CONTEXT: The sustained release implants can be directly implanted in tumor site by surgery and are promising for cancer treatment. OBJECTIVE: RGD-modified PEGylated polyamidoamine (PAMAM) dendrimer with doxorubicin (DOX) conjugated by acid-sensitive linkage (RGD-PPCD) was a potential conjugate for tumor-targeted therapy. In order to enhance tumor retention ability and long-term effect of drug, we developed the DOX and its conjugate implants using poly(dl-lactic-co-glycolic acid) (PLGA), poly(dl-lactic acid) (PLA) and polyethylene glycol (PEG) as carrier materials. METHODS: The implants were prepared by a simple solvent evaporation method. Different formulations with varying ratios of three polymers were designed, prepared and evaluated on the basis of viscosity, in vitro release and drying time. Furthermore, in vivo biodistribution and antitumor activity of the implants were studied in mice with subcutaneous C6 xenografts. RESULTS: The optimized formulation was obtained with the 3:1 ratio of PLGA/PLA (w/w) and 1% PEG (wt.%). The drug release behavior of DOX, PPCD and RGD-PPCD implants prepared by the optimized formulation was similar according to the assessment of similarity factor f2, and the release curves were fell into three phases, including a lag-period, then the second phase which was consistent with zero-order model followed by a plateau. Data of total DOX remained in implants indicated the release were faster in vivo than in vitro. Moreover, intratumoral drug amount of RGD-PPCD implants was the highest 45 days after implantation. Correspondingly, the RGD-PPCD implants exhibited the strongest antitumor activity compared with PPCD and free DOX implants. DISCUSSION AND CONCLUSION: This paper presents an exploratory research on macromolecule-drug conjugates, including RGD-PPCD and PPCD, which have the potential to be developed into long-term effect implants for tumor therapy with high efficiency and low systematic toxicity.
CONTEXT: The sustained release implants can be directly implanted in tumor site by surgery and are promising for cancer treatment. OBJECTIVE: RGD-modified PEGylated polyamidoamine (PAMAM) dendrimer with doxorubicin (DOX) conjugated by acid-sensitive linkage (RGD-PPCD) was a potential conjugate for tumor-targeted therapy. In order to enhance tumor retention ability and long-term effect of drug, we developed the DOX and its conjugate implants using poly(dl-lactic-co-glycolic acid) (PLGA), poly(dl-lactic acid) (PLA) and polyethylene glycol (PEG) as carrier materials. METHODS: The implants were prepared by a simple solvent evaporation method. Different formulations with varying ratios of three polymers were designed, prepared and evaluated on the basis of viscosity, in vitro release and drying time. Furthermore, in vivo biodistribution and antitumor activity of the implants were studied in mice with subcutaneous C6 xenografts. RESULTS: The optimized formulation was obtained with the 3:1 ratio of PLGA/PLA (w/w) and 1% PEG (wt.%). The drug release behavior of DOX, PPCD and RGD-PPCD implants prepared by the optimized formulation was similar according to the assessment of similarity factor f2, and the release curves were fell into three phases, including a lag-period, then the second phase which was consistent with zero-order model followed by a plateau. Data of total DOX remained in implants indicated the release were faster in vivo than in vitro. Moreover, intratumoral drug amount of RGD-PPCD implants was the highest 45 days after implantation. Correspondingly, the RGD-PPCD implants exhibited the strongest antitumor activity compared with PPCD and free DOX implants. DISCUSSION AND CONCLUSION: This paper presents an exploratory research on macromolecule-drug conjugates, including RGD-PPCD and PPCD, which have the potential to be developed into long-term effect implants for tumor therapy with high efficiency and low systematic toxicity.
Authors: Li Gao; Chuanqi Xie; Yuzhi Du; Xiaodong Wang; Erkang Xuan; Xiuxiu Liu; Yang Zhao; Jianjian Xu; Lan Luo Journal: Drug Deliv Date: 2017-11 Impact factor: 6.419
Authors: Monika Toporkiewicz; Justyna Meissner; Lucyna Matusewicz; Aleksander Czogalla; Aleksander F Sikorski Journal: Int J Nanomedicine Date: 2015-02-17
Authors: Li Gao; Lunyang Xia; Ruhui Zhang; Dandan Duan; Xiuxiu Liu; Jianjian Xu; Lan Luo Journal: Drug Des Devel Ther Date: 2017-10-20 Impact factor: 4.162
Authors: Li Gao; Shang Cai; Awei Cai; Yang Zhao; Tangbing Xu; Yan Ma; Yan Xu; Yuan Wang; Hao Wang; Yong Hu Journal: Drug Deliv Date: 2019-12 Impact factor: 6.419