Release from triblock copolymers

Graft copolymers of poloxamers and either poly(acrylic acid) or chitosan change from a sol to a gel at temperature above 37 °C. The appearing gel forms a stable matrix that can retain a drag for its sustained release. The triblock copolymer consisting of polyethylene oxide)-poly(/-lactide)-poly(ethylene oxide) (PEO-PLLA-PEO) is also temperature-sensitive but shows an opposite gellation property. At low... 

The observed release pattern from both types of microspheres lies in the distribution of the protein inside a microsphere, which is associated with the preparation method. In order to see this, FITC (fluorescein isothiocyanate)-insulin incorporated microspheres were observed under a confocal microscope, as shown in Fig. 7. For Msp A, a homogeneous distribution of fluorescence was observed while Msp B exhibited a rather heterogeneous distribution of FITC-insulin. In addition, Msp B shows significant surface fluorescence. These observations are, hence, consistent with the observed initial burst from Msp B and from the constant insulin release from Msp A over a prolonged period of time. It is reported that the constant release of insulin from triblock copolymer hydrogel may be attributed to the hydrophilic/hydrophobic domain structure of the gel. The incorporation of a significant fraction of insulin in the hydrophobic domain may have made possible... 

Figure 11 Facing page) (a) Structural formula of pH-responsive triblock copol3uner consisting of poly[(diisopropylamino)ethyl methaciylate]-6-pol3Kmethacryloyloxyethyl phosphorylcholine)-6-poly[(diisopropylammo)ethyl methacrylate] prepared by ATRP technique, (b) Formation of macroscopic gels of concentrated solution of triblock copolymer, (c) Drug release behavior from triblock copolymer gels at 37°C and at pH 7.4. (From Ref. 72.)...

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. 

In 1997, Kim and coworkers first developed biodegradable IP systems using a triblock copolymer of PEG and PLLA, PEG-b-PLLA-b-PEG, and demonstrated sustained release of drugs from the hydrogel [127]. After this achievement, many kinds of biodegradable amphiphilic block copolymers (including multiblock copolymers) exhibiting temperature-responsive sol-gel transition have been reported [137, 308-318]. In this review, only several recent results are introduced. 

Morlock, M., Kissel, T., Li, Y. X., Koll, H., and Winter, G. (1998), Erythropoietin loaded microspheres prepared from biodegradable LPLG-PEO-LPLG triblock copolymers Protein stabilization and in-vitro release properties, J. Controlled Release, 56,105-115. 

Bittner, B., Witt, C., Mader, K., and Kissel, T. (1999), Degradation and protein release properties of microspheres prepared from biodegradable poly(lactide-co-glycolide) and ABA triblock copolymers Influence of buffer media on polymer erosion and bovine serum albumin release, J. Controlled Release, 60, 297-309. 

Fig. 10 Comparison of mass loss and relative amount of monomeric degradation products released from DXO/CL/DXO triblock copolymer, CL/DXO multiblock copolymer, random crosslinked CL/DXO copolymer and PCL homopolymer after 182 days of hydrolysis in phosphate buffer pH 7.4 and 37 °C. The monomeric products were extracted from the buffer solution with solid-phase extraction and analyzed by GC-MS. All of the copolymers had 60 mol % CL units and 40 mol % DXO imits. Reprinted from [ 160] with permission of American Chemical Society. American Chemical Society (2007)...

Other amphiphilic block copolymers were obtained by porcine pancrease lipase initiation of 5-benzyloxytrimethylene carbonate (BTMC) from mono-hydroxyl poly(vinyl pyrolidone) (PVP-OH) [8], Kaihara reported the enzymatic ROP of trimethylene carbonate from a copolymer of PEG and a cyclic acetal with two terminal hydroxyl groups [9], The latter is a degradable segment and the resulting amphiphilic triblock copolymer was used to form micellar structures for which pH-dependent drug release was successfully shown. 

This ABA-type triblock copolymer was used as a drug release depot for continuous release of hiunan insulin and of glucagons-like peptide-1 (GLP-1). The observation of both reduced initial burst and a constant release of hmnan insulin from ReGel in vitro is due to the domain structure of the gel and to the modification of the association states of insulin by zinc. Animal studies using SD rats were performed to verify the release profile of insuhn from this ABA block copolymer hydrogel. ReGel formrdation maintained insulin release for up to 15 days, which could allow diabetic patients to reduce the number of insulin injections to two per month for basal insulin requirements (31). 

Jeong B, Bae YH, Kim SW. Drug release from hiodegradahle injectable thermosensitive hydrogel of PEG-PLGA-PEG triblock copolymers. J Contr Rel 2000 63 155-163. 

Xu, X. Flores, J.D. McCormick, C.L. Reversible imine shell cross-linked micelles from aqueous RAFT synthesized thermoresponsive triblock copolymers as potential nanocarriers for pH-triggered drug release. Macromolecules 2011,44 (6), 1327-1334. 

---