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Organic Nanocarriers for Brain Drug Delivery
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
Marlene Lúcio, Carla M. Lopes, Eduarda Fernandes, Hugo Gonẹalves, Maria Elisabete C. D. Real Oliveira
Polymers are chemical compounds composed of many repeated monomers and may exist as chains or in branched form and can be from natural origin, like chitosan, alginate and other polysaccharides, or can be synthetic like poly(caprolactone) (PCL), polylactide (PLA), poly(methyl methacrylate) (PMMA), polydimethylsiloxane (PDMS), poly (2-methyl-2-oxazoline) (PMOXA), poly(N-vinylpyrrolidone) (PVP), poly(vinyl alcohol) (PVA) and PEG [112, 113]. Block copolymers are macromolecules which contain multiple adjacent blocks of chemical monomers with different structures or distributed in different sequences [112, 113]. A block copolymer, consisting of two types of monomers is called a diblock copolymer and has amphiphilic properties [112, 113]. Triblock copolymers composed of an inner hydrophobic block attached to outer hydrophilic blocks are also amphiphilic. In aqueous solution, amphiphilic block copolymers, either diblock or triblock, can self-assemble into various supramolecular polymeric structures such as micelles, rods, nanoparticles, or polymersomes (POs) [112, 113]. The final structure of the self-assembly aggregates depends on several parameters such as concentration, molecular weight, geometry of the amphiphilic block copolymers or the ratio of the different blocks [112, 113]. POs are self-assembled vesicles of amphiphilic block copolymers [112–116]. The most common polymer arrangement used in PO formation are diblock(AB) or triblock copolymers (ABA or rarely ABC, where A and C are the hydrophilic blocks and B the hydrophobic block) (Fig. 4.5) [114].
Bioresponsive Nanoparticles
Published in Deepa H. Patel, Bioresponsive Polymers, 2020
Drashti Pathak, Deepa H. Patel
A drug delivery vehicle with pH-sensitive PEG shedding would be especially useful in cancer drug delivery by exploiting the slightly acidic extracellular space of tumors (around pH ~ 6.5). Upon arrival at the tumor site, a correctly tuned pH-sensitive particle would be able to shed its PEG coating, thus enabling it to fuse with the cell membrane and be internalized. Additionally, nanoparticles taken up via the endosomal pathway can be tuned to lose the protective PEG coating upon acidification of the late endosome or early lysosome. Fusing with the endosomal membrane then becomes possible and escape from the endosome can be achieved. The importance of endosomal escape cannot be underestimated, especially for the delivery of degradable payloads like siRNA and other biologics that are typically degraded inside the highly acidic lysosome. Previous research has shown PEG shedding to improve intracellular drug delivery using polymersomes and polyplex micelles. Other PEG shedding molecules that rely on the reduction of disulfide bonds have been used in liposomes and lipoplexes to some success. More recently, Gao et al. Have demonstrated a technique to directly observe PEG shedding using a pair of dye and quencher, confirming the benefits of PEG shedding to intracellular delivery [28, 29].
Medication: Nanoparticles for Imaging and Drug Delivery
Published in Harry F. Tibbals, Medical Nanotechnology and Nanomedicine, 2017
Polymersomes is a term coined for vesicles similar to liposomes, but made with synthetic amphiphilic block copolymers to form the vesicle membranes, rather than lipid or surfactant bilayers. In general, they can be prepared by the methods used in the preparation of liposomes.
Targeted drug delivery strategy: a bridge to the therapy of diabetic kidney disease
Published in Drug Delivery, 2023
Xian Chen, Wenni Dai, Hao Li, Zhe Yan, Zhiwen Liu, Liyu He
The application of polymers has played a significant role in the targeted drug delivery system. Polymeric micelles, polymersomes and nanohydrogels are polymer nanosystems, assembled by polymers with different compositions, structures and molecular weights, and each type of them has its particular identity to attach or encapsulate therapeutic agents (Joglekar and Trewyn, 2013). They can minimize the adverse effects of drugs by the site-specific therapy. Polymeric micelles, with the dimension of 5–100 nm, can prolong the blood circulation time by reducing the clearance of the reticuloendothelial system and decreasing the drug side effects by lower the opsonization (Joglekar and Trewyn, 2013). Polymersome are polymer-based vesicles with amphiphilic copolymers and it can be stimulated by a certain wide wavelength of light in order to increase the drug efficacy and decrease adverse effects (Hernandez Becerra et al., 2022). Nanohydrogel, possessed the characteristic of hydrogel and nanoparticle, is a three-dimensional and cross-linked hydrophilic polymer network, with the diameter of 1–100 nm (Gonçalves et al., 2010). The nanohydrogel can encapsulate the drug through physical attachment, self-assembly and covalent conjugation (Dalwadi and Patel, 2015). Chen L et al. reported a new one-dimensional Cu (II) coordination polymer by using a NNO tridentate (NNO) Schiff base ligand4-fluoro-2-(((2-(methylamino)ethyl)amino)methyl)phenol, which can downregulate the serum amyloid A and TNF-α in STZ induced DKD rats (Pan-Pan Lin and Chen, 2021).
A facile method for anti-cancer drug encapsulation into polymersomes with a core-satellite structure
Published in Drug Delivery, 2022
Hongchao Xu, Weiwei Cui, Zhitao Zong, Yinqiu Tan, Congjun Xu, Jiahui Cao, Ting Lai, Qi Tang, Zhongjuan Wang, Xiaofeng Sui, Cuifeng Wang
Polymersomes, similar to liposomes structure, possess a large watery interior surrounding with a tough bilayer membrane assembled from amphiphilic block polymers, thereby they are also versatile for encapsulation and delivery of both hydrophilic (e.g. proteins, siRNA, DNA) and hydrophobic drug (e.g. paclitaxel, doxorubicin) (Lee & Feijen, 2012; Peters et al., 2014; Rideau et al., 2018). In addition to advantages common to most liposomes-based drug delivery systems, polymersomes displayed many unique features to improve the drug encapsulation and stability over liposomes (LoPresti et al., 2009). Compared with small phospholipid molecules, higher molecular weights polymers are able to form a thicker membrane (in the range of 5–30 nm versus 3–5 nm for liposomes) (Le Meins et al., 2011), which will enhance the mechanical strength and impermeability, therefore, it could not increase the loading capacity of hydrophobic drug, but also decrease the drug leakage from the hydrophobic layer of the membranes (Matoori & Leroux, 2020). Moreover, the tailored polymers are able to control the rate of cargo release by tuning the molecular weights and hydrophobicity. Thicker membranes may result in slower release rates of hydrophobic substrates probably due to higher diffusional distances. Collectively, polymersomes show a superior stability and flexibility which renders them as a suitable candidate for replacing liposomes.
Merits and advances of microfluidics in the pharmaceutical field: design technologies and future prospects
Published in Drug Delivery, 2022
Amr Maged, Reda Abdelbaset, Azza A. Mahmoud, Nermeen A. Elkasabgy
In addition to the enzyme and/or reaction-assisted destabilization for nanoparticles, other stimuli-responsive nanoplatforms were fabricated by applying the microfluidic technique. Polymersomes constructed using the pH-responsive poly([N-(2-hydroxypropyl)]-methacrylamide)-b-poly[2-(diisopropylamino)ethyl methacrylate] block copolymers were of due relevance, especially in pathophysiological states distinguished by alterations in physiological pH values like in case of cancer. Polymersomes could introduce a solution for the delivery of hydrophilic therapeutics like the anticancer drug; doxorubixin. Taking into consideration the low pH value of cancer cells (Glunde et al., 2003) as well as the protonation of the copolymer at pH < 6.5, hence polymersomes were self-assembled at pH > 6.8. Increasing the FRR (aqueous/organic) to 200/100 produced smaller-sized particles (≈60nm) with a small PDI value of 0.06 due to the efficient, rapid mixing being achieved. Drug release data confirmed the disassembly of the polymersomes at pH 5.5, where more than 50% of the drug was released after 4h. On the other hand, at pH 7.4, a sustained release of the drug was observed, where 90% were released after 48h (Albuquerque et al., 2019). This rapid release in an acidic environment exhibited consistent bio-distribution and enhanced cellular uptake of the polymersomes by tumor cells compared to the pure drug, which would guarantee selective cytotoxicity when administered in-vivo.