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.
Animals ; Body Temperature ; Cervix Uteri ; Chitosan ; Drug Delivery Systems ; Female ; Gels ; Heterografts ; Human papillomavirus 18 ; Humans ; Mice ; Mice, Nude ; Microspheres ; Nanoparticles ; Paclitaxel ; Papilloma ; Polymers* ; Transition Temperature ; Uterine Cervical Neoplasms

BACKGROUND: There have been bone mass studies for the treatment of osteoporosis, nonetheless, little attention has been paid to the management of osteopenia. This study was to evaluate the effects of estrogen, alendronate and their combination on bone mineral density and bone metabolism in the postmenopausal women with osteopenia. METHODS: A total of 150 healthy regional patients with osteopenia from Busan were enrolled in prospective randomized clinical trial and randomly assigned to receive conjugated equine estrogen (group I), alendronate (group II), or combination of the two (group III). Assessments included BMD of L2-4 spines and femur neck by DEXA and markers of bone turnover including serum osteocalcin, total alkaline phosphatase and urine deoxydyridinoline (Dpd). BMD and markers of bone turnover were re-evaluated at 6 and 12 months after the treatment. RESULTS: BMD of the lumbar spines increased significantly at 12 months after treatment in the three groups (P<0.05). BMD of the femur neck increased at 12 months after treatment in the three groups, but significantly in group III (P<0.05). Serum osteocalcin decreased at 12 months after treatment in the three groups, but only significantly in group III. Urine Dpd decreased at 12 months after treatment in three groups, but significantly in group, II and III (P<0.05). Serum total alkaline phosphatase decreased at 12 months after treatment in only group III (P<0.05). There was more favorable benefit for group III in BMD of the lumbar spines and serum osteocalcin and urine Dpd at 12 months after treatment compared to group, II and III (P<0.05). CONCLUSION: These results indicated a favorable benefit of conjugated equine estrogen, alendronate, or combination of the two in BMD and important markers of bone turnover. The combined treatment with conjugated equine estrogen and alendronate was more effective in postmenopausal women with osteopenia. Long-term studies are required to confirm these results.
Alendronate ; Alkaline Phosphatase ; Bone Density* ; Bone Diseases, Metabolic* ; Busan ; Estrogens ; Female ; Femur Neck ; Humans ; Metabolism* ; Osteocalcin ; Osteoporosis ; Prospective Studies ; Spine