Mr. Avinash Gothwal
Central University of Rajasthan, India.
Biography:
He is working on nano-architectured drug delivery systems for effective and targeted delivery of bio-actives against the frightened disorders i.e. cancer, AD and Parkinson. He has completed master’s degree in Medicinal and Pharmaceutical Chemistry in the year 2015 from Central university of Rajasthan, India.
Abstract:
Aims: According to an estimation of WHO by 2030 after every 33 seconds one will be diagnosed with AD (Alzheimer’s Disorder) which will lead to develop 1 million new cases per year [1]. Currently there is no treatment strategy which can reverse the process of neuro-degeneration. Consequently, achieving and maintaining high therapeutic doses in clinical practices is difficult due to selective permeability of blood brain barrier (BBB). It is therefore necessary to develop safe and effective approach, which can deliver bio-actives to brain for the effective treatment of several difficult to treat brain disorders.
Objective: The purpose of the present study is to develop and characterize polyamidoamine (PAMAM)-lactoferrin (PAMAM-Lf) conjugates for the effective delivery of anti-Alzheimer’s drug to brain across BBB.
Methodology: Lactoferrin (Lf) was chemically conjugated to (PAMAM) dendrimers. Conjugation was confirmed by FT-IR, 1H NMR, 2D-NMR spectroscopy and AFM techniques. Further, rivastigmine (RIV) was physically encapsulated to PAMAM (PAMAM-RIV) and PAMAM-Lf (PAMAM-Lf-RIV) conjugates. HPLC was used to quantify the drug loading and in vitro release was performed at physiological pH conditions. Brain targeting was also evaluated in animal model with additional behavioral studies.
Results and Discussion: Spectroscopic analysis confirmed the PAMAM-Lf conjugation, size of the conjugate was 100±3.1 nm after RIV loading and the size was increased up to 216±8.3 nm. AFM results showed the root mean square roughness (Rq) and surface roughness (Ra) are 6.31 and 5.27 nm, respectively. In vitro drug release from PAMAM-Lf-RIV conjugate was observed to be sustained and was evaluated for 100 h. Ex-vivo hemotoxicity of RIV loaded PAMAM-Lf conjugate was almost 9.8 fold lesser than the PAMAM dendrimer, 7.77 times lesser than PAMAM-RIV and 7.66 folds in comparison to naïve RIV. Bioavailability of the RIV was enhanced 7.63 folds compared to pure drug with other improved pharmacokinetic parameters. Exceptionally, the locomotor and object recognition behavior of the animals were also far improved over the naïve RIV and PAMAM-RIV which was a novel and significant change to address through this study.
Conclusion: PAMAM-Lf conjugate was developed to attain higher drug loading and effective delivery of RIV to brain. The obtained results were surprisingly in the area where very few studies with dendrimers are reported yet and it was observed that the behavioral response was improved with the delivery of RIV to brain using dendrimers. The developed dendrimeric system could be effective in brain delivery.
References: 1. 2015 Alzheimer’s disease Facts and Figures. Factsheet, Alzheimer’s Association.