Quaternized chitosan-coated nanofibrous implants loaded with gossypol prepared by electrospinning and their efficacy against Graffi myeloid tumor.
Nanofibrous poly(L-lactide-co-D,L-lactide) (coPLA) or coPLA/poly(ethylene glycol) implants loaded with plant polyphenolic compound gossypol (GOS) with anti-tumor activity were fabricated by electrospinning. Implants containing quaternized chitosan (QCh) were prepared by coating of the obtained fibrous materials with a thin film of cross-linked QCh. The morphology of the implants and chemical composition of the implant surface were studied by means of scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). In vitro cytotoxicity assay showed that GOS-loaded nanofibrous implants, both non-coated and QCh-coated displayed about two-fold higher inhibitory activity against Graffi tumor cells than that of free GOS at the 72nd h of incubation. As evidenced by the performed fluorescence microscopy analyses and SEM observations, the anti-tumor activity of the fibrous implants was mainly due to induction of apoptosis. The experiments in which the implants containing both QCh and GOS were placed locally into the tumor site after the tumor extirpation showed an increase in the survival rate and a lower rate of recurrence in the operative field and of metastases in regional lymph nodes. In this case, 40% of hamsters were alive on the 45th day of implantation and they did not show any clinical sign of recurrence in the operative field and metastases in the regional lymph nodes.
a Laboratory of Bioactive Polymers , Institute of Polymers, Bulgarian Academy of Sciences , Acad. G. Bonchev Street, bl. 103A, BG-1113 Sofia , Bulgaria.
Milena
M
Ignatova
Kalin
K
Kalinov
Nevena
N
Manolova
Reneta
R
Toshkova
Iliya
I
Rashkov
Marin
M
Alexandrov
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D006224:Cricetinae; D004337:Drug Carriers / Q000737:chemistry*; D004343:Drug Implants; D006072:Gossypol / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D009052:Leukemia Virus, Murine / Q000502:physiology; D057139:Nanofibers / Q000737:chemistry*; D036103:Nanotechnology; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
D000970:Antineoplastic Agents; D004337:Drug Carriers; D004343:Drug Implants; D011091:Polyesters; D011092:Polyethylene Glycols; C033616:poly(lactide); D048271:Chitosan; D006072:Gossypol