Synthesis and Characterization of Injectable, Thermally and Chemically Gelable, Amphiphilic Poly(N-isopropylacrylamide)-Based Macromers

Abstract

In this study, we synthesized and characterized a series of macromers based on poly( N-isopropylacrylamide) that undergo thermally induced physical gelation and, following chemical modification, can be chemically cross-linked. Macromers with number average molecular weights typically ranging from 2000-3500 Da were synthesized via free radical polymerization from, in addition to N-isopropylacrylamide, pentaerythritol diacrylate monostearate, a bifunctional monomer containing a long hydrophobic chain, acrylamide, a hydrophilic monomer, and hydroxyethyl acrylate, a hydrophilic monomer used to provide hydroxyl groups for further chemical modification. Results indicated that the hydrophobic-hydrophilic balance achieved by varying the relative concentrations of comonomers used during synthesis was an important parameter in controlling the transition temperature of the macromers in solution and stability of the resultant gels. Storage moduli of the macromers increased over 4 orders of magnitude once gelation occurred above the transition temperature. Furthermore, chemical cross-linking of these macromers resulted in gels with increased stability compared to uncross-linked controls. These results demonstrate the feasibility of synthesizing poly( N-isopropylacrylamide)-based macromers that undergo tandem gelation and establish key criteria relating to the transition temperature and stability of these materials. The data suggest that these materials may be attractive substrates for tissue engineering and cellular delivery applications as the combination of mechanistically independent gelation techniques used in tandem may offer superior materials with regard to gelation kinetics and stability.

Thermoresponsive Polymers for Biomedical Applications

“…PNIPAAm has a lower critical solution temperature, LCST of around 32 °C, a very useful temperature for biomedical applications since it is close to the body temperature (37 °C). Adjustment of the LCST of PNIPAAm has been achieved by copolymerizing with hydrophilic or hydrophobic monomers rendering the overall hydrophilicity of the polymer higher or lower respectively [3,5,6,15]. Other polymers with thermoresponsive properties include poly(N,N-diethylacrylamide) (PDEAAm) with an LCST over the range of 25 to 32 °C, poly(N-vinlycaprolactam) (PVCL) [7,8,16] with an LCST between 25 and 35 °C, poly [2-(dimethylamino)ethyl methacrylate] (PDMAEMA) [17][18][19][20][21][22] with an LCST of around 50 °C [21] and poly(ethylene glycol) (PEG), also called poly(ethylene oxide) (PEO) whose LCST is around 85 °C [23][24][25][26].…”

“…"Smart" materials, i.e., materials that have the ability to respond to external stimuli, represent one of the most exciting and immerging class of materials [1][2][3][4][5][6][7][8][9]. One of the main groups of "smart" materials is based on polymers because they are cheaper and more easily tailored than metals or ceramics.…”

“…One of the main groups of "smart" materials is based on polymers because they are cheaper and more easily tailored than metals or ceramics. These polymeric "smart" materials can respond to stimuli such as pH, temperature, ionic strength, electric or magnetic field, light and/or chemical and biological stimuli and consequently have a wide range of applications that include sensors, drug delivery, gene delivery and tissue engineering [1][2][3][4][5][6][7][8][9][10].…”

Temperature-Sensitive Poly(vinyl alcohol)/Poly(methacrylate-co-N-isopropyl acrylamide) Microgels for Doxorubicin Delivery

“…Our previous experience in fabrication of microgels 22 with good colloidal stability based on a methacryloyl-derivatized poly(vinyl alcohol) network 23 by water-in-water microemulsions provided the background for incorporating NiPAAm in the * To whom correspondence should be addressed. E-mail: paradossi@ stc.uniroma2.it.…”

Synthesis and gelation properties of poly(2-alkyl-2-oxazoline) based thermo-gels

“…Several thermo-gelling materials have been reported including poly(esters) 6 , Pluronic® derivatives 4 , poly(amides) 7 and poly(acrylamides) [8][9][10] . In particular, poly(acrylamide) thermogels have acquired significant attention.…”