Korean J Gynecol Oncol.
2007 Dec;18(4):289-298.
Development of a therapeutic method in the HPV-related cervical lesion using pH/temperature sensitive polymer spray formulation
- Affiliations
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- 1Department of Obstetrics and Gynecology, Catholic University Medical College, Seoul, Korea. jspark@catholic.ac.kr
- 2Division of Nano Sciences, Department of Chemistry, Ewha Womans University, Seoul, Korea.
- 3Laboratory of Infection and Immunology Graduate, School of Medicine, Korea University, Seoul, Korea.
- 4School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Seoul, Korea.
- 5Department of Pathology, Samsung Cheil Hospital, Kwandong University College of Medicine, Seoul, Korea.
Abstract
OBJECTIVE
The causal link between oncogenic HPV(Human Papilloma Viruses) and the development of CIN (rvical intraepithelial neoplasia) and cervical cancer are now well established. Several medical therapeutic candidates aimd at the treatment of precancerous lesions and invasive carcinoma of the cervix. The objective of this study was to develop the pH-sensitive chitosan/alginate gels (pH=3.8-4.5) and temperature sensitive multiblock copolymers of PEG/PLA (poly (L-lactic acid)/polyethylene glycol) gels (temperature=37 degrees C) for controlled delivery of the paclitaxel (PTX). We had also evaluated whether PTX entrapped in chitosan/alginate gels or multiblock copolymers of PEG/PLA 1 could inhibit tumor growth in vivo.
METHODS
PTX entrapped as microsphere in Chitosan/Alginate Microspheres were obtained using a spray-drying method. PTX-entrapped PEG/PLA gels were prepared by the solvent displacement method. We had prepared the multiblock copolymers of PEG/PLA which has the sol-gel-sol transition temperature at body temperature. The in-vivo efficacy of PTX in chitosan microphere or PTX in PEG/PLA mutiblock copolymer micelle were conducted in HeLa-tumor bearing Balb/c Nu/Nu athymic mice at an equivalent paclitaxel dose of 10 mg/kg with 48 hr interval. The inhibition of tumor growth was evaluated after 8 days of treatment.
RESULTS
On 8 days after the transcutaneous treatment of PTX-containing chitosan microphere or PTX in PEG/PLA mutiblock copolymer micelle. significant inhibition in tumor growth was observed in balb/c nu/nu nude mouse carrying xenograft tumors (HeLa cells; HPV-18 positive state). Among these formulations, PTX in PEG/PLA mutiblock copolymer have shown improved therapeutic efficacy as compared to PTX-ivgroup.
CONCLUSION
PTX-containing chitosan microphere or PTX in PEG/PLA mutiblock copolymer nanoparticles are a unique pH-sensitive and temperature sensitive drug delivery system. These formulations elicits enhanced efficacy as an effective and minimally invasive treatment in mice bearing human cervical cancer (HeLa Cells) xenograft.
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