Intratumoral Delivery of Paclitaxel in Solid Tumor from Biodegradable Hyaluronan Nanoparticle Formulations

Abstract

Abstract. In the current study, novel paclitaxel-loaded cross-linked hyaluronan nanoparticles were engineered for the local delivery of paclitaxel as a prototype drug for cancer therapy. The nanoparticles were prepared using a desolvation method with polymer cross-linking. In vitro cytotoxicity studies demonstrated that less than 75% of the MDA-MB-231 and ZR-75-1 breast cancer cells were viable after 2-day exposure to paclitaxel-loaded hyaluronan nanoparticles or free paclitaxel, regardless of the dose. These results suggest that hyaluronan nanoparticles maintain the pharmacological activity of paclitaxel and efficiently deliver it to the cells. Furthermore, in vivo administration of the drug-loaded nanoparticles via direct intratumoral injection to 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor in female rats was studied. The paclitaxel-loaded nanoparticles treated group showed effective inhibition of tumor growth in all treated rats. Interestingly, there was one case of complete remission of tumor nodule and two cases of persistent reduction of tumor size that was observed on subsequent days. In the case of free paclitaxel-treated group, the mean tumor volume increased almost linearly (R 2 =0.93) with time to a size that was 4.9-fold larger than the baseline volume at 57 days post-drug administration. Intratumoral administration of paclitaxel-loaded hyaluronan nanoparticles could be a promising treatment modality for solid mammary tumors.

Effect of intratumoral administration on biodistribution of 64Cu-labeled nanoshells

“…13 However, these concerns are not necessarily significant for some contemporary cancer agents. For example, there have been many reports of intratumoral injection of different nanocompositions, such as liposomes, 14,15 magnetic cationic liposomes, 16 hyaluronan nanoparticle formulations, 17 N-(2-hydroxypropyl)-methacrylamide copolymer, 13 cisplatin-loaded polycaprolactone polymers, 18 holmium-loaded poly-L-lactide polymers, 19 docetaxelloaded polycaprolactone polymers, 20 multiwalled carbon nanotubes, 21 gold-dendrimer composite nanodevices, 22 folateconjugated shell cross-linked nanoparticles, 23 and gum Arabic glycoprotein-functionalized gold nanoparticles. 24 However, intratumoral injection of other newly developed nanoparticles has been rarely reported, although it is theoretically a good route of administration.…”

Preparation and Characterization of Amphiphilic Calixarene Nanoparticles as Delivery Carriers for Paclitaxel

“…The tetracarboxylic acid of p-tert-butylcalix [4] In the development of water-soluble calixarenes, some hydrophilic-modified calixarenes were found to exhibit amphipathy and self-assemble into nano-aggregates in aqueous solutions, which were suitable for the delivery of hydrophobic antitumor drugs. An amphiphilic tetrahexyloxy-tetra-paminocalix[4] arene (A4C 6 ) was synthesized and used as a nanoparticle delivery platform for PTX.33) PTX-loaded A4C 6 nanoparticles had an average diameter of 79±21 nm and a drug loading efficiency of approximately 6.5%, and the release of PTX from A4C 6 nanoparticles could be sustained for at least 72 h. Amphoteric calix [8] arenes with a negatively charged sulfonated upper rim and a positively charged quaternary ammonium lower rim were synthesized and could …”

“…33) PTX-loaded A4C 6 nanoparticles had an average diameter of 79±21 nm and a drug loading efficiency of approximately 6.5%, and the release of PTX from A4C 6 nanoparticles could be sustained for at least 72 h. Amphoteric calix [8] arenes with a negatively charged sulfonated upper rim and a positively charged quaternary ammonium lower rim were synthesized and could…”

“…5) A liposomebased PTX formulation, Lipusu, has been applied for the treatment of ovarian cancer in China. 6) In addition to these approved drugs, a number of PTX nano-DDSs, such as polymeric nanoparticles (NPs), [7][8][9] inorganic NPs, 10) nano-emulsions, 11) carbon nanotubes, 12) and nanogels, 13) have been reported in preclinical studies. Although these novel PTX nano-DDSs exhibit varying levels of success, methods for improving the safety, stability and specificity of nano-DDS still warrant further research.…”

Future trends and emerging issues for nanodelivery systems in oral and oropharyngeal cancer

“…Following this, 60 patients who suffered from stage T3/4 oral cancer participated in Phase II of the trial, where the positive effects were reaffirmed, providing an encouraging new approach for preliminary chemotherapy in tongue SCC. [105][106][107] Another Phase I trial investigated the use of NP albumin-bound paclitaxel (Abraxane) in designing a regimen combining cetuximab-loaded NPs with radiation therapy. A total of 25 patients with stage III-IVB HNSCC took the proposed treatment, and the researchers determined an optimum dose of NPs that could be further investigated and administered to patients already undergoing cetuximab and radiation therapy.…”