Optimization of carboxylate-terminated poly(amidoamine) dendrimer-mediated cisplatin formulation.
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.
IICT-RMIT Research Centre .
Hitesh
H
Kulhari
Deep
D
Pooja
Mayank K
MK
Singh
Abhay S
AS
Chauhan
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry*; D050091:Dendrimers / Q000008:administration & dosage* / Q000737:chemistry*; D016503:Drug Delivery Systems; D004355:Drug Stability; D005029:Ethylenediamines / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques
D000970:Antineoplastic Agents; D050091:Dendrimers; D005029:Ethylenediamines; C104700:PAMAM Starburst; C031234:ethylenediamine; D002945:Cisplatin
Cisplatin; encapsulation; formulation; optimization; poly(amidoamine) dendrimer