Faculty Collaboration Database

Optimization of carboxylate-terminated poly(amidoamine) dendrimer-mediated cisplatin formulation. Drug Dev Ind Pharm 2015 Feb;41(2):232-8

Date

11/19/2013

Pubmed ID

24237325

DOI

10.3109/03639045.2013.858735

Scopus ID

2-s2.0-84921917836 (requires institutional sign-in at Scopus site)   47 Citations

Abstract

Abstract Cisplatin is mainly used in the treatment of ovarian, head and neck and testicular cancer. Poor solubility and non-specific interactions causes hurdles in the development of successful cisplatin formulation. There were few reports on poly(amidoamine) (PAMAM) dendrimer-cisplatin complexes for anticancer treatment. But the earlier research was mainly focused on therapeutic effect of PAMAM dendrimer-cisplatin complex, with less attention paid on the formulation development of these complexes. Objective of the present study is to optimize and validate the carboxylate-terminated, EDA core PAMAM dendrimer-based cisplatin formulation with respect to various variables such as dendrimer core, generation, drug entrapment, purification, yield, reproducibility, stability, storage and in-vitro release. Dendrimer-cisplatin complex was prepared by an efficient method which significantly increases the % platinum (Pt) content along with the product yield. Dendrimers showed reproducible (∼27%) platinum loading by weight. Variation in core and generations does not produce significant change in the % Pt content. Percentage Pt content of dendrimeric formulation increases with increase in drug/dendrimer mole ratio. Formulation with low drug/dendrimer mole ratio showed delayed release compared to the higher drug/dendrimer mole ratio; these dendrimer formulations are stable in room temperature. In vitro release profiles of the stored dendrimer-cisplatin samples showed comparatively slow release of cisplatin, which may be due to formation of strong bond between cisplatin and dendrimer. This study will contribute to create a fine print for the formulation development of PAMAM dendrimer-cisplatin complexes.

Author List

Kulhari H, Pooja D, Singh MK, Chauhan AS

Author

Abhay Chauhan PhD Associate Professor in the School of Pharmacy Administration department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antineoplastic Agents
Chemistry, Pharmaceutical
Cisplatin
Dendrimers
Drug Delivery Systems
Drug Stability
Ethylenediamines
Humans
In Vitro Techniques