Temperature Responsive Drug Release

M. Nakayama, T. Okano, T. Miyazaki, F. Kohori, K. Sakai, and M. Yokoyama, Molecular design of biodegradable polymeric micelles for temperature-responsive drug release, / Control Release, 115 (1), 46-56, 2006. 

Martinez-Mdnez and coworkers have reported an innovative strategy to attain temperature-responsive drug release from paraffin-capped MSNPs [159]. An increase in temperature causes the melting of paraffin and triggers drug release. This temperature can be tuned by choosing the appropriate paraffin. 

Zhu, Y, Kaskel, S., Ikoma, T, Hanagata, N. (2009). Magnetic SBA-15/ poly(iV-isopropylaciylamide) composite Preparation, characterization and temperature-responsive drug release property, Microporous Mesoporous Mater, 123,107-112. 

We introduced CDDP into the micelle system where CDDP was complexed with carboxyl groups on PEG-PAsp to form a metal complex micelle (Fig. 3a). The complex spontaneously forms a micelle with a very narrow size distribution having an average diameter of 20 nm [57]. The PEG-PAsp(CDDP) micelles showed an environment responsive drug release behavior. They are stable in distilled water at room temperature, yet in contrast, an exchange between the chloride ion and cisplatin occurred in 150 mM NaCl, resulting in the sustained release of the drug for over 50 h [58]. 

Figure 2 Thermo-responsive drug release behavior from PIPAAm-grafted PIPAAm hydrogels upon step temperature gradient for (a) sodium salicylate, and (b) dextran of MW 9300.

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. 

Thermoresponsive polymeric micelles with PIPAAm block copolymers can be expected to combine passive spatial targeting specificity with a stimuli-responsive targeting mechanism. We have developed LCSTs of PIPAAm chains with preservation of the thermoresponsive properties such as a phase transition rate by copolymerization with hydrophobic or hydrophilic comonomers into PIPAAm main chains. Micellar outer shell chains with the LCSTs adjusted between body temperature and hyperthermic temperature can play a dual role in micelle stabilization at a body temperature due to their hydrophilicity and initiation of drug release by hyperthermia resulting from outer shell structural deformation. Simultaneously, micelle interactions with cells could be enhanced at heated sites due... 

In this study, we demonstrate new pH/temperature-sensitive polymers with transitions resulting from both polymer-polymer and polymer-water interactions and their applications as stimuli-responsive drug carriers [22-23], For this purpose, copolymers of (Ai,Ai-dimethylamino)ethyl methacrylate (DMAEMA) and ethylacrylamide (EAAm) [or acrylamide (AAm)] were prepared and characterized as polymeric drug delivery systems modulated for pulsatile and time release. 

Muscles contract and expand in response to electrical, thermal, and chemical stimuli. Certain polymers, such as synthetic polypeptides, are known to change shape on application of electric current, temperature, and chemical environment. For instance, selected bioelastic smart materials expand in salt solutions and may be used in desalination efforts and as salt concentration sensors. Polypeptides and other polymeric materials are being studied in tissue reconstruction, as adhesive barriers to prevent adhesion growth between surgically operated tissues, and in controlled drug release, where the material is designed to behave in a predetermined matter according to a specific chemical environment. 

Temperature-Responsive IPNs and Their Application to Switches for On-Off Drug Release... 

Fig. 15. Change of drug release rate from IPN-20 in response to step-wise temperature change between 10 °C and 30 CC in distilled water...

In contrast to lipids, polymer chemistry allows various chemical modifications to introduce functionality and make polymers responsible to environmental stimuli (pH, temperature, ions, light, etc.). In biosciences, responsiveness to external stimuli is a crucial factor, especially in drug release and construction of biomaterials. 

Qin et al. [229] produced a thermo-responsive PEO-fe-PNIPAM block copolymer that forms vesicles above the LCST of 32°C. The PEO-b-PNIPAm vesicles are shown to be stable at body temperature and to encapsulate both hydrophilic drugs (e.g., Doxorubicin) and hydrophobic molecules into their membranes (e.g., PKH 26). Temperature-controlled quick release of both types of compounds below 32°C was possible. 

---