A kNGR Peptide-Tethered Lipid-Polymer Hybrid Nanocarrier-Based Synergistic Approach for Effective Tumor Therapy: Development, Characterization, Ex-Vivo, and In-Vivo Assessment

被引:11
|
作者
Gupta, Madhu [1 ,2 ]
Sharma, Vikas [3 ]
Sharma, Kalicharan [1 ]
Kumar, Anoop [1 ]
Sharma, Ajay [1 ]
Kazmi, Imran [4 ]
Al-Abbasi, Fahad A. [4 ]
Alzarea, Sami, I [5 ]
Afzal, Obaid [6 ]
Altamimi, Abdulmalik Saleh Alfawaz [6 ]
Singh, Sachin Kumar [7 ,8 ]
Gupta, Gaurav [9 ,10 ,11 ]
Paudel, Keshav Raj [12 ]
Hansbro, Philip M. [12 ]
Dua, Kamal [8 ,13 ]
机构
[1] Delhi Pharmaceut Sci & Res Univ, Dept Pharmaceut, Pushp Vihar Sect 3,MB Rd, New Delhi 110017, India
[2] Dr HS Gour Univ Cent Univ, Dept Pharmaceut Sci, Drug Delivery Res Lab, Sagar 470003, India
[3] Divine Int Grp Inst Pharm, Gwalior 474001, Madhya Pradesh, India
[4] King Abdulaziz Univ, Fac Sci, Dept Biochem, Jeddah 21589, Saudi Arabia
[5] Jouf Univ, Coll Pharm, Dept Pharmacol, Sakaka 72388, Saudi Arabia
[6] Prince Sattam Bin Abdulaziz Univ, Coll Pharm, Dept Pharmaceut Chem, Al Kharj 11942, Saudi Arabia
[7] Lovely Profess Univ, Sch Pharmaceut Sci, Phagwara 144411, India
[8] Univ Technol Sydney, Fac Hlth, Australian Res Ctr Complementary & Integrat Med, Ultimo 2007, Australia
[9] Suresh Gyan Vihar Univ, Sch Pharm, Mahal Rd, Jaipur 302017, Rajasthan, India
[10] Saveetha Univ, Saveetha Dent Coll, Saveetha Inst Med & Tech Sci, Dept Pharmacol, Chennai 602105, Tamil Nadu, India
[11] Uttaranchal Univ, Uttaranchal Inst Pharmaceut Sci, Dehra Dun 248007, Uttarakhand, India
[12] Centenary Inst & Univ Technol Sydney, Fac Sci, Ctr Inflammat, Sch Life Sci, Sydney, NSW 2007, Australia
[13] Univ Technol Sydney, Grad Sch Hlth, Discipline Pharm, Sydney, NSW 2007, Australia
基金
英国医学研究理事会;
关键词
kNGR peptide; hybrid nanoparticles; targeted therapy; intracellular delivery; polymer-lipid CD13 receptor; AMINOPEPTIDASE N; NANOPARTICLES; PACLITAXEL; DELIVERY; DOXORUBICIN; MICELLES; CONJUGATE; STRATEGY; BINDING; CARRIER;
D O I
10.3390/pharmaceutics14071401
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The present study aims to design, develop and characterize kNGR (Asn-Gly-Arg) peptide-conjugated lipid-polymer-based nanoparticles for the target-specific delivery of anticancer bioactive(s), i.e., Paclitaxel (PTX). The kNGR-PEG-DSPE conjugate was synthesized and characterized by using spectral analysis. The dual-targeted PLGA-lecithin-PEG core-shell nanoparticles (PLNs-kNGR-NPs) were synthesized using a modified nanoprecipitation process, and their physiological properties were determined. The results support that, compared to other NPs, PLNs-kNGR-NPs are highly cytotoxic, owing to higher apoptosis and intracellular uptake. The significance of rational nanoparticle design for synergistic treatment is shown by the higher tumor volume inhibition percentage rate (59.7%), compared to other designed formulations in Balb/c mice in the HT-1080 tumor-induced model. The overall results indicate that the PLNs-kNGR-NPs-based hybrid lipid-polymer nanoparticles present the highest therapeutic efficacy against solid tumor overexpressing the CD13 receptors.
引用
收藏
页数:18
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