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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) A thermogram showing the glass transition temperatures of (a) PLGA polymer (32.7°C), PLGA loaded with (b) 20 mg (32.8°C), (c), 10 mg (15.2°C), and (d) 0 mg OP (5.8°C). (B) Cumulative release kinetics for PLGA blank, 10 mg and 20 mg OP loaded PLGA. All PLGA-OP samples exhibited a biphasic release profile.Abbreviations: OP, oseltamivir phosphate; PLGA, poly (lactic-co-glycolic acid).
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f2-dddt-9-4573: (A) A thermogram showing the glass transition temperatures of (a) PLGA polymer (32.7°C), PLGA loaded with (b) 20 mg (32.8°C), (c), 10 mg (15.2°C), and (d) 0 mg OP (5.8°C). (B) Cumulative release kinetics for PLGA blank, 10 mg and 20 mg OP loaded PLGA. All PLGA-OP samples exhibited a biphasic release profile.Abbreviations: OP, oseltamivir phosphate; PLGA, poly (lactic-co-glycolic acid).

Mentions: Differential scanning calorimetry shows the effect of OP loading on glass transition temperature (Tg) of the PLGA polymer making up the cylinders. Thermograms in Figure 2A reveal Tg of 5.8, 15.2, and 32.8°C with PLGA cylinders containing 0, 10, and 20 mg OP, respectively, and Tg of 32.7°C for native PLGA polymer. Tg values, while varied with drug loading, were all below body temperature, and therefore the glass transition.


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) A thermogram showing the glass transition temperatures of (a) PLGA polymer (32.7°C), PLGA loaded with (b) 20 mg (32.8°C), (c), 10 mg (15.2°C), and (d) 0 mg OP (5.8°C). (B) Cumulative release kinetics for PLGA blank, 10 mg and 20 mg OP loaded PLGA. All PLGA-OP samples exhibited a biphasic release profile.Abbreviations: OP, oseltamivir phosphate; PLGA, poly (lactic-co-glycolic acid).
© Copyright Policy
Related In: Results  -  Collection

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

f2-dddt-9-4573: (A) A thermogram showing the glass transition temperatures of (a) PLGA polymer (32.7°C), PLGA loaded with (b) 20 mg (32.8°C), (c), 10 mg (15.2°C), and (d) 0 mg OP (5.8°C). (B) Cumulative release kinetics for PLGA blank, 10 mg and 20 mg OP loaded PLGA. All PLGA-OP samples exhibited a biphasic release profile.Abbreviations: OP, oseltamivir phosphate; PLGA, poly (lactic-co-glycolic acid).
Mentions: Differential scanning calorimetry shows the effect of OP loading on glass transition temperature (Tg) of the PLGA polymer making up the cylinders. Thermograms in Figure 2A reveal Tg of 5.8, 15.2, and 32.8°C with PLGA cylinders containing 0, 10, and 20 mg OP, respectively, and Tg of 32.7°C for native PLGA polymer. Tg values, while varied with drug loading, were all below body temperature, and therefore the glass transition.

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