Polypeptoids have recently emerged as a subject of scientific interest due to their structural resemblance to existing pseudo-peptidic polymers including poly(αpeptide)s, poly(β-peptide)s, poly(2-oxazoline)s, and poly(Nsubstituted acrylamide)s. With demonstrated backbone degradability, biocompatibility, and thermal processability, polypeptoids are potentially useful in a variety of biotechnological applications. Before those applications can be realized, it is important to develop their synthesis and understand their fundamental properties. In this Perspective, we will review recent advances in the synthesis and characterization of polypeptoids and their copolymers as well as the development of polypeptoid-based functional and structured materials. We will conclude by discussing the future prospects for this nascent class of pseudo-peptidic polymers.

Polyethylene glycol (PEG) derivatives were conjugated onto the Cys-34 residue of human serum albumin (HSA) to determine their effects on the solubilization, permeation, and cytotoxic activity of hydrophobic drugs such as paclitaxel (PTX). PEG(C34)HSA conjugates were prepared on a multigram scale by treating native HSA (n-HSA) with 5- or 20-kDa mPEG-maleimide, resulting in up to 77% conversion of the mono-PEGylated adduct. Nanoparticle tracking analysis of PEG(C34)HSA formulations in phosphate buffer revealed an increase in nanosized aggregates relative to n-HSA, both in the absence and presence of PTX. Cell viability studies conducted with MCF-7 breast cancer cells indicated that PTX cytotoxicity was enhanced by PEG(C34)HSA when mixed at 10:1 mole ratios, up to a two-fold increase in potency relative to n-HSA. The PEG(C34)HSA conjugates were also evaluated as PTX carriers across monolayers of HUVEC and hCMEC/D3 cells, and found to have nearly identical permeation profiles as n-HSA.

Traditionally, drug discovery and development research have been primarily focused on the mitigation of disease treatment for the general adult population, often overlooking the medical needs of pediatric patients. While remarkable progress toward the discovery of better medicines has been made, the pharmacological differences between children and adults are often neglected as part of the translation process. In fact, until recently, children have been considered therapeutic orphans due to the lack of significant drug discovery, formulation development, and dosage form design specifically tailored for pediatric patients. Perhaps the least understood is the significant physiological changes that occur during the maturation process from birth to adulthood. It requires careful considerations to achieve age-specific-desired therapeutic outcomes with minimal toxicity. This introduces considerable risk into the preclinical and clinical testing of new medicaments, which until recently, was avoided based on the conventional approach where a demonstration of safe and efficacious use in adults over several years potentially would minimize the chance of adverse juvenile responses. However, the lack of appropriate drug products for children has led to off-label use of adult medicines with potential life-threatening adverse reactions and health complications. Recent developments and future considerations regarding pediatric drug discovery and development using a patient-centric approach in the context of ontogenic biopharmaceutical considerations are discussed below.

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The potential applications of dendrimer-like biopolymers (DLB) as stabilizing excipients for amorphous solid dispersion (ASD) of niclosamide, celecoxib, and resveratrol were evaluated based on (1) the formation and physical stability of the ASD and (2) the permeability and flux of the agents across Caco-2 cell monolayers. The evaluation was made by comparing the performance of prototype phytoglycogen derivatives (DLB1, DLB2, and DLB3) with commonly used polymers such as HPMCAS, PVPVA, and Soluplus®. PXRD was used to confirm the formation of the dispersions and detect crystallinity peaks formed during 2- and 4-week storage at 40°C/75% RH. At concentrations below 2 g/mL, the viability of Caco-2 cells remained above 80% for all DLB samples compared to untreated cells in the MTT assay. Permeability studies revealed a repeating pattern in which an increase in the initial concentration (C) was associated with a concomitant decrease in the apparent permeability (P) which we theorize is due to differences in drug-polymer interactions. Niclosamide-DLB1 dispersion had the lowest flux due to a significant reduction in P. The high increase in the C of celecoxib-DLB2, however, made up for the reduction in the P and produced the highest flux values compared to other polymers. Resveratrol-DLB3 had a 5× reduction in P, but C increased from 25.8 to 176 μg/mL led to a higher flux compared to the crystalline drug without polymer. Collectively, these results provide a "proof-of-concept" basis to demonstrate that DLB excipients have the ability to increase apparent solubility (Sol), most likely due to drug-binding capacity.

During the production process, an editorial error occurred where the label numbering for the first two tables were inadvertently switched. The original article has been corrected.