Amphiphilic Star Polypept(o)ides as Nanomeric Vectors in Mucosal Drug Delivery

Skoulas, Dimitrios; Stuettgen, Vivien; Gaul, Rachel; Cryan, Sally‐Ann; Brayden, David J.; Heise, Andreas

doi:10.1021/acs.biomac.0c00381

Cited by 20 publications

(20 citation statements)

References 61 publications

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“…Dendrimers, highly branched, yet precise and discrete macromolecules offer a broad range of functionality and are being used increasingly as either drug themselves (e.g., Vivagel, Starpharma), gene delivery vehicles or as scaffolds for creating larger star polymers. [ 181 ] They provide a means of overcoming polymer heterogeneity seen with other architectures. Originally their branching units, or generations, radiating from an initiating core unit either through divergent or convergent methodologies, were added stepwise, affording high synthetic precision and low dispersity.…”

Section: Developabilitymentioning

confidence: 99%

Highway to Success—Developing Advanced Polymer Therapeutics

England

Akhtar

2021

Advanced Therapeutics

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Polymer therapeutics are advancing as an important class of drugs. Polymers have already demonstrated their value in extending the half‐life of proteins. They show great potential as delivery systems for improving the therapeutic index of drugs, via biophysical targeting and more recently with more precision targeting. They are also important for intracellular delivery of nucleic acid based drugs. The same frameworks that have been successfully applied to improve the small molecule drug development can be adopted. This approach together with improved pathophysiological disease knowledge and critical developability considerations, imperative given the size and complexity of polymer therapeutics, provides a structured framework that should improve their clinical translation and exploit their functionality and potential. Progress in understanding the right target, gaining the right tissue and cell exposure, ensuring the right safety, selecting the right patient population is discussed. The right commercial considerations are outlined and the need for a multi‐disciplinary approach is emphasized. Crucial developability factors together with scientific and technical advancements to enable pharmaceutical development of a quality robust product are addressed. It is argued that by applying this structured approach to their design and development, polymer therapeutics will continue to grow and develop as important next generation medicines.

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Section: Developabilitymentioning

confidence: 99%

Highway to Success—Developing Advanced Polymer Therapeutics

England

Akhtar

2021

Advanced Therapeutics

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“…[58] Barz and co-workers and Heise and co-workers synthesized various star-like PAAs by multifunctional initiators. [59,60] The star-like PAAs served as nanocarriers in mucosal drug delivery [61] and delivery of small interfering RNAs (siRNAs) [59] and DNAs. [62,63] Vicent and co-workers reported star-shaped polyglutamates, which self-assembled softly into nanostructures with applicability in drug delivery.…”

Section: Advances In Polymerizations Of Ncasmentioning

confidence: 99%

An Inspection into Multifarious Ways to Synthesize Poly(Amino Acid)s

Zheng

Bai

Tao

et al. 2021

Macromol. Rapid Commun.

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Poly(𝜶-amino acid)s (PAAs) attract growing attention due to their essential role in the application as biomaterials. To synthesize PAAs with desired structures and properties, scientists have developed various synthetic techniques with respective advantages. Here, different approaches to preparing PAAs are inspected. Basic features and recent progresses of these methods are summarized, including polymerizations of amino acid N-carboxyanhydrides (NCAs), amino acid N-thiocarboxyanhydrides (NTAs), and N-phenoxycarbonyl amino acids (NPCs), as well as other synthetic routes. NCA is the most classical monomer to prepare PAAs with high molecular weights (MWs). NTA polymerizations are promising alternative pathways to produce PAAs, which can tolerate nucleophiles including alcohols, mercaptans, carboxyl acids, and water. By various techniques including choosing appropriate solvents or using organic acids as promoters, NTAs polymerize to produce polypeptoids and polypeptides with narrow dispersities and designed MWs up to 55.0 and 57.0 kg mol −1 , respectively. NPC polymerizations are phosgene-free ways to synthesize polypeptides and polypeptoids. For the future prospects, detail investigations into polymerization mechanisms of NTA and NPC are expected. The synthesis of PAAs with designed topologies and assembly structures is another intriguing topic. The advantages and unsettled problems in various synthetic ways are discussed for readers to choose appropriate approaches for PAAs.

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“…In contrast to polypeptides, polypeptoids, with the branching on the nitrogen atom instead of the α-position, do not show classical secondary structure formation as no hydrogen bond donor is present if no specific modification was introduced. − As such, polysarcosine (pSar, poly( N -methyl glycine)) adopts random coil conformation in aqueous solution, is highly water-soluble (A2 parameter of 3.50·10 –6 mol·dm 3 ·g –2 for pSar 185 at 20 °C), and can be considered a stealth-like material. − For medical applications, polysarcosine is considered the most promising alternative to polyethylene glycol since substantial advantages like reduced proinflammatory cytokine secretion and reduced complement activation as well as evasion of the accelerated blood clearance (ABC) phenomenon have been reported. ,− The combination of polypeptides and polysarcosine in polypept(o)ides thus represent a promising class of biobased or even endogenous materials. ,, While the concept of polypept(o)ides extends from linear block copolymers to cylindrical bottle-brush and star-shaped polymers including miktoarm stars, ,− polysarcosine itself has further been successfully combined with various other classes of synthetic polymers. ,, …”

Section: Introductionmentioning

confidence: 99%

Secondary Structure-Driven Self-Assembly of Thiol-Reactive Polypept(o)ides

et al. 2021

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Secondary structure formation differentiates polypeptides from most of the other synthetic polymers, and the transitions from random coils to rod-like α-helices or β-sheets represent an additional parameter to direct self-assembly and the morphology of nanostructures. We investigated the influence of distinct secondary structures on the self-assembly of reactive amphiphilic polypept(o)ides. The individual morphologies can be preserved by core cross-linking via chemoselective disulfide bond formation. A series of thiol-responsive copolymers of racemic polysarcosine- block -poly( S -ethylsulfonyl- dl -cysteine) (pSar- b -p( dl )Cys), enantiopure polysarcosine- block -poly( S -ethylsulfonyl- l -cysteine) (pSar- b -p( l )Cys), and polysarcosine- block -poly( S -ethylsulfonyl- l -homocysteine) (pSar- b -p( l )Hcy) was prepared by N -carboxyanhydride polymerization. The secondary structure of the peptide segment varies from α-helices (pSar- b -p( l )Hcy) to antiparallel β-sheets (pSar- b -p( l )Cys) and disrupted β-sheets (pSar- b -p( dl )Cys). When subjected to nanoprecipitation, copolymers with antiparallel β-sheets display the strongest tendency to self-assemble, whereas disrupted β-sheets hardly induce aggregation. This translates to worm-like micelles, solely spherical micelles, or ellipsoidal structures, as analyzed by atomic force microscopy and cryogenic transmission electron microscopy, which underlines the potential of secondary structure-driven self-assembly of synthetic polypeptides.

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Amphiphilic Star Polypept(o)ides as Nanomeric Vectors in Mucosal Drug Delivery

Cited by 20 publications

References 61 publications

Highway to Success—Developing Advanced Polymer Therapeutics

Highway to Success—Developing Advanced Polymer Therapeutics

An Inspection into Multifarious Ways to Synthesize Poly(Amino Acid)s

Secondary Structure-Driven Self-Assembly of Thiol-Reactive Polypept(o)ides

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