title: Intratumoral delivery of Paclitaxel in solid tumor from biodegradable hyaluronan nanoparticle formulations.
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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 927 Rose Street, Lexington, Kentucky 40536-0082, USA. amalg0@email.uky.edu
authors.forename: Abeer M
authors.initials: AM
authors.lastname: Al-Ghananeem
authors.forename: Ahmad H
authors.initials: AH
authors.lastname: Malkawi
authors.forename: Yahya M
authors.initials: YM
authors.lastname: Muammer
authors.forename: Justin M
authors.initials: JM
authors.lastname: Balko
authors.forename: Esther P
authors.initials: EP
authors.lastname: Black
authors.forename: Walid
authors.initials: W
authors.lastname: Mourad
authors.forename: Edward
authors.initials: E
authors.lastname: Romond
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D005260:Female; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D053758:Nanoparticles / Q000008:administration & dosage*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015127:9,10-Dimethyl-1,2-benzanthracene; D006820:Hyaluronic Acid; D017239:Paclitaxel