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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Development and optimisation of Polyelectrolyte Complex Nanoparticles Loaded with Sorafenib by Central Composite
Sangita A Kale1, Savita S Deokar2, Karimunnisa S Shaikh3
1Department of Pharmaceutics, Progressive Education Society's Modern College of Pharmacy, Savitribai Phule Pune University, Yamunanagar, Nigdi, Pune, Maharashtra, 411044, India.
Introduction:
Sorafenib (SOR) is a low-dose multikinase inhibitor that suppresses angiogenesis by blocking vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors. The aim of the present study was to develop Sorafenib-loaded chitosan (CS) and hyaluronic acid (HA) polyelectrolyte complex nanoparticles (SCH-NP) for triple negative breast cancer (TNBC).
Methods:
For TNBC therapy, SCH-NP were formulated and optimized using Central Composite Design (CCD). The prepared SCH-NP were characterized by particle size, zeta potential, Polydispersity index, Fourier Transform Infrared Spectroscopy (FTIR), entrapment efficiency, invitro drug release study, in-vitro and in vivo studies.
Results:
SCH-NP were formulated and optimized using CCD. The developed SCH-NP showed particle size of 125 nm, zeta potential of -13.7 mV, PDI value 0.21 and entrapment efficiency of 82.07%. FTIR study confirmed no interaction between drug and polysaccharide. The cumulative release percentage of SOR from SCH-NP was 81.73%. SOR's IC50 value was much larger than, SCH-NP's in both MDA-MB 231 & 4T1 cell lines. After treatment for 18 days, the tumor volumes in mice increased to 447.4 mm3 (Phosphate buffer solution), 263.6 mm3 (pure SOR), treatment with SCH-NP results in a noteworthy decrease in the tumor volumes in mice by 66.1% (151.3 mm3).
Conclusions:
The present study suggests that SCH-NP might be effective for the tumor-targeted delivery of Sorafenib and it might be a suitable nanocarrier for enhancing SOR cytotoxicity in vitro and may be useful for the tumor-targeted delivery of SOR.
Insights
New chitosan and hyaluronic acid nanoparticles effectively deliver Sorafenib for triple-negative breast cancer therapy. These Sorafenib-loaded nanoparticles significantly reduced tumor volume in mice, showing enhanced efficacy compared to the drug alone.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Sorafenib is a multikinase inhibitor targeting VEGF and PDGF receptors, crucial in angiogenesis.
- Triple-negative breast cancer (TNBC) presents a significant therapeutic challenge.
- Developing targeted drug delivery systems is vital for improving TNBC treatment outcomes.
Purpose of the Study:
- To develop and optimize Sorafenib-loaded chitosan and hyaluronic acid polyelectrolyte complex nanoparticles (SCH-NP).
- To evaluate the efficacy of SCH-NP for targeted delivery in TNBC therapy.
Main Methods:
- Formulation and optimization of SCH-NP using Central Composite Design (CCD).
- Characterization of SCH-NP including particle size, zeta potential, PDI, FTIR, and entrapment efficiency.
- In vitro drug release studies and cytotoxicity assays (IC50) against TNBC cell lines.
- In vivo studies to assess tumor volume reduction in a mouse model.
Main Results:
- Optimized SCH-NP exhibited a particle size of 125 nm, zeta potential of -13.7 mV, PDI of 0.21, and 82.07% entrapment efficiency.
- Fourier Transform Infrared Spectroscopy confirmed no drug-polysaccharide interaction.
- In vitro studies showed significantly lower IC50 values for SCH-NP compared to Sorafenib alone in MDA-MB 231 and 4T1 cell lines.
- In vivo, SCH-NP treatment resulted in a 66.1% reduction in tumor volume compared to controls and pure Sorafenib over 18 days.
Conclusions:
- Sorafenib-loaded chitosan-hyaluronic acid nanoparticles (SCH-NP) demonstrate potential as an effective nanocarrier for TNBC.
- SCH-NP enhance Sorafenib's cytotoxicity in vitro and show promising tumor-targeted delivery capabilities in vivo.
- This nanocarrier system may offer a viable strategy for improving Sorafenib efficacy in TNBC treatment.
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