Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapy

<p>Abstract</p> <p>Background</p> <p>Nanoparticle based delivery of anticancer drugs have been widely investigated. However, a very important process for Research & Development in any pharmaceutical industry is scaling nanoparticle formulation techniques so as to pr...

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Main Authors: Ranjan Amalendu P, Mukerjee Anindita, Helson Lawrence, Vishwanatha Jamboor K
Format: Article
Language:English
Published: BMC 2012-08-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:http://www.jnanobiotechnology.com/content/10/1/38
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spelling doaj-5fd21c79983744fdbb9dbf432cfacf322020-11-24T22:14:39ZengBMCJournal of Nanobiotechnology1477-31552012-08-011013810.1186/1477-3155-10-38Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapyRanjan Amalendu PMukerjee AninditaHelson LawrenceVishwanatha Jamboor K<p>Abstract</p> <p>Background</p> <p>Nanoparticle based delivery of anticancer drugs have been widely investigated. However, a very important process for Research & Development in any pharmaceutical industry is scaling nanoparticle formulation techniques so as to produce large batches for preclinical and clinical trials. This process is not only critical but also difficult as it involves various formulation parameters to be modulated all in the same process.</p> <p>Methods</p> <p>In our present study, we formulated curcumin loaded poly (lactic acid-co-glycolic acid) nanoparticles (PLGA-CURC). This improved the bioavailability of curcumin, a potent natural anticancer drug, making it suitable for cancer therapy. Post formulation, we optimized our process by Reponse Surface Methodology (RSM) using Central Composite Design (CCD) and scaled up the formulation process in four stages with final scale-up process yielding 5 g of curcumin loaded nanoparticles within the laboratory setup. The nanoparticles formed after scale-up process were characterized for particle size, drug loading and encapsulation efficiency, surface morphology, <it>in vitro</it> release kinetics and pharmacokinetics. Stability analysis and gamma sterilization were also carried out.</p> <p>Results</p> <p>Results revealed that that process scale-up is being mastered for elaboration to 5 g level. The mean nanoparticle size of the scaled up batch was found to be 158.5 ± 9.8 nm and the drug loading was determined to be 10.32 ± 1.4%. The <it>in vitro</it> release study illustrated a slow sustained release corresponding to 75% drug over a period of 10 days. The pharmacokinetic profile of PLGA-CURC in rats following i.v. administration showed two compartmental model with the area under the curve (AUC<sub>0-∞</sub>) being 6.139 mg/L h. Gamma sterilization showed no significant change in the particle size or drug loading of the nanoparticles. Stability analysis revealed long term physiochemical stability of the PLGA-CURC formulation.</p> <p>Conclusions</p> <p>A successful effort towards formulating, optimizing and scaling up PLGA-CURC by using Solid-Oil/Water emulsion technique was demonstrated. The process used CCD-RSM for optimization and further scaled up to produce 5 g of PLGA-CURC with almost similar physicochemical characteristics as that of the primary formulated batch.</p> http://www.jnanobiotechnology.com/content/10/1/38Scale upOptimizationPLGA nanoparticlesCancerResponse surface methodology (RSM)Curcumin C3 complexCentral composite design (CCD)
collection DOAJ
language English
format Article
sources DOAJ
author Ranjan Amalendu P
Mukerjee Anindita
Helson Lawrence
Vishwanatha Jamboor K
spellingShingle Ranjan Amalendu P
Mukerjee Anindita
Helson Lawrence
Vishwanatha Jamboor K
Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapy
Journal of Nanobiotechnology
Scale up
Optimization
PLGA nanoparticles
Cancer
Response surface methodology (RSM)
Curcumin C3 complex
Central composite design (CCD)
author_facet Ranjan Amalendu P
Mukerjee Anindita
Helson Lawrence
Vishwanatha Jamboor K
author_sort Ranjan Amalendu P
title Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapy
title_short Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapy
title_full Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapy
title_fullStr Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapy
title_full_unstemmed Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapy
title_sort scale up, optimization and stability analysis of curcumin c3 complex-loaded nanoparticles for cancer therapy
publisher BMC
series Journal of Nanobiotechnology
issn 1477-3155
publishDate 2012-08-01
description <p>Abstract</p> <p>Background</p> <p>Nanoparticle based delivery of anticancer drugs have been widely investigated. However, a very important process for Research & Development in any pharmaceutical industry is scaling nanoparticle formulation techniques so as to produce large batches for preclinical and clinical trials. This process is not only critical but also difficult as it involves various formulation parameters to be modulated all in the same process.</p> <p>Methods</p> <p>In our present study, we formulated curcumin loaded poly (lactic acid-co-glycolic acid) nanoparticles (PLGA-CURC). This improved the bioavailability of curcumin, a potent natural anticancer drug, making it suitable for cancer therapy. Post formulation, we optimized our process by Reponse Surface Methodology (RSM) using Central Composite Design (CCD) and scaled up the formulation process in four stages with final scale-up process yielding 5 g of curcumin loaded nanoparticles within the laboratory setup. The nanoparticles formed after scale-up process were characterized for particle size, drug loading and encapsulation efficiency, surface morphology, <it>in vitro</it> release kinetics and pharmacokinetics. Stability analysis and gamma sterilization were also carried out.</p> <p>Results</p> <p>Results revealed that that process scale-up is being mastered for elaboration to 5 g level. The mean nanoparticle size of the scaled up batch was found to be 158.5 ± 9.8 nm and the drug loading was determined to be 10.32 ± 1.4%. The <it>in vitro</it> release study illustrated a slow sustained release corresponding to 75% drug over a period of 10 days. The pharmacokinetic profile of PLGA-CURC in rats following i.v. administration showed two compartmental model with the area under the curve (AUC<sub>0-∞</sub>) being 6.139 mg/L h. Gamma sterilization showed no significant change in the particle size or drug loading of the nanoparticles. Stability analysis revealed long term physiochemical stability of the PLGA-CURC formulation.</p> <p>Conclusions</p> <p>A successful effort towards formulating, optimizing and scaling up PLGA-CURC by using Solid-Oil/Water emulsion technique was demonstrated. The process used CCD-RSM for optimization and further scaled up to produce 5 g of PLGA-CURC with almost similar physicochemical characteristics as that of the primary formulated batch.</p>
topic Scale up
Optimization
PLGA nanoparticles
Cancer
Response surface methodology (RSM)
Curcumin C3 complex
Central composite design (CCD)
url http://www.jnanobiotechnology.com/content/10/1/38
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AT mukerjeeanindita scaleupoptimizationandstabilityanalysisofcurcuminc3complexloadednanoparticlesforcancertherapy
AT helsonlawrence scaleupoptimizationandstabilityanalysisofcurcuminc3complexloadednanoparticlesforcancertherapy
AT vishwanathajamboork scaleupoptimizationandstabilityanalysisofcurcuminc3complexloadednanoparticlesforcancertherapy
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