Investigation on Injectable, Thermally and Physically Gelable Poly(Ethylene Glycol)/Poly(Octadecanedioic Anhydride) Amphiphilic Triblock Co-polymer Nanoparticles

Abstract

A family of injectable, biodegradable and thermosensitive co-polymer nanoparticle (NP) hydrogels based on mPEG-b-POA-b-mPEG, which was synthesized from mono-methoxy poly(ethylene glycol) (mPEG) and poly(octadecanedioic anhydride) (POA), was investigated in this paper. It was found that the aqueous dispersions of these NPs underwent a reversible gel-sol transition upon temperature change. By using paclitaxel and Bovine serum albumin (BSA) as model drugs, we noticed that the in vitro releases of both in situ gel-forming formulations were sustained and no initial burst releases were observed for 7 days. In vitro cytotoxicity tests via MTT assay indicate that mPEG-b-POA-b-mPEG NPs are non-toxic to normal mouse lung fibroblast cells (L929). The in vivo hydrogel formation and in vivo biocompatibility of co-polymer NP hydrogel were also investigated and the results further validate the biocompatible nature of co-polymer NP hydrogel. In conclusion, our mPEG-b-POA-b-mPEG NP hydrogel is able to control the release of incorporated drug for longer duration.

Sustained delivery of paclitaxel using thermogelling poly(PEG/PPG/PCL urethane)s for enhanced toxicity against cancer cells

“…These thermogelling copolymers have great applicative potential. Recently, many different injectable gel systems have been presented as carriers of chemotherapeutic drugs for cancer treatments 21–28. Presently, a thermogelling copolymer/drug formulation, OncoGel™ is being tested in clinical trials for the use of this product in a minimally invasive procedure for cancer treatment 29–41…”

“…Recently, many different injectable gel systems have been presented as carriers of chemotherapeutic drugs for cancer treatments. [21][22][23][24][25][26][27][28] Presently, a thermogelling copolymer/drug formulation, OncoGel TM is being tested in clinical trials for the use of this product in a minimally invasive procedure for cancer treatment. [29][30][31][32][33][34][35][36][37][38][39][40][41] The materials used in the synthesis of copolymers have widely been applied in the biomedical field.…”

Paclitaxel in tyrosine-derived nanospheres as a potential anti-cancer agent: In vivo evaluation of toxicity and efficacy in comparison with paclitaxel in Cremophor

“…Development of novel PTX delivery systems include, but is not limited to, nanoparticles (Cheng et al, 2011; Damascelli et al, 2003; Desai et al, 2006; Liang et al, 2011; Milane et al, 2011; Potineni et al, 2003; Reul et al, 2011; Shenoy et al, 2005), micelles (Liggins and Burt, 2002; Tsallas et al, 2010), liposomes (Heney et al, 2010; Kunstfeld et al, 2003; Rivera, 2003), dendrimers (Lim and Simanek, 2008; Minko et al, 2010; Ooya et al, 2004), superparamagnetic nanoparticles (Dilnawaz et al, 2010; Johnson et al, 2010; Zhao et al, 2010), polymer-based nanoshells (Zahr and Pishko, 2007), silica-based nanoparticles (Lu et al, 2007), and carbon nanotubes (Liu et al, 2008). Among these, nanoparticles based on biodegradable synthetic amphiphilic polymers have received the majority of attention due to ease of fabrication, stability (compared to liposomes), specificity, significant drug encapsulation/solubilization, and biocompatibility as a result of their material composition (Grodzinski et al, 2006).…”