13 research outputs found
Biodistribution of biodegradable polymeric nano-carriers loaded with busulphan and designed for multimodal imaging
Synthesis of Polymeric Nanocomposites for Drug Delivery and Bioimaging
Nanomaterials have gained great attention for biomedical applications due to their extraordinary physico-chemical and biological properties. The current dissertation presents the design and development of multifunctional nanoparticles for molecular imaging and controlled drug delivery applications which include biodegradable polymeric nanoparticles, superparamagnetic iron oxide nanoparticles (SPION)/polymeric nanocomposite for magnetic resonance imaging (MRI) and drug delivery, manganese-doped zinc sulfide (Mn:ZnS) quantum dots (QDs)/ SPION/ polymeric nanocomposites for fluorescence imaging, MRI and drug delivery.Bioimaging is an important function of multifunctional nanoparticles in this thesis. Imaging probes were made of SPION and Mn:ZnS QDs for in vitro and in vivo imaging. The SPION have been prepared through a high temperature decomposition method to be used as MRI contrast agent. SPION and Mn:ZnS were encapsulated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles during the particles formation. The hydrophobic model drug, busulphan, was loaded in the PLGA vesicles in the composite particles. T2*-weighted MRI of SPION-Mn:ZnS-PLGA phantoms exhibited enhanced negative contrast with r2* relaxivity of 523 mM-1 s-1. SPION-Mn:ZnS-PLGA-NPs have been successfully applied to enhance the contrast of liver in rat model.The biodegradable and biocompatible poly (ethylene glycol)-co-poly (caprolactone) (PEG-PCL) was used as matrix materials for polymeric nanoparticles -based drug delivery system. The PEG-PCL nanoparticles have been constructed to encapsulate SPION and therapeutic agent. The encapsulation efficiency of busulphan was found to be ~ 83 %. PEG-PCL nanoparticles showed a sustained release of the loaded busulphan over a period of 10 h. The SPION-PEG-PCL phantoms showed contrast enhancement in T2*-weighted MRI. Fluorescein-labeled PEG-PCL nanoparticles have been observed in the cytoplasm of the murine macrophage cells (J774A) by fluorescence microscopy. Around 100 % cell viability were noticed for PEG-PCL nanoparticles when incubated with HL60 cell line. The in vivo biodistribution of fluorescent tagged PEG-PCL nanoparticles demonstrated accumulation of PEG-PCL nanoparticles in different tissues including lungs, spleen, liver and kidneys after intravenous administration.QC 20160516</p
Biodistribution of Busulphan Loaded Biodegradable Nano-carrier Designed for Multimodal Imaging
Multifunctional nanocarriers for pathological site imaging and regulated drug delivery are increasingly promising for disease diagnosis and treatment. We developed a multifunctional theranostic nanocarrier system for anticancer drug delivery and molecular imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) as an MRI contrast agent and busulphan as an antineoplastic agent were encapsulated into poly (ethylene glycol)-co-poly (caprolactone) (PEG-PCL) nanoparticles (NPs) via the emulsion-evaporation method. Busulphan entrapment efficiency was 83% and the drug release showed a sustained pattern over 10 hours. SPION loaded-PEG-PCL NPs showed contrast enhancement in T2*-weighted MRI with high r2* relaxivity. In vitro time-dependent cellular PEG-PCL NP uptake was observed in macrophage cells (J774A). PEG-PCL NPs were further functionalized with VivoTag 680XL Fluorochrome for in vivo fluorescence imaging for study of their biodistribution in Balb/c mice over 48 h. The results of real-time imaging were then confirmed by ex vivo organ imaging and histological examination. Generally, PEG-PCL NPs were highly distributed in the lungs until 4 h post intravenous administration, then redistributed and accumulated in liver and spleen until 48 h. No pathological impairment was found in the studied tissues. Thus, PEG-PCL NPs as biodegradable and biocompatible nanocarriers are an efficient multimodal imaging agent, offer high drug loading capacity, and provide the possibility of disease treatment.QC 20160518</p
Biodistribution of Busulphan Loaded Biodegradable Nano-carrier Designed for Multimodal Imaging
Multifunctional nanocarriers for pathological site imaging and regulated drug delivery are increasingly promising for disease diagnosis and treatment. We developed a multifunctional theranostic nanocarrier system for anticancer drug delivery and molecular imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) as an MRI contrast agent and busulphan as an antineoplastic agent were encapsulated into poly (ethylene glycol)-co-poly (caprolactone) (PEG-PCL) nanoparticles (NPs) via the emulsion-evaporation method. Busulphan entrapment efficiency was 83% and the drug release showed a sustained pattern over 10 hours. SPION loaded-PEG-PCL NPs showed contrast enhancement in T2*-weighted MRI with high r2* relaxivity. In vitro time-dependent cellular PEG-PCL NP uptake was observed in macrophage cells (J774A). PEG-PCL NPs were further functionalized with VivoTag 680XL Fluorochrome for in vivo fluorescence imaging for study of their biodistribution in Balb/c mice over 48 h. The results of real-time imaging were then confirmed by ex vivo organ imaging and histological examination. Generally, PEG-PCL NPs were highly distributed in the lungs until 4 h post intravenous administration, then redistributed and accumulated in liver and spleen until 48 h. No pathological impairment was found in the studied tissues. Thus, PEG-PCL NPs as biodegradable and biocompatible nanocarriers are an efficient multimodal imaging agent, offer high drug loading capacity, and provide the possibility of disease treatment.QC 20160518</p
Biodistribution of Busulphan Loaded Biodegradable Nano-carrier Designed for Multimodal Imaging
Multifunctional nanocarriers for pathological site imaging and regulated drug delivery are increasingly promising for disease diagnosis and treatment. We developed a multifunctional theranostic nanocarrier system for anticancer drug delivery and molecular imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) as an MRI contrast agent and busulphan as an antineoplastic agent were encapsulated into poly (ethylene glycol)-co-poly (caprolactone) (PEG-PCL) nanoparticles (NPs) via the emulsion-evaporation method. Busulphan entrapment efficiency was 83% and the drug release showed a sustained pattern over 10 hours. SPION loaded-PEG-PCL NPs showed contrast enhancement in T2*-weighted MRI with high r2* relaxivity. In vitro time-dependent cellular PEG-PCL NP uptake was observed in macrophage cells (J774A). PEG-PCL NPs were further functionalized with VivoTag 680XL Fluorochrome for in vivo fluorescence imaging for study of their biodistribution in Balb/c mice over 48 h. The results of real-time imaging were then confirmed by ex vivo organ imaging and histological examination. Generally, PEG-PCL NPs were highly distributed in the lungs until 4 h post intravenous administration, then redistributed and accumulated in liver and spleen until 48 h. No pathological impairment was found in the studied tissues. Thus, PEG-PCL NPs as biodegradable and biocompatible nanocarriers are an efficient multimodal imaging agent, offer high drug loading capacity, and provide the possibility of disease treatment.QC 20160518</p
Protective Effect of DPPD on Mercury Chloride-Induced Hepatorenal Toxicity in Rats
Mercury is a global environmental pollutant, accumulating mainly in the kidney and liver inducing hepatorenal toxicity, oxidative stress, and tissue damage. Oxidative stress is caused by an imbalance between free radicals’ production and cellular antioxidant defense systems. In the present study, we investigated the effect of N N′-diphenyl-1, 4-phenylenediamine (DPPD) antioxidant activity against mercury chloride- (HgCl2-) induced renal and hepatic toxicity. Thirty adult female Sprague Dawley rats were divided into three equal groups: the first group was injected with saline only and served as a control, the second group was injected with HgCl2, and the third group received DPPD + HgCl2 rats injected with HgCl2 without treatment showing a significant increase in alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, and uric acids compared to control. Moreover, the second group showed a significant reduction in the activity of the antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH)) in addition to a marked increase in the malondialdehyde (MDA) content, histopathological alterations, collagen deposition, CD8%, CD4%, and TGF-β% in kidney and liver tissues compared with the control group. Treatment with DPPD showed significant recovery (p≤0.001) in all previous parameters and histopathological examination. In conclusion, we suggested that DPPD may have a promising antioxidant capacity, gives it the applicability to be used as a prophylactic agent against mercury-induced hepatorenal cytotoxicity in the future
Functional nano-carriers for drug delivery by surface engineering of polymeric nanoparticles post-PISA
Engineered polymeric nanoparticles (NPs) have been comprehensively explored as potential platforms for diagnosis and targeted therapy for several diseases including cancer. Herein, we designed functional poly(acrylic acid)-b-poly(butyl acrylate) (PAA-b-PBA) NPs using reversible addition-fragmentation chain-transfer (RAFT)-mediated emulsion polymerization via polymerization-induced self-assembly (PISA). The hydrophilic PAA-macroRAFT, forming a stabilizing shell (i.e. corona), was chain-extended using the hydrophobic monomer n-butyl acrylate (n-BA), resulting in stable, monodisperse and reproducible PAA-b-PBA NPs, typically having a diameter of 130 nm. Two approaches of surface engineering of the PAA-b-PBA NPs post-PISA were explored; a two-step and a one-step approach. In the two-step approach, the hydrophilic NP-shell corona was modified with allyl-groups under mild conditions using allylamine in water which resulted in stable allyl-functional NPs (allyl-NPs) suitable for further bio-conjugation. Their versatility was investigated by the subsequent conjugation of a thiol-functional fluorescent dye (BODIPY-SH) to the allyl-groups using click chemistry, in order to mimic the attachment of a thiol-functional target ligand. The average size and size distribution of the corresponding NPs did not change after BODIPY-conjugation. Neither the NPs nor allyl-NPs showed significant cytotoxicity towards RAW264.7 or MCF-7 cell lines, which indicates their desirable safety profile. A one-step approach to concurrently conjugate allyl-groups and a fluorescent dye (FITC) to the preformed PAA-b-PBA NPs was investigated. The cellular uptake of the FITC-NPs using J774A cells in vitro was found to be time- and concentration-dependent. The anti-cancer drug, doxorubicin, was efficiently (90%) encapsulated into the PAA-b-PBA NPs during NP formation. After a small burst release during the first two hours, a controlled release pattern over 7 days was observed. The present investigation demonstrates a potential method to functionalize polymeric NPs post-PISA to produce targeted drug delivery carriers.QC 20200214</p
Functional nano-carriers for drug delivery by surface engineering of polymeric nanoparticles post-PISA
Engineered polymeric nanoparticles (NPs) have been comprehensively explored as potential platforms for diagnosis and targeted therapy for several diseases including cancer. Herein, we designed functional poly(acrylic acid)-b-poly(butyl acrylate) (PAA-b-PBA) NPs using reversible addition-fragmentation chain-transfer (RAFT)-mediated emulsion polymerization via polymerization-induced self-assembly (PISA). The hydrophilic PAA-macroRAFT, forming a stabilizing shell (i.e. corona), was chain-extended using the hydrophobic monomer n-butyl acrylate (n-BA), resulting in stable, monodisperse and reproducible PAA-b-PBA NPs, typically having a diameter of 130 nm. Two approaches of surface engineering of the PAA-b-PBA NPs post-PISA were explored; a two-step and a one-step approach. In the two-step approach, the hydrophilic NP-shell corona was modified with allyl-groups under mild conditions using allylamine in water which resulted in stable allyl-functional NPs (allyl-NPs) suitable for further bio-conjugation. Their versatility was investigated by the subsequent conjugation of a thiol-functional fluorescent dye (BODIPY-SH) to the allyl-groups using click chemistry, in order to mimic the attachment of a thiol-functional target ligand. The average size and size distribution of the corresponding NPs did not change after BODIPY-conjugation. Neither the NPs nor allyl-NPs showed significant cytotoxicity towards RAW264.7 or MCF-7 cell lines, which indicates their desirable safety profile. A one-step approach to concurrently conjugate allyl-groups and a fluorescent dye (FITC) to the preformed PAA-b-PBA NPs was investigated. The cellular uptake of the FITC-NPs using J774A cells in vitro was found to be time- and concentration-dependent. The anti-cancer drug, doxorubicin, was efficiently (90%) encapsulated into the PAA-b-PBA NPs during NP formation. After a small burst release during the first two hours, a controlled release pattern over 7 days was observed. The present investigation demonstrates a potential method to functionalize polymeric NPs post-PISA to produce targeted drug delivery carriers.QC 20200214</p
Functional nano-carriers for drug delivery by surface engineering of polymeric nanoparticles post-PISA
Engineered polymeric nanoparticles (NPs) have been comprehensively explored as potential platforms for diagnosis and targeted therapy for several diseases including cancer. Herein, we designed functional poly(acrylic acid)-b-poly(butyl acrylate) (PAA-b-PBA) NPs using reversible addition-fragmentation chain-transfer (RAFT)-mediated emulsion polymerization via polymerization-induced self-assembly (PISA). The hydrophilic PAA-macroRAFT, forming a stabilizing shell (i.e. corona), was chain-extended using the hydrophobic monomer n-butyl acrylate (n-BA), resulting in stable, monodisperse and reproducible PAA-b-PBA NPs, typically having a diameter of 130 nm. Two approaches of surface engineering of the PAA-b-PBA NPs post-PISA were explored; a two-step and a one-step approach. In the two-step approach, the hydrophilic NP-shell corona was modified with allyl-groups under mild conditions using allylamine in water which resulted in stable allyl-functional NPs (allyl-NPs) suitable for further bio-conjugation. Their versatility was investigated by the subsequent conjugation of a thiol-functional fluorescent dye (BODIPY-SH) to the allyl-groups using click chemistry, in order to mimic the attachment of a thiol-functional target ligand. The average size and size distribution of the corresponding NPs did not change after BODIPY-conjugation. Neither the NPs nor allyl-NPs showed significant cytotoxicity towards RAW264.7 or MCF-7 cell lines, which indicates their desirable safety profile. A one-step approach to concurrently conjugate allyl-groups and a fluorescent dye (FITC) to the preformed PAA-b-PBA NPs was investigated. The cellular uptake of the FITC-NPs using J774A cells in vitro was found to be time- and concentration-dependent. The anti-cancer drug, doxorubicin, was efficiently (90%) encapsulated into the PAA-b-PBA NPs during NP formation. After a small burst release during the first two hours, a controlled release pattern over 7 days was observed. The present investigation demonstrates a potential method to functionalize polymeric NPs post-PISA to produce targeted drug delivery carriers.QC 20200214</p