Send Orders for Reprints to reprints@benthamscience.net Drug Delivery Letters, 2019, 9, 000-000 1 RESEARCH ARTICLE 2210-3031/19 $58.00+.00 © 2019 Bentham Science Publishers Synthesis, Characterization and in vivo Evaluation of PEGylated PPI Dendrimer for Safe and Prolonged Delivery of Insulin Ashish K. Parashar 1,2 , Preeti Patel 3 , Arun K. Gupta 1 , Neetesh K. Jain 4 and Balak Das Kurmi 3,* 1 Pharmaceutics Research Laboratory, Chameli Devi Institute of Pharmacy, Indore 452020 India; 2 Pharmaceutics Re- search Laboratory, Department of Pharmaceutical Sciences, Dr. H.S. Gour University, Sagar, MP 470003, India; 3 Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilaspur 495009, India; 4 Department of Phar- macy, Oriental University, Indore -452001 India A R T I C L E H I S T O R Y Received: January 23, 2019 Revised: March 04, 2019 Accepted: March 06, 2019 DOI: 10.2174/2210303109666190401231920 Abstract: Objective: The present study was aimed at developing and exploring the use of PEGylated Poly (propyleneimine) dendrimers for the delivery of an anti-diabetic drug, insulin. Methods: For this study, 4.0G PPI dendrimer was synthesized by successive Michael addition and ex- haustive amidation reactions, using ethylenediamine as the core and acrylonitrile as the propagating agent. Two different activated PEG moieties were employed for PEGylation of PPI dendrimers. Vari- ous physicochemical and physiological parameters UV, IR, NMR, TEM, DSC, drug entrapment, drug release, hemolytic toxicity and blood glucose level studies of both PEGylated and non- PEGylated den- dritic systems were determined and compared. Results: PEGylation of PPI dendrimers caused increased solubilization of insulin in the dendritic framework as well as in PEG layers, reduced drug release and hemolytic toxicity as well as increased therapeutic efficacy with reduced side effects of insulin. These systems were found to be suitable for sustained delivery of insulin by in vitro and blood glucose-level studies in albino rats, without produc- ing any significant hematological disturbances. Conclusion: Thus, surface modification of PPI dendrimers with PEG molecules has been found to be a suitable approach to utilize it as a safe and effective nano-carrier for drug delivery. Keywords: Dendrimer (s), PEGylation, insulin, drug delivery systems, disease state(s), diabetes. 1. INTRODUCTION Dendrimers are synthetic monodispersed macromolecules with regular and highly branched three-dimensional polym- eric architectures that have generated tremendous interest in the field of drug delivery [1]. These are well defined, three- dimensional macromolecules that radiate from a central core and are synthesized through a stepwise, repetitive reaction sequence that guarantees complete shells for each genera- tion, leading to polymers that are monodispersed [2]. Den- drimers are a new class of structurally perfect architecture having unique properties (electronic, optical, opto-electronic, magnetic, chemical, and biological) with exceptional fea- tures such as nanometric size, container properties, high de- gree of structural symmetry, a density gradient and large number of peripheral functional groups, which make them attractive drug carriers [3]. These are also known as starburst [4] or cascade [5] or molecular tree [6] or arborols [7], or *Address correspondence to this author at the Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilaspur 495009, India; E-mail: bdkurmi@gmail.com polymers, etc. One more vital characteristic of dendritic molecules is their high solubility in water as well as in a large number of organic solvents, which offers superior process proficiency characteristics. The function of the den- dritic box as a host for a variety of guest molecules also has an impact on the delivery of chemotherapeutics in pharma- ceutical research [8]. Prolonged residence time of the drug in the blood circulatory system and protection of the bioactives from its environment with increased stability are some other potential advantages of dendrimeric architecture [9]. Several research groups have explored the overwhelming potential of dendrimers as advanced materials in many different areas including medicine and catalysis, among others. Particularly, the use of dendrimers as drug delivery vehicles has attracted much attention among the various available dendrimers. A massive work has been repeated with polyamidoamine (PAMAM) and poly (propyleneimine) (PPI) dendrimer in recent years [10]. The advantages associated with the PPI dendrimers such as regular size and shape, a larger number of readily accessible end groups, either nitrile or amine, the possibility of end group modification, polyelectrolyte charac- ter, and the possibility of encapsulating guest molecules