Temperature Responsive Nanoparticles Based on PEGylated Polyaspartamide Derivatives for Drug Delivery

Abstract

The temperature responsive PEGylated polyaspartamide derivative, denoted as mPEG-PAAHP, was synthesized by the click reaction. FTIR and 1H NMR were adopted to characterize and confirm the chemical structures of the obtained mPEG-PAAHPs. The temperature responsive behavior investigated by transmittance and dynamic light scattering showed that some of the obtained mPEG-PAAHPs exhibited obvious temperature responsiveness and could be used to prepare nanoparticles by quickly heating. Drug paclitaxel can be encapsulated into mPEG-PAAHP based nanoparticles with a high encapsulation efficiency up to 99% (corresponding to a drug loading content of around 9.9%). Dynamic light scattering results showed that the PTX-loaded nanoparticles had a mean size around 80 nm (PDI<0.2) and good stability in PBS with 150 mM ionic strength. In vitro cytotoxicity results showed that mPEG-PAAHP did not show any toxicity to HeLa cells, but the PTX-loaded nanoparticles based on mPEG-PAAHP exhibited obvious anti-cancer activity. Thus, the temperature responsive PEGylated polyaspartamide derivative mPEG-PAAHP may be a promising drug delivery system.

Recent Progress and Advances of Multi-Stimuli-Responsive Dendrimers in Drug Delivery for Cancer Treatment

“…These temperature-dependent changes in solubility involve highly attractive molecules that are used to develop effective thermo-responsive materials [119]. Thermo-sensitive dendrimers could be used in biomedical processes including programmed drug delivery due to the influence of thermotherapy on the temperature of the site of action [120]. Researchers have developed various polymers that undergo transition under fluctuating temperatures such as poly (NiPAM) [79].…”

Polymer-Based Systems for Controlled Release and Targeting of Drugs

“…For use in human applications, the polymer must primarily be biocompatible and non-toxic, and then functionalizable to give the appropriate structural and functional characteristics, such as to make it easily workable, processed, and engineered to obtain the desired system, and to be applied in drug delivery and targeting and/or in diagnosis of diseases.The further possibility of decorating the surface of these polymeric systems (due to the characteristics of the material that constitutes the matrix) with ligands capable of interacting specifically with membrane receptors on cells represents a unique advantage for obtaining targeted drug release to a specific organ, tissue, or cell type [3][4][5][6][7].In this issue, some current examples of design and production of polymeric materials, as well as of searching strategies to modify existing ones, for the making of innovative systems for drug delivery and/or regenerative medicine are collected.In particular, polymeric systems from nanoscale (micelles [8,9], nanoparticles [10,11]) to microscale structures (microparticles [12,13]), and to macrodevices (hydrogels [14] and films [15]) were produced. All the described systems were designed for the controlled and targeted release of conventional or biological drugs, such as paclitaxel [10], or siRNA [11] in the treatment of diseases such as cancer [8] and buccal and skin infections [15,16] by the systemic or local administration route [17]. The starting polymeric materials were chosen from hydrophilic polysaccharides [11,16] to hydrophobic polyesters [9,14], obtaining blended materials or copolymers, which were used to obtain drug delivery systems by using techniques such as microfluidics or hot punching [12,13].Polymeric porous microparticles are currently emerging due to their potential for various applications, such as floating drug delivery systems and inhaled formulations.…”

“…In particular, polymeric systems from nanoscale (micelles [8,9], nanoparticles [10,11]) to microscale structures (microparticles [12,13]), and to macrodevices (hydrogels [14] and films [15]) were produced. All the described systems were designed for the controlled and targeted release of conventional or biological drugs, such as paclitaxel [10], or siRNA [11] in the treatment of diseases such as cancer [8] and buccal and skin infections [15,16] by the systemic or local administration route [17].…”

“…In particular, polymeric systems from nanoscale (micelles [8,9], nanoparticles [10,11]) to microscale structures (microparticles [12,13]), and to macrodevices (hydrogels [14] and films [15]) were produced. All the described systems were designed for the controlled and targeted release of conventional or biological drugs, such as paclitaxel [10], or siRNA [11] in the treatment of diseases such as cancer [8] and buccal and skin infections [15,16] by the systemic or local administration route [17]. The starting polymeric materials were chosen from hydrophilic polysaccharides [11,16] to hydrophobic polyesters [9,14], obtaining blended materials or copolymers, which were used to obtain drug delivery systems by using techniques such as microfluidics or hot punching [12,13].…”

“…Temperature-responsive behavior, as well as the capability to respond to pH or a reducing environment, is achieved for systems ranging from nano-to microdevices to control the release of drugs. Zhang and coworkers described the realization of nanoparticles starting from a temperature-responsive PEGylated polyaspartamide derivative, which were used to carry paclitaxel, showing suitable characteristics that make it a promising drug delivery system [10]. In another paper, biodegradable polymeric micelles based on a polyurethane-polyethylene glycol copolymer with disulfide bonds in the main chain (PEG-PU(SS)-PEG) were produced [8].…”