Organic Nanocarriers for Brain Drug Delivery
Carla Vitorino, Andreia Jorge, Alberto Pais in Nanoparticles for Brain Drug Delivery, 2021
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].
Pharmacokinetics of Nanocarrier-Mediated Drug and Gene Delivery
Mansoor M. Amiji in Nanotechnology for Cancer Therapy, 2006
Polymeric micelles that are prepared from amphiphilic block or graft copolymers with a spherical core and a shell with a carrier size of 10–100 nm have been undergoing investigation since 1984 and have been studied more actively since 1990.25–27 The term block refers to the linear architecture of the copolymer in which the end of one segment is covalently joined to the head of the other segment to give a diblock AB type (Figure 4.1) or multiple block (ABn) type copolymers. On the other hand, graft copolymers have a comb-like structure with hydrophilic segments attached on the side of the cationic segments. Although the influence of the copolymer architecture on biological activity has not yet been clarified, both block and graft copolymers can form polymeric micelles because of their amphiphilic character. Interactions between the polymer chains that serve as the driving force for micelle formation include hydrophobic, electrostatic, and π–π interactions and hydrogen bonding. Because hydrophobic drugs can be stably trapped in the hydrophobic core of the polymeric micelles and exhibit water-solubility, polymeric micelles are attractive carriers for hydrophobic drugs. Moreover, electrostatic (ionic) interactions involving the hydrophilic surface of polymeric micelles may also be applicable to macromolecules possessing many electrostatic (ionic) charges, e.g., DNA.28
Nanomaterials in Chemotherapy
D. Sakthi Kumar, Aswathy Ravindran Girija in Bionanotechnology in Cancer, 2023
Polymers are large molecular weight substances consisting of repeating monomeric units that are connected via covalent bonds. Nature derived polymers such as polysaccharides (e.g., cellulose, hyaluronic acid, etc.) and synthetic polymers such as poly(glycolic acid), poly(lactic acid), poly(caprolactone), and polydioxanone have become an inevitable component of DDSs. With the advancements in the field of polymers, many efficient methods of polymer synthesis are now available. Careful selection of monomeric motifs can produce polymers having different structures (linear, branched, and dendritic), configurations (copolymers), and properties (hydrophilic and hydrophobic), as shown in Figure 8.7. Some specific type of polymers such as amphiphilic block copolymers is widely utilized for constructing drug carriers in biomedical applications. Hydrophilic/hydrophobic small molecule drugs, nucleic acids, peptides, and proteins can be loaded into polymeric nanocarriers (e.g., micelles and polymersomes), where the designed carriers sustain in the bloodstream and accumulate in a diseased site followed by cellular internalization and drug release [127, 128].
Addressing the challenges to increase the efficiency of translating nanomedicine formulations to patients
Published in Expert Opinion on Drug Discovery, 2021
Sourav Bhattacharjee, David J. Brayden
Polymeric micelles have a hydrophobic core within a hydrophilic corona and offer loading possibilities for both hydrophilic and hydrophobic molecules. The polymeric constituent is usually a di-block or tri-block copolymer, where at least one of the blocks is hydrophilic and forms the outer layer. The hydrophobic block, on the other hand, forms the core, which in turn is stabilized by a range of hydrophobic and ionic bonds or complexation with metal ions. A wide range of polymeric blocks can be used to form cores with different hydrophilicity, such as polypropylene oxide (Pluronics®) [104], polyaspartic acid [105], polylactic acid [106], poly-ε-caprolactone (PCL) [107], and poly(β-benzyl-L-aspartate) [108]. Some of these polymers (e.g., PCL) are biodegradable and can be used to develop sustained-release formulations.
Design and synthesis of mixed micellar system for enhanced anticancer efficacy of Paclitaxel through its co-delivery with Naringin
Published in Drug Development and Industrial Pharmacy, 2019
Tooba Jabri, Muhammad Imran, Aisha Aziz, Komal Rao, Muhammad Kawish, Muhammad Irfan, Muhammad Imran Malik, Shabana Usman Simjee, Muhammad Arfan, Muhammad Raza Shah
Diblock copolymer was synthesized by cationic ring-opening of caprolactone using MeO-PEO5K as macro-initiator. PEO is the most widely used hydrophilic polymer especially for the synthesis of biodegradable amphiphilic block copolymers. On the other hand, polycaprolactone is hydrophobic in nature and biodegradable. Covalent joining of these two blocks gives amphiphilic block copolymers that make micellar structures when dissolved in water. These micelles can be used as a polymeric drug carrier for hydrophobic drugs such as Paclitaxel. Size exclusion chromatographs of macro-initiator and block copolymers are shown in Figure 1. Earlier elution of block copolymer from the macro-initiator confirms the formation of block copolymer. The average molar mass of MeO-PEO5K is 8500 g/mol while for MeO-PEO5K-b-PCL it is 15,000 g/mol. The values are obtained by SEC while using polystyrene calibration. A high elution volume tailing might be due to the formation of some unwanted PCL homopolymers in the sample. Detailed analysis of this aspect has been subject of recent publication [25].
Nanomedicine approaches for sirolimus delivery: a review of pharmaceutical properties and preclinical studies
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Azadeh Haeri, Mahraz Osouli, Fereshteh Bayat, Sonia Alavi, Simin Dadashzadeh
Micelles are spherical or globular colloidal particles made of monolayers with diameters generally less than 100 nm. Traditional micelles, form from an average number (aggregation number) of surfactant monomers, generally have high critical micelle concentration (CMC) and low stability upon dilution. Recently, polymeric micelles, self-assembled NPs prepared from amphiphilic block copolymers in aqueous media, have attracted a great deal of attention due to lower CMC, better thermodynamic stability in physiological solutions, slower rate of dissociation allowing a longer drug retention time, narrow and small size distribution, higher solubilization capacity, controlled drug release and greater accumulation at the target sites mediated by escaping from RES uptake and EPR effect [77]. The block copolymer micelles can be subcategorized into at least two main types: 1) Amphiphilic block copolymer micelles and 2) polyion complex micelles or block ionomer complexes. A-B diblock copolymer, A-B-C triblock copolymer, grafted and hyperbranched polymers are different patterns of micelles formed by arranging these block copolymers [78,79]. Based on a series of studies, drug-loading capacity of micelles can be significantly improved by optimizing chemical structures of inner core for stronger carrier–cargo interaction [77]. Due to numerous advantages of micelles, many researches have been performed on micelles formulation and in vitro as well as in vivo characterization of sirolimus (Table 3).
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