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In this paper, a doxorubicin delivery system is reported based on a pH-responsive zwitterionic polypeptide derivative. To improve the anti-protein-fouling capacity, the poly(amino acid) was modified by grafting short-chain zwitterions via aminolysis reaction of polysuccinimide with l-lysine. As a result, both positively and negatively charged moieties were introduced onto the same side chain in a simultaneous fashion, providing a nano-scale homogenous mixture of balanced charges. The zwitterionic side chains serve as hydrophilic segments in the copolymer and feature excellent resistance to nonspecific protein adsorption. Doxorubicin was chemically grafted onto the poly(amino acid) moiety through acid-labile hydrazone linkages, providing removable hydrophobic segments and driving the polymer self-assembly. Free doxorubicin could be encapsulated into the self-assembled micelles via hydrophobic interactions and molecular π-π stacking. The results obtained show that the drug loaded nanoparticles exhibit excellent stabilities in protein solutions at pH=7.4 and significantly enhanced drug release characteristics under acidic conditions. The cytotoxicity characteristics of the zwitterionic copolymer and drug-loaded nanoparticles at different pH values were investigated in vitro and feature an excellent biocompatibility and anti-cancer activity, respectively., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In an effort to prove the inherent side effects of doxorubicin (DOX) and potentially revoke the effects of drug resistance exhibited by cancer cells, we have designed a multifunctional DOX-delivery nano-carrier system able to encapsulate the drug resistance reversal agent Verapamil HCl (VRP·HCl). Hydrophilic short-chain polyethylene glycol (i.e., mPEG) was covalently linked to hydrophobic DOX and a benzoic imine linkage was used to form a linear amphiphilic PEGylated prodrug, namely mPEG-b-DOX. In aqueous solution, the amphiphilic PEG-b-DOX is able to self-assemble to form stable nanoparticles with a DOX loading content of approximately 40 wt% and a diameter of ∼ 143 nm. The resulting nanoparticles can simultaneously serve as an anticancer drug conjugate and as a drug carrier system. Here, the hydrophilic VRP could be encapsulated into the nano-carriers via a conventional dialysis method. The loading efficiency in mPEG-b-DOX nano-carrier was determined to be 53.97% and the loading content was found to be 7.71 wt%. The VRP-loaded nano-carriers grew slightly in size, to a diameter of ∼ 177 nm. We found that the release of DOX and VRP was much faster at a lower pH value. The biological activity of the nano-carriers were evaluated in vitro and compared with the DOX-loaded system. In doing so we found that the VRP-loaded nano-carrier features a much higher antitumor activity. Furthermore, the combined-system exhibits a significantly enhanced cytotoxicity with an elevated apoptosis rate observed for MCF-7/ADR used as a cell line in this in vitro study. This combinatory system and promising candidate for applications involving DOX chemotherapy proved to be easy to prepare and could be characterized in terms of biocompatibility, biodegradability, loading capacity, pH responsiveness and reversal of drug resistance., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A pH-responsive polymeric micelle based on poly(aspartamide) derivative was explored as an efficient acid-triggered anticancer drug delivery system. Poly(α,β-l-asparthydrazide) (PAHy) was prepared by aminolysis reaction of polysuccinimide with hydrazine hydrate. Poly(ethylene glycol) and aliphatic chain (C18) were conjugated onto PAHy to afford an amphiphilic copolymer with acid-liable hydrazone bonds. The structure of the resulting copolymer and its self-assembled micelles were confirmed by (1) H NMR, FTIR, DLS, and TEM. Furthermore, doxorubicin (DOX) was loaded into the polymeric micelles via the hydrophobic interaction between the C18 group and DOX molecules, and the π-π staking between the hydrazone conjugated DOX and free DOX molecules. Results showed that the DOX loaded nanoparticle (NP) was relatively stable under physiological conditions, while the DOX was quickly released in response to acidity due to the shedding of mPEG shells and dissociating of C18 segments because of the pH-cleavage of intermediate hydrazone bonds. In addition, the DOX loaded micelles presented a high cytotoxic activity against tumor cells in vitro. This pH responsive NP has appeared highly promising for the targeted intracellular delivery of hydrophobic chemotherapeutics in cancer therapy., (© 2015 Wiley Periodicals, Inc.)

A series of linear amphiphilic poly(ether-urethane)s with alternative hydrophilic/hydrophobic segments based on PEG-diisocyanates and aliphatic diols is developed. The molecular structures of the copolymers were confirmed with nuclear magnetic resonance, Fourier transform infrared spectra and gel permeation chromatography. Nanoparticles prepared by self-assembly of the resulting copolymers show sharp temperature-responsive phase transition. The phase transition temperature could be easily modulated by the length of hydrophilic or hydrophobic segments of the polymer. The mechanism of the temperature-responsive behaviour is discussed. In the presence of these obtained poly(ether-urethane)s, doxorubicin (DOX) could be dispersed into aqueous solution. The ratio of DOX release from polymeric particles increased sharply above the phase transition temperature, while the release was suppressed below the phase transition temperature. A controlled drug release can be achieved by changing the environmental temperature. The easy-prepared polymeric nanoparticles, with features of biocompatibility, biodegradability and tail-made temperature responsiveness, are a kind of promising carriers for temperature-controllable drug release.

Amino poly(glycerol methacrylate)s (PGOHMAs) were synthesized from linear or star-shaped poly(glycidyl methacrylate)s (PGMA)s via ring opening reactions with 1,2-ethanediamine, 1,4-butanediamine and diethylenetriamine, respectively. The resulting cationic polymers were employed to form polyelectrolyte complexes (PECs) with insulin. Parameters influencing complex formation were investigated by dynamic light scattering (DLS). PECs in the size range of 100-200 nm were obtained under optimal conditions, i.e., the pH value of PECs was 5.58-6.27, the concentration of NaCl was 0.02 mol/L, and insulin-polymer weight ratio was 0.8. The insulin association efficiency (AE) of current system increased with zeta potentials of PECs. Circular dichroism (CD) analysis corroborated that the structure of insulin in the PEC nanoparticles was preserved after lyophilization. Fourier transform infrared (FT-IR) and X-ray diffraction (XRD) experiments demonstrated that weak physical interactions between insulin and amino PGOHMAs play an important role in the formation of PECs. The release of insulin depends on both structure and architecture of amino PGOHMAs. These PECs would be potentially useful for mucosal administration., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Synergistic drug therapy has proven to be an effective strategy for various disease states. An injectable nano-hydrogel has been successfully prepared by random copolymerization of N-isopropylacrylamide (NIPAM) and acrylic functionalized nucleobase (adenine) for synergistic drug delivery. Different from ordinary polymeric hydrogels, the prepared injectable hydrogel showed a special phase-separated structure, combining nano-particles and macro-hydrogels, and potentially became useful as a dual drug carrier with a sequential release of different drug species. In addition, the obtained nanogels demonstrated fluorescence characteristics in a broad concentration range, without emission quenching at high concentrations. This feature is particularly important for possible visualization and imaging purposes. The studied material may represent a suitable candidate for fluorescent biological probes and dual drug delivery systems with intelligent responsiveness. [ABSTRACT FROM AUTHOR]