Glucosamine-anchored doxorubicin-loaded targeted nano-niosomes: pharmacokinetic, toxicity and pharmacodynamic
Smita Pawar1, Ganesh Shevalkar1, Pradeep Vavia1
1a Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology , Elite Status and Center of Excellence - Govt. of Maharashtra , Mumbai , Maharashtra , India.
Background:
Efficacy of anticancer drug is limited due to non-selectivity and toxicities allied with the drug; therefore the heart of the present work is to formulate drug delivery systems targeted selectively towards cancer cells with minimal toxicity to normal cells.
Purpose:
Targeted drug delivery system of doxorubicin (DOX)-loaded niosomes using synthesized N-lauryl glucosamine (NLG) as a targeting ligand.
Methods:
NLG-anchored DOX niosomes were developed using ethanol injection method.
Results:
Developed niosomes had particle size <150 nm and high entrapment efficiency ∼90%. In vivo pharmacokinetics exhibited long circulating nature of targeted niosomes with improved bioavailability, which significantly reduced CL and Vd than DOX solution and non-targeted niosomes (35 fold and 2.5 fold, respectively). Tissue-distribution study and enzymatic assays revealed higher concentration of DOX solution in heart while no toxicity to major organs with developed targeted niosomes was observed. Solid skin melanoma tumor model in mice manifested the commendable targeting potential of targeted niosomes with significant reduction in tumor volume and high % survival rate without drop in body weight in comparison with DOX solution and non-targeted niosomes of DOX.
Conclusion:
The glucosamine-anchored DOX-loaded targeted niosomes showed its potential in cancer targeted drug therapy with reduced toxicity. Abbreviations ALT alanine transaminase CL clearance CPK creatinine phosphokinase DOX doxorubicin EDC.HCL ethyl carbidimide hydrochloride GLUT glucose transporter GSH glutathione S-transferase LDH lactate dehydrogenase LHRH luteinizing hormone-releasing hormone MDA malonaldehyde NHS N-hydroxy succinimide NLG N-lauryl glucosamine NTAR DoxNio non-targeted doxorubicin niosomes PBS phosphate buffer saline RGD argynyl glycyl aspartic acid SGOT serum glutamate oxaloacetate transaminase SGPT serum glutamate pyruvate transaminase SOD superoxide dismutase TAR DoxNio targeted doxorubicin niosomes Vd volume of distribution.
Insights
Targeted doxorubicin (DOX) niosomes using N-lauryl glucosamine (NLG) demonstrated enhanced cancer therapy with reduced toxicity. These targeted niosomes improved bioavailability and significantly reduced tumor volume in a melanoma model.
Area of Science:
- Nanotechnology
- Pharmacology
- Oncology
Background:
- Anticancer drug efficacy is limited by non-selectivity and toxicity.
- Developing targeted drug delivery systems is crucial for minimizing harm to normal cells.
Purpose of the Study:
- To formulate doxorubicin (DOX)-loaded niosomes utilizing N-lauryl glucosamine (NLG) as a targeting ligand for selective cancer cell delivery.
- To evaluate the efficacy and safety of NLG-anchored DOX niosomes in a preclinical cancer model.
Main Methods:
- NLG-anchored DOX niosomes were prepared using the ethanol injection method.
- Characterization included particle size analysis and entrapment efficiency determination.
- In vivo studies involved pharmacokinetics, tissue distribution, and efficacy assessment in a solid skin melanoma tumor model in mice.
Main Results:
- The developed niosomes exhibited a particle size below 150 nm and high entrapment efficiency (~90%).
- Targeted niosomes demonstrated prolonged circulation, improved bioavailability, and significantly reduced clearance and volume of distribution compared to free DOX.
- Significant tumor volume reduction and a high survival rate were observed in the targeted niosome group, with no observed toxicity in major organs.
Conclusions:
- Glucosamine-anchored DOX-loaded targeted niosomes show significant potential for targeted cancer therapy.
- This approach effectively reduces drug toxicity while enhancing therapeutic outcomes.
- Targeted niosomes represent a promising strategy for improving the safety and efficacy of chemotherapy.
