Micelles drug delivery applications

A final biomedical use for polyphosphazenes is as components in microspheres, vesicles, and micelles for use in drug-delivery applications. Microspheres are pseudo-spherical constructs that range in size from 1 to 600 microns. Vesicles (lipozomes) are hollow, water-filled bilayer spheres with diameters that range from 0.03 tolO microns. Micelles typically have diameters near 1 micron (100 nanometers). Idealized representations of these three structures are shown in Figure 3.23, together with the location of trapped drug molecules. 

The aim of this chapter is to give a brief selective overview of typical biomedical areas where cationic polymers can be employed. The use of cationic polymers in tissue engineering is a high priority topic in this chapter and several aspects on this phenomenon are given related to this is the potential of cationic hydrogels for medical and pharmaceutical applications. The importance of cationic polymers and copolymers as non-viral vectors in gene therapy is described, as well as how micelles and vesicles based on cationic polypeptides can form nanostructures by self-assembly. The potential of cationic polymers for drug delivery applications is also elucidated. 

Another attempt to incorporate PNIPAM segments into the ABA architecture has been completed through the RAFT mechanism. PDMA-PNIPAM-PDMA copolymers were synthesized at room temperature in water using a novel water-soluble trithiocarbonate RAFT agent. Thermo sensitive reversible micelles are obtained at temperatures above the LCST of PNIPAM by hydrophobic association showing that these triblocks are promising candidates for drug delivery applications. 

Various other combinations of hydrophobic-hydrophilic blocks are of interest as micellar microcontainers in drug-delivery applications, such poly(DL lactide)-poly(N-vinyl-2 pyrro-lidone) [301], poly(lactide)-depsipeptide [302], poly(malic acid)-poly(malic ester) [303], dendrimer unimolecular micelles [304], etc. 

Kataoka and co-workers and the Eisenberg group pioneered the use of polymeric micelles in drug delivery applications [93-96]. The Kataoka group prepared copolymer micelles with the concept that these should exhibit properties similar to those of natural drug delivery systems - that is viruses. However, unlike viruses, multi-component micelles coated with polyethylene glycol are fully biocompatible and cannot be identified inside the body as foreign substances. It was found that therapeutic molecules could be inserted, such... 

For drug delivery applications, cross-linking through disulfides can be useful for increasing the stability of polymeric micelles or other types of nanoparticles in vivo. Wang et al. (2011) synthesized disulfide bridged block copolymer of PCL and poly(ethylethylene phosphate) (PCL-SS-PEEP), which self-assembled into 90 nm micellar structures. When these micelles were loaded with DOX, more drug accumulation and retention was observed in MDR cells compared to normal block copolymers, and rapid... 

Zhang, Q., Ko, N.R., Oh, J.K. Recent advances in stimuh-responsive degradable block copolymer micelles synthesis and controlled drug delivery applications. Chem. Conunun. 48(61), 7542-7552 (2012)... 

ELP-based triblock copolypeptides have also been used to produce stimulus-responsive micelles, and Chaikof and coworkers envisioned the possible application of these micelles as controlled drug delivery vehicles. These amphiphilic triblock copolymers were constructed from two identical hydrophobic ELP endblocks and a hydrophilic ELP midblock. Below the transition temperature, loose and monodispersed micelles were formed that reversibly contracted upon heating, leading to more compact micelles with a reduced size [90]. 

As with micelle-facilitated dissolution, emulsion-facilitated dissolution has gained renewed interest due to its application to water-insoluble drug delivery and enhanced absorption. Over the years, emulsion systems have been developed and used to either model the in vivo dissolution process or mimic the intestinal surfactant system to enhance drug delivery of poorly soluble compounds [54-66], Emulsions have also been used as vehicles for drug delivery, e.g., to protect... 

Gaucher G, Dufresne MH, Sant VP et al (2005) Block copolymer micelles preparation, characterization and application in drug delivery. J Control Release 109 169-188... 

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