Tunable pH-Sensitive Poly(β-amino ester)s Synthesized from Primary Amines and Diacrylates for Intracellular Drug Delivery

• Published in: Macromolecular bioscience Vol. 12; no. 10; pp. 1375 - 1383
• Main Authors: Song, Wantong, Tang, Zhaohui, Li, Mingqiang, Lv, Shixian, Yu, Haiyang, Ma, Lili, Zhuang, Xiuli, Huang, Yubin, Chen, Xuesi
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01-10-2012; WILEY‐VCH Verlag; Wiley-VCH
• Subjects: Acrylates - chemistry; Amines - chemistry; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacology; Antineoplastic agents; Applied sciences; Biological and medical sciences; Cell Survival - drug effects; Chemotherapy; Doxorubicin - administration & dosage; Doxorubicin - pharmacology; Drug Carriers - chemical synthesis; Drug Compounding; drug delivery systems; Esters; Exact sciences and technology; Fluorescent Dyes; HeLa Cells; Humans; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; intracellular targeting; Magnetic Resonance Spectroscopy; Medical sciences; Micelles; Organic polymers; Oxazines; Pharmacology. Drug treatments; Physicochemistry of polymers; poly(β-amino ester); Polyethylene Glycols - chemistry; Polymerization; Polymers with particular properties; Preparation, kinetics, thermodynamics, mechanism and catalysts; stimuli-sensitive polymers; Biological properties; Acrylic acid ester; Antineoplastic agent; Ethyleneimine derivative polymer; Biodegradability; Drug carrier; Doxorubicin; Nanoencapsulation; Polyaddition; Micellar critical concentration; Aliphatic polymer; pH; pK; Tumor cell; Release; Amphiphilic polymer; Control release polymer; Ester polymer; Ethylene oxide copolymer; Experimental study; In vitro; Hela cell line; Biological activity; Hydrolysis; Polyelectrolyte; Ester copolymer; Internalization; Preparation; Diblock copolymer; Kinetics; Ethyleneimine derivative copolymer; Aqueous solution; Micellar solution; Acid base titration; Primary amine; Aliphatic copolymer
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.201200122

The pH sensitivity of a series of PbAEs synthesized from primary amines and diacrylates is studied. By changing alkyl groups of the amine monomers, the pKb can be tuned across a broad range (from 3.5 to 7.2). Micelles formed from a PEG‐PbAE block copolymer retain the pH sensitivity of PbAE and can stably load hydrophobic molecules under neutral pH, while quickly dissociate and release their cargoes at pH ≈ 6.0. When the chemotherapy drug DOX is loaded, the micelles show efficient cell proliferation inhibition to HeLa cells and fast intracellular release. Thus, the primary‐amine‐based PbAEs are shown to be promising in the construction of intracellular targeting drug delivery systems.
The pH sensitivity of a series of PbAEs based on primary amines is studied. A PEG‐PolyA3 block copolymer is synthesized from mPEG‐acrylate, 1‐propylamine and 1,4‐butanediol diacrylate. It has a rapid transition at around pH = 6.4. In vitro release and cell experiment studies show that it provides a potential pH‐responsive nanocarrier for intracellular drug delivery.