Triblock copolymers for drug delivery

In the last few years there have been new creative methods of preparation of novel hydrophilic polymers and hydrogels that may represent the future in drug delivery applications. The focus in these studies has been the development of polymeric structures with precise molecular architectures. Stupp et al. (1997) synthesized self-assembled triblock copolymer, nanostructures that may have very promising applications in controlled drug delivery. Novel biodegradable polymers, such as polyrotaxanes, have been developed that have particularly exciting molecular assemblies for drug delivery (Ooya and Yui, 1997). 

In the next series of studies, Jeong et al. found compositions of HPL/HPB balanced triblock copolymers, PEG-PLGA-PEG, that exhibit sol-to-gel (lower transition) and gel-to-sol (upper transition) transitions as temperature mono-tonically increases (27). The lower transition is important for drug delivery application because the solution both flows freely at room temperature and becomes a gel at body... 

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. 

Another well-known thermosensitive polymer often used as a micellar component for drug delivery is pluronics (Kabanov et al, 2002 Batrakova and Kabanov, 2008). These triblock copolymers consist of a poly(propylene oxide) middle block flanked by two PEG blocks. They self-assemble into micelles with a PPO block above the LCST of this block. Pluronic micelles loaded with DOX (SP1049C) have reached phase II-III clinical trials, where they have demonstrated slower clearance than the free drug, as well as antitumour activity in advanced MDR adenocarcinoma patients, with acceptable toxicity profile and antitumour activity (Valle et a/., 2011). 

In an effort to adjust the interface properties of polylactide (PLA) nanoparticles used for drug delivery, copolymers were synthesized having a polypeptide block in between PEG and PLA. One copolymer was prepared by polymerization of O-protected l serine-NCA with an amino-terminated PEG. Subsequently, the deprotected serine groups were used to polymerize lactide to produce a comb-like copolymer block. This copolymer was compared with a triblock copolymer PEG-h-poly(alanine)-h-PLA. In this case, the endgroup of the poly(alanine) block was used as initiator [54]. Both types of copolymers form nanoparticles, but the copolymers with the comb-like structure show particularly interesting properties. Zeta-potential measurements indicate that the poly (serine) backbone covers the PLA core. 

Drug Release from PHEMA-l-PIB Networks. Amphiphilic networks due to their distinct microphase separated hydrophobic-hydrophilic domain structure posses potential for biomedical applications. Similar microphase separated materials such as poly(HEMA- -styrene-6-HEMA), poly(HEMA-6-dimethylsiloxane- -HEMA), and poly(HEMA-6-butadiene- -HEMA) triblock copolymers have demonstrated better antithromogenic properties to any of the respective homopolymers (5-S). Amphiphilic networks are speculated to demonstrate better biocompatibility than either PIB or PHEMA because of their hydrophilic-hydrophobic microdomain structure. These unique structures may also be useful as swellable drug delivery matrices for both hydrophilic and lipophilic drugs due to their amphiphilic nature. Preliminary experiments with theophylline as a model for a water soluble drug were conducted to determine the release characteristics of the system. Experiments with lipophilic drugs are the subject of ongoing research. 

Kissel T, Li YX, Unger E. ABA-triblock copolymers from biodegradable polyester A-blocks and hydrophilic poly (ethylene oxide) B-blocks as a candidate for in situ forming hydrogel delivery systems for proteins. Adv. Drug Deliv. Rev. 2002 54 99-134. 

The signiflcant recent advances in both colloidal and polymer chemistries have enabled the successful fabrication of complex, defect-free tianoslruclures following a bottom-up approach [353]. Two recent related examples are mentioned to stress the point. Recently, triblock copolymer with divalent counter-ions in mixed solvents led to the formation of particles with tunable internal structure mimicking lipid anphiphiles for potential use in drug delivery. The mechanism of formation involves either nanophase separation within the triblock copolymer nanoparticle upon addition of water or microemulsion formation similar to that in lipid systems... 

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