A novel low molecular weight nanocomposite hydrogel formulation for intra-tumoural delivery of anti-cancer drugs

Abstract

Herein, an injectable formulation composed of a low molecular weight gelator (LMWG) based hydrogel and drug-loaded polymeric nanocapsules (NCs) is described. The NCs, made of hyaluronic acid and polyglutamic acid and loaded with C14-Gemcitabine (GEM C14), showed a size of 40 and 80 nm and a encapsulation efficiency > 90%. These NCs exhibited a capacity to control the release of the encapsulated drug for more than 1 month. GEM C14-loaded NCs showed activity against various cancer cell lines in vitro; cell growth inhibition by 50% (GI50) values of 15 ± 6, 10 ± 9, 13 ± 3 and 410 ± 463 nM were obtained in HCT 116, MIA PaCa-2, Panc-1 and Panc-1 GEM resistant cell lines respectively. Nanocomposite hydrogels were prepared using the LMWG -N4-octanoyl-2ʹ-deoxycytidine and loaded for the first time with polymeric NCs. 2% and 4% w/v nanocapsule concentrations as compared to 8% w/v NC concentrations with 2 % and 3% w/v gelator concentrations gave mechanically stronger gels as determined by oscillatory rheology. Most importantly, the nanocomposite formulation reformed instantly into a gel after injection through a needle. Based on these properties, the nanocomposite gel formulation has potential for the intratumoural delivery of anticancer drugs. 1 Abbreviations: low molecular weight gelator (LMWG); nanocapsules (NCs); N4-myristoyl gemcitabine (GEM C14); low molecular weight (LMW); hexadecyltrimethylammonium bromide (CTAB); Sodium hyaluronate (HA); poly-L-glutamic acid (PGA); GEM hydrochloride (GEM-HCl); 9-Diethylamino-5Hbenzo[a]phenoxazine-5-one -Nile Red (NR); Linear visco-elastic (LVE) region; GEM resistant cell line

Encapsulation and Characterization of Nanoemulsions Based on an Anti-oxidative Polymeric Amphiphile for Topical Apigenin Delivery

“…As addition of pure TPGS with NEs in a fixed 6% of HA, increasing SOR from 30% to 60% will slightly decrease the crossover modulus point and increasing the G' value, which may be related to a decrease in the surface tension. This similar phenomenon was reported elsewhere, in which an increase in dispersant concentration would lead to an increase on G' value of the gel formulations [49].…”

Nanocomposite sponges for enhancing intestinal residence time following oral administration

“…After 24 h blank NE showed toxicity at concentration higher than 156 µgꞏmL 1 , being the IC50 value of 336 µgꞏmL 1 . The value of IC50 of the blank NE was similar to that previously reported for lipid nanocapsules [59], polymeric nanocapsules [61,62] and solid lipid nanoparticles [63] when evaluated on the same colon cancer cell line (HCT-116).…”

Injectable Nanocomposite Hydrogels for Cancer Therapy

“…Polymeric NPs (e.g., poly‐ l ‐lactide NPs, [ 125 ] nanomicelle, [ 126 ] polymeric nanocapsules (NCs), [ 127 ] halloysite‐nanotubes, [ 128 ] and alginate NPs [ 129 ] ), play an important role in the preparation of NHs for fighting diseases. They have excellent characteristics, can be used as good preparation materials in the field of biomedicine, and have received widespread attention as new biological materials.…”