Amphiphilic sugar poly(orthoesters) as pH-responsive nanoscopic assemblies for acidity-enhanced drug delivery and cell killing

Abstract

A sugar poly(orthoester)-based drug delivery system was constructed to achieve acidity-enhanced drug delivery and cell killing.

Poly(amino acid)-polyester graft copolymer nanoparticles for the acid-mediated release of doxorubicin

“…5 In addition, the polymer restricts undesired and non-selective drug-receptor interactions, an imperative requirement for the delivery of toxic anti-cancer drugs to minimise the extremely unpleasant side effects that are associated with prolonged chemotherapy. 6 In particular, polyanhydrides, 8 poly(amino acid)s, 9 poly(alkyl cyanoacrylate)s 10 and polyorthoesters 11 have been highlighted as promising drug delivery vehicles. Such polymers are designed undergo programmed hydrolysis at a target side to liberate the therapeutic agent following polymer degradation.…”

A Synthetic Bioinspired Carbohydrate Polymer with Mucoadhesive Properties

“…Alternatively, purely synthetic routes to such polymers are equally challenging as many of the desirable chemical characteristics of polysaccharides for biological applications (pyranose backbone, numerous hydroxyl functionalities, defined stereochemistry) necessitate rigorous and lengthy synthesis to prepare even oligosaccharides (<10 repeating units) . Consequently, efforts are ongoing to develop carbohydrate‐inspired polymers with non O ‐glycosidic linkages such as amide, carbonate, and phosphodiester linkages. These novel materials, however, fail to recapitulate all of the key physicochemical and biointerfacial properties of polysaccharides.…”

“…These novel materials, however, fail to recapitulate all of the key physicochemical and biointerfacial properties of polysaccharides. Indeed, previously reported carbohydrate‐inspired polymers largely suffer from poor aqueous solubility to complete insolubility, a lack of deprotected functional groups important for biological interaction (e.g., hydroxyls, amines, phosphates, carboxylates), and/or rapid degradation in acidic or basic pH . Moreover, the rigid pyranose ring backbone absent in some carbohydrate‐mimic and glyco‐polymers plays an essential role in polymer structure and resulting macroscale properties .…”

Well‐Defined Poly(Ortho Ester Amides) for Potential Drug Carriers: Probing the Effect of Extra‐ and Intracellular Drug Release on Chemotherapeutic Efficacy

“…Moreover, the hydrolysis rate of ortho ester may improve 1–4 orders of magnitude in response to mildly acidic condition, compared to that of such acid‐labile linkages as acetal, ketal, and hydrazine. So, the ultra‐pH sensitivity to extracellular pH (≈6.5) may be achieved by optimizing the hydrophilicity of these ortho ester‐based polymeric carriers . Herein, different pH‐sensitive drug carriers (poly(ortho ester malonamides) (POEAd‐C3) and poly(ortho ester adipamides) (POEAd‐C6)) could be realized by the tunable polycondensation between ortho esters and different hydrophobic aliphatic chain lengths carboxylated by succinic anhydride (Scheme ).…”