Poly(vinylcaprolactam)-Based Biodegradable Multiresponsive Microgels for Drug Delivery

Abstract

Poly(vinylcaprolactam) (PVCL)-based biodegradable microgels were prepared for the biomedical application as drug delivery system via precipitation polymerization, where N,N-bis(acryloyl) cystamine (BAC) served as cross-linker, methacrylic acid (MAA) and polyethylene glycol (PEG) methyl ether methacrylate acted as comonomers. The microgels with excellent stability had distinct temperature sensitivity as largely observed in the case of PVCL-based particles and their volume phase transition temperature (VPTT) shifted to higher temperature with increasing MAA content and ambient pH. In the presence of reducing agent glutathione (GSH) or dithiothreitol (DTT), the microgels could be degraded into individual linear polymer chains by the cleavage of the disulfide linkages coming from the cross-linker BAC. The microgels could effectively encapsulate Doxorubicin (DOX) inside and presented stimuli-triggered drug release in acidic or reducing environment. The results of the cytotoxicity assays further demonstrated that the blank microgels were nontoxic to normal cells while DOX-loaded microgels presented efficient antitumor activity to HeLa cells.

Poly(N-vinylcaprolactam), a comprehensive review on a thermoresponsive polymer becoming popular

“…It can be performed in the A variety of comonomers have been used in the preparation of micro-/nanogels of PNVCL (see Fig. 14): thermoresponsive as NIPAAm [157,173] and NIPMAAm [173] with reactive groups as glycidyl methacrylate [160,172,174], hydrophopic as acetoacetoxyethyl methacrylate (AAEM) [160][161][162][163][164][167][168][169], vinyl acetate [175], itaconic acid dimethyl ester (IADME) [176], and methyl methacrylate [48]; ionic comonomers such as the weak acids: acrylic acid [177], methacrylic acid [161,178], acrylamidoglycolic acid (AGA) [179], and sodium acrylate [180][181][182][183]; weak bases like vinylimidazole [176,184,185] and N,N'-dimethylaminoethylmethacrylate [186]; strong bases like 4-vinylpyridine (4VP) [187]; hydrophilic as N-vinylpyrrolidone [188,189], 3- [47,190], vinyl alcohol [191], vinyl-β-cyclodextrins (V-β-CD) and other cyclodextrins [192], and poly(ethylene glycol) methyl ether methacrylate (PEGMA) [155,178,[193][194]…”

“…The most widely used crosslinker for micro/nanogels is BIS [47,152,162,165,172,173,175,176,178,179,182,[184][185][186][187]189,192,193,195,198,200]; while other crosslinkers were also used: N,Nbis(acryloyl) cystamine (BAC) [178], poly(ethylene glycol) diacrylate (PEGDA)…”

“…Surfactants are very important in the preparation of micro-/nanogels because they stabilize precursor particles and minimize their growth by aggregation. Widely used surfactants in the preparation of PNVCL micro/nanogels are sodium dodecyl sulphate [47,177,178,179,187,193,200,201,203], sodium lauryl sulphate (SLS) [175], Ndodecylpyridinium bromide (DPB) [202], N-cetyl-N,N,N-trimethylammonium bromide (CTAB) [42,193], hexadecyltrimethylammonium bromide (HDTAB) [195], and sorbitan monoleate [165]. Table 3 summarizes the reagents and reaction conditions used in different syntheses carried out in dispersed media to produce cross-linked /NVCL-based micro/nanogels.…”

Intracellular delivery cellulose-based bionanogels with dual temperature/pH-response for cancer therapy

“…This stimuli-responsive platform leads to rapid release of encapsulated drugs. While most smart BNGs have been designed to exhibit single stimulus-response such as pH [36][37][38], temperature [39,40], enzymatic [41][42][43], or reductive reaction [44][45][46][47][48], dual or multiple stimuli-responsive BNGs exhibit more desirable drug release kinetics [49]. However, the exploration to synthesize dual responsive BNGs is in infancy, with few reports describing dual enzyme/light [49] and pH/reduction-responsive systems [50].…”

Incorporation of iron oxide nanoparticles into temperature-responsive poly (N-isopropylacrylamide-co-acrylic acid) P (NIPAAm-AA) polymer hydrogel

“…polymers are of much interest expected to offer controlled, self regulated immobilization and delivery, and recycling by magnet for repeated use [10]. Among stimuli responsive polymers, temperature responsive poly (N-isopropylacrylamide) poly (NIPAAm) is the most commonly studied and has played a successful role as a representative model to demonstrate how temperature can be modulated and explored in controlled applications [11,12]. Therefore, the particles that contain magnetic and temperature responsive poly (NIPAAm) have generated much interest for use in controlled switching manner [13].…”