Investigations on cellular interaction of polyelectrolyte based nano-walled reservoir using MCF-7 cell lines: a novel chemotherapeutic approach.
OBJECTIVE
A polyelectrolyte (PE) based nano-walled reservoir (NwR) was developed using alternate deposition of natural polyions on a decomposable core (CaCO(3)). The system was charged with paclitaxel (PTX) using the trigger property of an organic solvent (NwR-PTX). In addition, the surface of the nano-walled reservoir was modified with PE-PEG2000 (NwR-PTX-PEG)) in order to investigate any changes in the interaction of surface-modified polyelectrolyte shells with breast cancer cells, since surface chemistry greatly influences the performance of microcapsules in the biological environment.


METHODS
The surface modification was confirmed by differential scanning calorimetry studies, which showed a shifting of the endothermic peak after pegylation. Layer-by-layer (LBL) growth of the system was confirmed by the sequential change in the zeta-potential. The release of paclitaxel from the formulations followed first order kinetics (r(2) = 0.9), indicating matrix diffusion. The interaction of NwR-PTX with MCF-7 cell lines was investigated by coating the system with FITC-dextran (NwR-PTX-FITC) and quantitated using flow cytometry.


RESULTS
Cellular uptake of positively charged NwR reached 56% after 4 h and 76% after 24 h. This was reduced significantly after pegylation. The negatively charged NwR reached only 49% after 24 h.


CONCLUSIONS
This study opens the possibility of specific targeting of tumour cells that can control the release of chemotherapeutic agent either by means of a physiological or chemical trigger. This suggests potential application of this system as a novel approach for the delivery of chemotherapeutic agents.
Gupta
Girish K
GK
Pharmaceutics Division, Central Drug Research Institute, Lucknow (CSIR), India.
Gupta
Vivek K
VK
Shukla
Prashant
P
Pant
Aditya B
AB
Mishra
Prabhat R
PR
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000627:therapeutic use; D001692:Biological Transport; D001943:Breast Neoplasms / Q000188:drug therapy*; D002214:Capsules / Q000737:chemistry; D045744:Cell Line, Tumor; D003911:Dextrans / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004573:Electrolytes / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D049329:Nanostructures / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry* / Q000627:therapeutic use; D055672:Static Electricity
D000972:Antineoplastic Agents, Phytogenic; D002214:Capsules; D003911:Dextrans; D004337:Drug Carriers; D004573:Electrolytes; D017239:Paclitaxel