Core-shell polymeric micelles

Arimura H, Ohya Y, Ouchi T (2005) Formation of core-shell type biodegradable polymeric micelles from amphiphilic poly(aspartic acid)-Wock-polylactide diblock copolymer. Biomacromolecules 6 720-725... 

Fig. 30 Types of nanocarriers for drug delivery, (a) Polymeric nanoparticles polymeric nanoparticles in which drugs are conjugated to or encapsulated in polymers, (b) Polymeric micelles amphiphilic block copolymers that form nanosized core-shell structures in aqueous solution. The hydrophobic core region serves as a reservoir for hydrophobic drugs, whereas hydrophilic shell region stabilizes the hydrophobic core and renders the polymer water-soluble.

In dilute aqueous solutions, copolymers having hydrophobic and hydrophilic parts may form polymeric micelles, i.e. stable particles with a core-shell structure. The association of the hydrophobic parts of the block copoly-... 

The copolymer-based systems possessing the core-shell structure in solutions are known and studied rather well (see, e.g., [14-16]). These copolymers in aqueous media tend to form polymeric micelles, which are often considered as promising drug delivery nano-vehicles [ 17,18], i.e., these macromolecular systems are not only of scientific, but also of considerable applied significance. Among such systems there are interesting examples, whose properties are very similar to the properties that should be inherent in the protein-like copolymers. All of these macromolecules possess the primary structure of... 

Polymeric micelles with selected chemistries and molecular architecture of block copolymers, such as PIPAAm-CigHgs, PIPAAm-PSt, PIPAAm-PBMA, and PIPAAm-PLA micelles, showed the same LCST and the same thermoreponsive phase transition kinetics as those for PIPAAm irrespective of the hydrophobic segment incorporation. This confirms two points (a) that hydroxyl groups or amino goups of PIPAAm termini completely react with the hydrophobic segment end groups and (b) that the block copolymers form core-shell micellar structures with hydrophobic iimer cores completely isolated from the aqueous phase. 

As with normal hydrocarbon-based surfactants, polymeric micelles have a core-shell structure in aqueous systems (Jones and Leroux, 1999). The shell is responsible for micelle stabilization and interactions with plasma proteins and cell membranes. It usually consists of chains of hydrophilic nonbiodegradable, biocompatible polymers such as PEO. The biodistribution of the carrier is mainly dictated by the nature of the hydrophilic shell (Yokoyama, 1998). PEO forms a dense brush around the micelle core preventing interaction between the micelle and proteins, for example, opsonins, which promote rapid circulatory clearance by the mononuclear phagocyte system (MPS) (Papisov, 1995). Other polymers such as pdty(sopropylacrylamide) (PNIPA) (Cammas etal., 1997 Chung etal., 1999) and poly(alkylacrylicacid) (Chen etal., 1995 Kwon and Kataoka, 1995 Kohorietal., 1998) can impart additional temperature or pH-sensitivity to the micelles, and may eventually be used to confer bioadhesive properties (Inoue et al., 1998). 

The nonionic triblock copolymer polyethylene oxide-polypropylene oxide polyethylene oxide (PEO-PPO-PEO) has been widely used in medicine and has shown low toxicity. Wanka et al. [91] studied aggregation behavior of PEO-PPO-PEO polymeric micelles. In this study, the hydrophobic core of this micellar system consisted of dehydrated poly(oxy-propylene) groups which were surrounded by an outer shell of hydrated poly(oxyethylene) groups. The feasibility of using PEO-PPO PEO micelles as a topical ocular carrier for gene delivery was addressed in an in vivo study on nude mice and albino rabbits [92], Each animal eye was treated with a topical application (10 pL for mouse and 50 pL for rabbit) of 0.08 mg/mL of plasmid and 0.3% (w/v) PEO-PPO-PEO polymeric micelles. After 2 days of three times per day topical delivery, the reporter expression was detected in the treated eyes... 

Important parameters that control the size of micelles are the degree of polymerization of the polymer blocks, NA and NB, and the Flory-Huggins interaction parameter %. The micellar structure is characterized by the core radius Rc, the overall radius Rm, and the distance b between adjacent blocks at the core/shell-interface as shown in Fig. 1. b is often called grafting distance for comparisons to polymer brush models, b2 is the area per chain which compares to the area per head group in case of surfactant micelles. In the case of spherical micelles, the core radius Rc and the area per chain b2 are directly related to the number of polymers per micelles, i.e., the aggregation number Z=4nR2clb2. 

Hydrophilic-hydrophobic diblock copolymers exhibit amphiphilic behavior and form micelles with a core-shell architecture. These polymeric carriers have been used to solubilize hydrophobic drugs, to increase blood circulation time, to obtain favorable biodistribution, and to lower interactions with the reticuloen-... 

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