Single and Multiple Stimuli-Responsive Polymer Particles for Controlled Drug Delivery

Abstract

Polymers that can change their properties in response to an external or internal stimulus have become an interesting platform for drug delivery systems. Polymeric nanoparticles can be used to decrease the toxicity of drugs, improve the circulation of hydrophobic drugs, and increase a drug’s efficacy. Furthermore, polymers that are sensitive to specific stimuli can be used to achieve controlled release of drugs into specific areas of the body. This review discusses the different stimuli that can be used for controlled drug delivery based on internal and external stimuli. Internal stimuli have been defined as events that evoke changes in different characteristics, inside the body, such as changes in pH, redox potential, and temperature. External stimuli have been defined as the use of an external source such as light and ultrasound to implement such changes. Special attention has been paid to the particular chemical structures that need to be incorporated into polymers to achieve the desired stimuli response. A current trend in this field is the incorporation of several stimuli in a single polymer to achieve higher specificity. Therefore, to access the most recent advances in stimuli-responsive polymers, the focus of this review is to combine several stimuli. The combination of different stimuli is discussed along with the chemical structures that can produce it.

Smart Poly(lactide)-b-poly(triethylene glycol methyl ether methacrylate) (PLA-b-PTEGMA) Block Copolymers: One-Pot Synthesis, Temperature Behavior, and Controlled Release of Paclitaxel

“…For this, the PLA molar ratio was varied from 0 to 80 mol% and a PTEGMA homopolymer was synthesized as a control (Table 1). [36]: [9]: [1]:[0.25]:[0.25]. LA (0.34 mg, 2.24 mmol), TEGMA (0.11 mL, 0.85 mmol), CDTP (0.05 g, 0.13 mmol), AIBN (0.006 g, 0.032 mmol), DMAP (0.63 mg, 0.52 mmol) and 0.75 mL of 1,2-dichloroethane were mixed in a dry 10 mL Schlenk flask.…”

“…Stimuli-responsive polymers, also referred to as "smart polymers", are extensively studied in the field of polymer biomaterials [1][2][3]. Basically, after the application of external stimuli, such as changes in temperature, pH, magnetic field, ionic strength, light irradiation, and ultrasound, or by the addition of enzymes, glucose, and reactive oxygen species (ROS), they significantly change their physical or chemical properties [3][4][5][6][7][8][9][10].…”

“…Among these methods, DLS and NMR spectroscopy have advantages, because DLS can easily observe temperature induced transitions in the colloidal level and is largely utilized for comparisons, whereas NMR provides quantitative information on the molecular level related to polymer behavior during LCST phase separation. Moreover, 2D 1 H-1 H NOESY spectra help to clarify the conformational behavior of macromolecules in solution [22,[41][42][43][44][45]; therefore, the combination of DLS and NMR techniques can provide a comprehensive and detailed characterization of phase transitions.…”

“…These copolymers were prepared via the elegant combination of ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization (ROP-RAFT) with different ratios between the hydrophobic and hydrophilic blocks. For the block copolymer characterization, we applied size exclusion chromatography (SEC) and 1 H NMR spectroscopy, whereas 1 H NMR spectroscopy and 2D nuclear Overhauser effect spectroscopy (NOESY) in combination with dynamic light scattering (DLS) was utilized to comprehensively study and characterize the effect of the hydrophobic PLA block on the LCST of the PTEGMA block in aqueous solutions. From the several PLA-b-PTEGMA block copolymers studied, we selected the one which presented LCST transitions at rele-vant temperatures; more specifically, in hyperthermia treatment (38)(39)(40)(41)(42)(43)(44)(45) • C) [46,47], as this can be selectively activated at the tumor sites for drug encapsulation and release of the cargo content.…”

Stimuli‐accelerated polymeric drug delivery systems

“…In the last few years the development of stimuli‐responsive DDS has attracted increasing interest and a multitude of studies and reviews have been published dealing with this topic 28–30 . Numerous reviews discuss stimuli‐responsive DDS under the aspect of a specific medical indication 31–34 .…”