High paclitaxel-loaded and tumor cell-targeting hyaluronan-coated nanoemulsions.
The purpose of this study was to develop hyaluronan-coated nanoemulsions (HNEs) with high solubilizing capacity and tumor cell targeting capability for the poorly soluble paclitaxel. The HNEs were composed of dl-a-tocopheryl acetate, soybean oil, polysorbate 80, and ferric chloride and were coated with hyaluronic acid (HA) as a targeting moiety. The nanoemulsions (NEs) and HNEs with or without paclitaxel (PTX) were prepared using high-pressure homogenization with a microfluidizer and were lyophilized with d-mannitol. The particle diameter and zeta potential of the HNEs were 65±15nm and -39.5±0.33mV, respectively. The concentration of PTX loaded in the NEs was 6mg/mL, which was higher than that in any other nanocarrier. The HNEs were coated with HA on the outer surface of the sphere and the amount of HA was 0.82±0.10% (w/w). The lyophilized formulation was stable at 4°C for 12 months and the reconstituted HNE solution was stable for at least 96h, even though Taxol®can be maintained for only 72h. In the cell affinity studies with SK-OV-3 (cluster of differentiation 44 [CD44]+) and OVCAR-3 (CD44-) cells, the HNEs displayed a 10-fold higher targeting capability than the NEs did. Therefore, the HNEs displayed high drug loading capability, excellent stability, and targeting of tumor cells overexpressing CD44, which suggested they were a potentially effective nanocarrier for carrying poorly soluble paclitaxel and targeting tumors.
College of Pharmacy, Ajou University, Suwon City 443-749, Republic of Korea.
Joo-Eun
JE
Kim
College of Pharmacy, Ajou University, Suwon City 443-749, Republic of Korea. Electronic address: parkyj64@gmail.com.
Young-Joon
YJ
Park
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002712:Chlorides / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004655:Emulsions / Q000737:chemistry*; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage*; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D012995:Solubility; D013024:Soybean Oil / Q000737:chemistry; D013696:Temperature; D024502:alpha-Tocopherol / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D002712:Chlorides; D004337:Drug Carriers; D004655:Emulsions; D005290:Ferric Compounds; D018960:Hyaluronan Receptors; D011136:Polysorbates; D013024:Soybean Oil; D006820:Hyaluronic Acid; D024502:alpha-Tocopherol; D017239:Paclitaxel; C024555:ferric chloride
Hyaluronan; Nanoemulsion; Paclitaxel; Solubilization; Stability; Targeting