CD44-Targeted, Indocyanine green-Paclitaxel-Loaded Human Serum Albumin Nanoparticles for Potential Image-Guided Drug Delivery

Author(s):  
Karthik Thangavel ◽  
Asha Lakshmikuttyamma ◽  
Chellappagounder Thangavel ◽  
Sunday A. Shoyele
PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0254305
Author(s):  
Nikita Lomis ◽  
Susan Westfall ◽  
Dominique Shum-Tim ◽  
Satya Prakash

Congestive heart failure, a prominent cardiovascular disease results primarily from myocardial infarction or ischemia. Milrinone (MRN), a widely used clinical drug for heart failure, improves myocardial contractility and cardiac function through its inotropic and vasodilatory effects. However, lacking target specificity, it exhibits low bioavailability and lower body retention time. Therefore, in this study, angiotensin II (AT1) peptide conjugated human serum albumin nanoparticles (AT1-HSA-MRN-NPs) have been synthesized for targeted delivery of MRN to the myocardium, overexpressing AT1 receptors under heart failure. The NPs were surface functionalized through a covalent conjugation reaction between HSA and AT1. Nanoparticle size was 215.2±4.7 nm and zeta potential -28.8±2.7 mV and cumulative release of MRN was ~72% over 24 hrs. The intracellular uptake of nanoparticles and cell viability was studied in H9c2 cells treated with AT1-MRN-HSA-NPs vs the control non-targeted drug, MRN Lactate under normal, hypoxic and hypertrophic conditions. The uptake of AT1-HSA-MRN-NPs in H9c2 cells was significantly higher as compared to non-targeted nanoparticles, and the viability of H9c2 cells treated with AT1-MRN-HSA-NPs vs MRN Lactate was 73.4±1.4% vs 44.9±1.4%, respectively. Therefore, AT1-HSA-MRN-NPs are safe for in vivo use and exhibit superior targeting and drug delivery characteristics for treatment of heart failure.


2021 ◽  
Author(s):  
Satya Prakash ◽  
Nikita Lomis ◽  
Susan Westfall ◽  
Dominique Shum-Tim

Congestive heart failure, a prominent cardiovascular disease results primarily from myocardial infarction or ischemia. Milrinone (MRN), a widely used clinical drug for heart failure, improves myocardial contractility and cardiac function through its inotropic and vasodilatory effects. However, lacking target specificty, it exhibits low bioavailability and lower body retention time. Therefore, in this study, angiotensin II (AT1) peptide conjugated human serum albumin nanoparticles (AT1-HSA-MRN-NPs) have been synthesized for targeted delivery of MRN to the myocardium, overexpressing AT1 receptors under heart failure. The NPs were surface functionalized through a covalent conjugation reaction between HSA and AT1. Nanoparticle size was 215.2±4.7 nm and zeta potential -28.8±2.7 mV and cumulative release of MRN was ~72% over 24 hrs. The intracellular uptake of nanoparticles and cell viability was studied in H9c2 cells treated with AT1-MRN-HSA-NPs vs the control non-targeted drug, MRN Lactate under normal, hypoxic and hypertrophic conditions. The uptake of AT1-HSA-MRN-NPs in H9c2 cells was significantly higher as compared to non-targeted nanoparticles, and the viability of H9c2 cells treated with AT1-MRN-HSA-NPs vs MRN Lactate was 73.4±1.4% vs 44.9±1.4%, respectively. Therefore, AT1-HSA-MRN-NPs are safe for in vivo use and exhibit superior targeting and drug delivery characteristics for treatment of heart failure.


2021 ◽  
Vol 28 ◽  
Author(s):  
Zhenyu Chen ◽  
Zhongling Luo ◽  
Jiayao Lyu ◽  
Jianxin Wang ◽  
Zhongbing Liu ◽  
...  

Background: Methotrexate (MTX) is the representative drug among the disease-modifying anti-rheumatic drugs. But the conventional treatment with MTX showed many limitations and side effects. Objective: To strengthen the targeting ability and circulation time of MTX in the treatment of rheumatoid arthritis, the present study focused on developing a novel drug delivery system of methotrexate-loaded human serum albumin nanoparticles (MTX-NPs) modified by mannose, which referred as MTX-M-NPs. Methods: Firstly, mannose-derived carboxylic acid was synthesized and further modified on the surface of MTX-NPs to prepare MTX-M-NPs. The formulation of nanoparticles was optimized by method of central composite design (CCD), with the drug lipid ratio, oil-aqueous ratio, and cholesterol or lecithin weight as the independent variables. The average particle size and encapsulation efficiency were the response variables. Response of different formulations was calculated and the response surface diagram, contour diagram and mathematical equation were used to relate the dependent and independent variables to predict the optimal formula ratio. The uptake of MTX-M-NPs by neutrophils was studied through the laser confocal detection. Further, MTX-M-NPs was subjected to assess the pharmacokinetics profile after intravenous injection with Sprague-Dawley rats. Results: This targeting drug delivery system was successfully developed. Results from Nuclear Magnetic Resonance and Fourier Transform Infrared Spectroscopy analysis can verify the successful preparation of this drug delivery system. Based on the optimized formula, MTX-M-NPs was prepared with a particle size of 188.17 ± 1.71 nm and an encapsulation rate of 95.55 ± 0.33%. MTX-M-NPs displayed significantly higher cellular uptake than MTX-NPs. The pharmacokinetic results showed that MTX-M-NPs could prolong the in vivo circulation time of MTX. Conclusion: This targeting drug delivery system laid a promising foundation for the treatment of RA.


2019 ◽  
Vol 7 (12) ◽  
pp. 5270-5282 ◽  
Author(s):  
Yuxin Wang ◽  
Diya Xie ◽  
Jiongru Pan ◽  
Chengwan Xia ◽  
Lei Fan ◽  
...  

To ensure site–specific drug release in tumor cells and cancer-associated fibroblasts and reduce the systemic toxicity of chemotherapy, a novel drug delivery system called human serum albumin-indocyanine green-cisplatin nanoparticles was developed.


Nanoscale ◽  
2016 ◽  
Vol 8 (7) ◽  
pp. 3991-4000 ◽  
Author(s):  
Fu Wang ◽  
Kai Yang ◽  
Zhe Wang ◽  
Ying Ma ◽  
J. Silvio Gutkind ◽  
...  

This integrated imaging platform could provide more reliable respective PK profiles of a loaded drug and its carrier.


Nanomaterials ◽  
2016 ◽  
Vol 6 (6) ◽  
pp. 116 ◽  
Author(s):  
Nikita Lomis ◽  
Susan Westfall ◽  
Leila Farahdel ◽  
Meenakshi Malhotra ◽  
Dominique Shum-Tim ◽  
...  

2019 ◽  
Vol 129 ◽  
pp. 267-280 ◽  
Author(s):  
Vieri Piazzini ◽  
Elisa Landucci ◽  
Mario D'Ambrosio ◽  
Laura Tiozzo Fasiolo ◽  
Lorenzo Cinci ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document