ACUTE TOXICOLOGICAL INVESTIGATION OF POLYETHYLENE GLYCOL DERIVATIZED FOURTH AND FIFTH GENERATION POLY (PROPYLENEIMINE) DENDRIMERS

NITIN DWIVEDI; DUSHYANT KUMAR PARMAR; PRASHANT KESHARWANI; JIGNA SHAH

doi:10.22159/ijap.2019v11i5.34203

Authors

NITIN DWIVEDI Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, 382481, India
DUSHYANT KUMAR PARMAR Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, 382481, India
PRASHANT KESHARWANI Department of Pharmaceutics, Institute of Pharmacy, Jamia Millia Islamia Central University, New Delhi, Delhi 110025, India
JIGNA SHAH Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, 382481, India

DOI:

https://doi.org/10.22159/ijap.2019v11i5.34203

Keywords:

Poly (propyleneimine) Dendrimers, Generation, Toxicity of Dendrimers, Biocompatibility, Drug Loading

Abstract

Objective: The aim of the present study leads a comparative assessment of the toxicological profile of PEGylated fourth and fifth-generation poly (propylene imine) dendrimers (PPI).

Methods: 4.0G and 5.0G generations of PPI dendrimer were synthesized and PEGylated with Mono polyethylene glycol 5000 (MPEG-5000). Each PEGylated 4.0G and 5.0G dendrimeric generation were administered in three different doses: 2.5 mg/kg, 25 mg/kg and 250 mg/kg (i.e., low, intermediate and high dose) to wister rats. After the dose administration, the blood and tissue samples of wister rats were collected after 24 h and 15 d after. All the collected samples were proceeded for hematological, biochemical and histopathological studies.

Results: After 24 h of (250 mg/kg) dose administration PEGylated 5.0G PPI dendrimer the RBC count, hemoglobin content and WBC count were found 7.873±0.129 mill/cmm, 13.833±0.491g/dl and 9033.33±2384.906 mill/cmm, while PEGylated 4.0G PPI dendrimer indicated RBC count, hemoglobin content and WBC count 8.733±0.239 mill/cmm, 14.033±0.12 g/dl and 9666.667±2567.316 mill/cmm, in blood samples as compare to RBC count 9.346±0.037 mill/cmm, hemoglobin content 15.35±0.15 g/dl and WBC count 8500±286.675 mill/cmm of the animals of normal control group. Thus there are no remarkable changes (p>0.05) in RBC count, hemoglobin content and other hematological profile after 24 h in comparison of normal control group of animals. Similarily insignificant changes (p>0.05) in serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), lactate dehydrogenase (LDH) and sections of different organs indicate inoffensive nature of both generations of PEGylated 4.0G and 5.0 G PPI dendrimers.

Conclusion: It can be concluded that fifth-generation PPI dendrimers are more suitable as compared to fourth generation of PPI dendrimer, while both dendrimers are not generating any severe toxicity.

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