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Nanomaterials in Chemotherapy
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
P. K. Hashim, Anjaneyulu Dirisala
In polymer–drug conjugates (pendant chain systems), drugs are covalently conjugated to the polymer backbone via a physiologically labile (hydrolytically or enzymatically degradable or exchangeable or stimuli-responsive) spacers (Figure 8.5G), and the drug release is tailored by the rate of scission of the bonds [58, 59].
Investigational Nanomedicines in 2016: A Review of Nanotherapeutics Currently Undergoing Clinical Trials *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Joseph M. Caster, Artish N. Patel, Tian Zhang, Andrew Wang
The conjugation of polymers to drugs can impart many of the physical advantages described above. Importantly, it increases the mean size of the active agent which improves passive tumor targeting. Several polymer-drug conjugates are currently in clinical trials.
Nanocarriers as an Emerging Platform for Cancer Therapy
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Dan Peer, Jeffrey M. Karp, Seungpyo Hong, Omid C. Farokhzad, Rimona Margalit, Robert Langer
To date, at least 12 polymer–drug conjugates have entered Phase I and II clinical trials (Table 2.2 and Fig. 2.3a) and are especially useful for targeting blood vessels in tumours. Examples include anti-endothelial immunoconjugates, fusion proteins [57–59], and caplostatin, the first polymer-angiogenesis inhibitor conjugates [60]. Polymers that are chemically conjugated with drugs are often considered new chemical entities (NCEs) owing to a distinct pharmacokinetic profile from that of the parent drug. Despite the variety of novel drug targets and sophisticated chemistries available, only four drugs (doxorubicin, camptothecin, paclitaxel, and platinate) and four polymers (N-(2-hydroxylpropyl)methacrylamide (HPMA) copolymer, poly-L-glutamic acid, poly(ethylene glycol) (PEG), and Dextran) have been repeatedly used to develop polymer–drug conjugates [3, 61].
Polymer drug conjugates containing memantine, tacrine and cinnamic acid: promising nanotherapeutics for the treatment of Alzheimer’s disease
Published in Journal of Microencapsulation, 2023
Tobeka Naki, William Morwa Reagile Matshe, Mohammed Olusegun Balogun, Suprakas Sinha Ray, Samuel Ayodele Egieyeh, Blessing Atim Aderibigbe
Michael addition polymerisation is a flexible synthetic approach useful for generating polymers ranging from linear to hyperbranched polymers (Sun et al. 2017). Aqueous Michael’s addition polymerisation technique was used to synthesise the polymer-drug conjugates in this study. The conjugates are prepared in water in a one-pot process and are characterised by linear architectures. The reaction involves a nucleophilic addition of a nucleophile to an α, β-unsaturated carbonyl compound. Under mild reaction conditions, the reaction is useful for forming C–C bonds. The advantages of Michael addition reactions are high conversions, the capability to accommodate high functional groups and favourable reaction rates (Aderibigbe et al. 2020). The aza Michael polyaddition of prim-monoamines or bis-sec-amines with bis-acrylamides yields a synthetic polymer called linear polyamidoamines (PAAs) (Marcioni et al. 2021). PAAs are polymeric carriers with high structural flexibility. They can be engineered to be biodegradable and biocompatible, and are mostly highly water-soluble and hydrophilic. Their capability to hydrolytically degrade in aqueous systems arise from the amide bond on their backbone. Most of them have demonstrated promising antiviral activity, useful as sensor constituents, heparin complexing agents, heavy metal ion complexing agents, transfection promoters and drug delivery systems (Coué and Engbersen 2011, Marcioni et al. 2021). Polymer-drug conjugates are nanoscale systems in which a drug molecule is covalently attached to a polymer backbone (Duro-Castano et al.2015).
PEGylated drug delivery systems in the pharmaceutical field: past, present and future perspective
Published in Drug Development and Industrial Pharmacy, 2022
Eva Sanchez Armengol, Alexander Unterweger, Flavia Laffleur
Polymer-drug conjugates are one of the central components in nowadays drug delivery field, targeting lower immunogenicity, enhancing solubility, improving reliability, controlling liberation profiles and enhancing the bioavailability of active compounds [1]. Although there are many polymers available on the market, polyethylene glycol (PEG) is commonly used due to its capacity of combining with proteins. Moreover, PEG presents many advantages, from elevated bioavailability, controlled release, improved physicochemical properties to relocating of the plasma half-life. Thus, PEG represents a gold standard as a polymer to conjugate with drugs. However, there is one main drawback of PEG seen in the low biodegradability. For this reason, a modification in the structure of PEG to allow its fragmentation is of great interest [2–4].
Natural polymeric nanocarriers in malignant glioma drug delivery and targeting
Published in Journal of Drug Targeting, 2021
Yuan Gao, Rui Wang, Lixia Zhao, Anchang Liu
Dextran is a common unbranched polysaccharide and is widely explored as raw materials of medical products due to its excellent biodegradability, non-antigenicity, biocompatibility and non-immunogenicity. Its main chain is composed of monomer ɑ-D-glucose. Generally, ɑ-(1→6) glycosidic bond is the core bonding bond while ɑ-(1→4) or ɑ-(1→3) glycosidic bonds exist as the initial end of the branch chain [75]. The structure of the dextran is shown in Figure 4. Polymer–drug conjugates refer to the combination of drugs and polymer-carriers via different chemical bonds. Dextran-based polymer–drug conjugates are typically linked by ester or amide bond, which could affect hydrolysis or enzymolysis in vivo, and enhance the stability and release kinetics of drugs [76]. Han et al. [88] designed an RVG peptide liganded multi-targeting micelles (RVG-Dex-PTX) bypass the BBB, and then reach brain glioma. Carboxylated dextran was first made through a reaction between dextran and succinic anhydride conjugated with PTX via ester bond later. Results showed better anticancer activity in vivo and in vitro than monomer drugs. Li et al. [89] facilely synthesised a polysaccharide-di-drugs conjugate Dex-g-(DOX + BTZ)/cRGD via the one-pot Schiff base reaction between oxidised dextran (Dex-CHO) and c(RGD) and DOX, and boronic esterification between Dex-CHO and bortezomib (BTZ). The formed polysaccharide conjugate could be self-assembled into micelle with a diameter at around 80 nm in an aqueous condition and released DOX and BTZ simultaneously triggered by the acidic condition.