Limits...
Therapeutic designed poly (lactic-co-glycolic acid) cylindrical oseltamivir phosphate-loaded implants impede tumor neovascularization, growth and metastasis in mouse model of human pancreatic carcinoma.

Hrynyk M, Ellis JP, Haxho F, Allison S, Steele JA, Abdulkhalek S, Neufeld RJ, Szewczuk MR - Drug Des Devel Ther (2015)

Bottom Line: Surgically implanted PLGA-OP containing 20 mg OP and blank PLGA cylinders at the tumor site of heterotopic xenografts of human pancreatic PANC1 tumors in RAGxCγ double mutant mice impeded tumor neovascularization, growth rate, and spread to the liver and lungs compared with the untreated cohort.Xenograft tumors from PLGA and PLGA-OP-treated cohorts expressed significant higher levels of human E-cadherin with concomitant reduced N-cadherin and host CD31(+) endothelial cells compared with the untreated cohort.These results clearly indicate that OP delivered from PLGA cylinders surgically implanted at the site of the solid tumor show promise as an effective treatment therapy for cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, Queen's University, Kingston, ON, Canada.

ABSTRACT
Poly (lactic-co-glycolic acid) (PLGA) copolymers have been extensively used in cancer research. PLGA can be chemically engineered for conjugation or encapsulation of drugs in a particle formulation. We reported that oseltamivir phosphate (OP) treatment of human pancreatic tumor-bearing mice disrupted the tumor vasculature with daily injections. Here, the controlled release of OP from a biodegradable PLGA cylinder (PLGA-OP) implanted at tumor site was investigated for its role in limiting tumor neovascularization, growth, and metastasis. PLGA-OP cylinders over 30 days in vitro indicated 20%-25% release profiles within 48 hours followed by a continuous metronomic low dose release of 30%-50% OP for an additional 16 days. All OP was released by day 30. Surgically implanted PLGA-OP containing 20 mg OP and blank PLGA cylinders at the tumor site of heterotopic xenografts of human pancreatic PANC1 tumors in RAGxCγ double mutant mice impeded tumor neovascularization, growth rate, and spread to the liver and lungs compared with the untreated cohort. Xenograft tumors from PLGA and PLGA-OP-treated cohorts expressed significant higher levels of human E-cadherin with concomitant reduced N-cadherin and host CD31(+) endothelial cells compared with the untreated cohort. These results clearly indicate that OP delivered from PLGA cylinders surgically implanted at the site of the solid tumor show promise as an effective treatment therapy for cancer.

No MeSH data available.


Related in: MedlinePlus

(A) PLGA-OP treatment of RAGxCγ double mutant mice bearing heterotopic xenografts of pancreatic PANC1 tumors. Cells at 0.5×106 in 0.2 mL were implanted subcutaneously in the right back flank of these mice. Twice a week following implantation of the PANC1 cancer cells, each mouse was monitored for tumor volume ((width squared/2) × length) at the site of implantation. Mice were surgically implanted with sterilized PLGA-empty (four mice) and PLGA-OP (four mice cylinders) containing 20 mg OP at day 35 post-implantation of cancer cells when the tumor volume reached approximately 50–120 mm3. (B) Graph of mean ± SEM of live necropsy tumor weight per mouse body weight. Statistical analysis using unpaired t-test was carried out using GraphPad Prism, and the results were compared with untreated control cohort.Abbreviations: OP, oseltamivir phosphate; PLGA, poly (lactic-co-glycolic acid); SEM, standard error of the mean; RAG, recombinase activating gene.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4539083&req=5

f3-dddt-9-4573: (A) PLGA-OP treatment of RAGxCγ double mutant mice bearing heterotopic xenografts of pancreatic PANC1 tumors. Cells at 0.5×106 in 0.2 mL were implanted subcutaneously in the right back flank of these mice. Twice a week following implantation of the PANC1 cancer cells, each mouse was monitored for tumor volume ((width squared/2) × length) at the site of implantation. Mice were surgically implanted with sterilized PLGA-empty (four mice) and PLGA-OP (four mice cylinders) containing 20 mg OP at day 35 post-implantation of cancer cells when the tumor volume reached approximately 50–120 mm3. (B) Graph of mean ± SEM of live necropsy tumor weight per mouse body weight. Statistical analysis using unpaired t-test was carried out using GraphPad Prism, and the results were compared with untreated control cohort.Abbreviations: OP, oseltamivir phosphate; PLGA, poly (lactic-co-glycolic acid); SEM, standard error of the mean; RAG, recombinase activating gene.

Mentions: Data presented in Figure 3A show that OP released from PLGA-OP 20 mg cylinders effectively inhibited tumor growth for approximately 30 days when implanted at day 35. Beyond this point, the tumor grew slightly, eventually reaching a volume similar to that of the blank PLGA cohorts by day 77. Tumor growth rate was substantial for the untreated control cohort. It is noteworthy that the 30-day period of tumor suppression in mice receiving PLGA-OP cylinders was consistent with the in vitro 30-day OP release period observed in Figure 2B.


Therapeutic designed poly (lactic-co-glycolic acid) cylindrical oseltamivir phosphate-loaded implants impede tumor neovascularization, growth and metastasis in mouse model of human pancreatic carcinoma.

Hrynyk M, Ellis JP, Haxho F, Allison S, Steele JA, Abdulkhalek S, Neufeld RJ, Szewczuk MR - Drug Des Devel Ther (2015)

(A) PLGA-OP treatment of RAGxCγ double mutant mice bearing heterotopic xenografts of pancreatic PANC1 tumors. Cells at 0.5×106 in 0.2 mL were implanted subcutaneously in the right back flank of these mice. Twice a week following implantation of the PANC1 cancer cells, each mouse was monitored for tumor volume ((width squared/2) × length) at the site of implantation. Mice were surgically implanted with sterilized PLGA-empty (four mice) and PLGA-OP (four mice cylinders) containing 20 mg OP at day 35 post-implantation of cancer cells when the tumor volume reached approximately 50–120 mm3. (B) Graph of mean ± SEM of live necropsy tumor weight per mouse body weight. Statistical analysis using unpaired t-test was carried out using GraphPad Prism, and the results were compared with untreated control cohort.Abbreviations: OP, oseltamivir phosphate; PLGA, poly (lactic-co-glycolic acid); SEM, standard error of the mean; RAG, recombinase activating gene.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4539083&req=5

f3-dddt-9-4573: (A) PLGA-OP treatment of RAGxCγ double mutant mice bearing heterotopic xenografts of pancreatic PANC1 tumors. Cells at 0.5×106 in 0.2 mL were implanted subcutaneously in the right back flank of these mice. Twice a week following implantation of the PANC1 cancer cells, each mouse was monitored for tumor volume ((width squared/2) × length) at the site of implantation. Mice were surgically implanted with sterilized PLGA-empty (four mice) and PLGA-OP (four mice cylinders) containing 20 mg OP at day 35 post-implantation of cancer cells when the tumor volume reached approximately 50–120 mm3. (B) Graph of mean ± SEM of live necropsy tumor weight per mouse body weight. Statistical analysis using unpaired t-test was carried out using GraphPad Prism, and the results were compared with untreated control cohort.Abbreviations: OP, oseltamivir phosphate; PLGA, poly (lactic-co-glycolic acid); SEM, standard error of the mean; RAG, recombinase activating gene.
Mentions: Data presented in Figure 3A show that OP released from PLGA-OP 20 mg cylinders effectively inhibited tumor growth for approximately 30 days when implanted at day 35. Beyond this point, the tumor grew slightly, eventually reaching a volume similar to that of the blank PLGA cohorts by day 77. Tumor growth rate was substantial for the untreated control cohort. It is noteworthy that the 30-day period of tumor suppression in mice receiving PLGA-OP cylinders was consistent with the in vitro 30-day OP release period observed in Figure 2B.

Bottom Line: Surgically implanted PLGA-OP containing 20 mg OP and blank PLGA cylinders at the tumor site of heterotopic xenografts of human pancreatic PANC1 tumors in RAGxCγ double mutant mice impeded tumor neovascularization, growth rate, and spread to the liver and lungs compared with the untreated cohort.Xenograft tumors from PLGA and PLGA-OP-treated cohorts expressed significant higher levels of human E-cadherin with concomitant reduced N-cadherin and host CD31(+) endothelial cells compared with the untreated cohort.These results clearly indicate that OP delivered from PLGA cylinders surgically implanted at the site of the solid tumor show promise as an effective treatment therapy for cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, Queen's University, Kingston, ON, Canada.

ABSTRACT
Poly (lactic-co-glycolic acid) (PLGA) copolymers have been extensively used in cancer research. PLGA can be chemically engineered for conjugation or encapsulation of drugs in a particle formulation. We reported that oseltamivir phosphate (OP) treatment of human pancreatic tumor-bearing mice disrupted the tumor vasculature with daily injections. Here, the controlled release of OP from a biodegradable PLGA cylinder (PLGA-OP) implanted at tumor site was investigated for its role in limiting tumor neovascularization, growth, and metastasis. PLGA-OP cylinders over 30 days in vitro indicated 20%-25% release profiles within 48 hours followed by a continuous metronomic low dose release of 30%-50% OP for an additional 16 days. All OP was released by day 30. Surgically implanted PLGA-OP containing 20 mg OP and blank PLGA cylinders at the tumor site of heterotopic xenografts of human pancreatic PANC1 tumors in RAGxCγ double mutant mice impeded tumor neovascularization, growth rate, and spread to the liver and lungs compared with the untreated cohort. Xenograft tumors from PLGA and PLGA-OP-treated cohorts expressed significant higher levels of human E-cadherin with concomitant reduced N-cadherin and host CD31(+) endothelial cells compared with the untreated cohort. These results clearly indicate that OP delivered from PLGA cylinders surgically implanted at the site of the solid tumor show promise as an effective treatment therapy for cancer.

No MeSH data available.


Related in: MedlinePlus