frequency, nature, and location in a genome. Evolution is non-deterministic because it relies on probabilistic physicochemical rules, and evolution is driven by a bidirectional interplay between genome and phenotype in which the phenotype ensures the stability of its originating genome in a cellular and environmental physicochemical parameter-depending manner.

Efficient synthesis of amino acid polymers for protein stabilization

Poly-l-glutamate exerts substantial protein stabilization during lyophilization by preventing protein aggregation.