Co-axial electrospraying of injectable multi-cancer drugs nanocapsules with polymer shells for targeting aggressive breast cancers

Mujibur Khan,Mohammad Rashid,Raziye Piranlioglu,Ahmet Alptekin,Md. Mahmudul Hasan,Anne Barnett,Ali Arbab

doi:10.1186/s12645-022-00114-1

Abstract

BackgroundThere is growing potential for nanocarrier-based drug delivery in cancer. However, an incomplete understanding of nano–bio interactions and the challenges regarding processing and fabrication in scale-up engineering techniques, controls over drug release, efficacy, and cytotoxicity to the human cell are the major challenges for its clinical success. The purpose of the study was to develop an electrospraying processing of injectable nanonized encapsulated chemotherapeutics to target primary and metastatic breast cancer tumor microenvironment for precise and controlled delivery.ResultsA novel coaxial electrospraying of multiple cancer drugs (paclitaxel and GW2580) as core and polycaprolactam (PCL) as the shell has been developed to produce multi-cancer drug nanocapsules. Using electrospraying process, we have successfully made nanocapsules containing paclitaxel to target breast cancer cells and GW2580, a colony-stimulating factor 1 receptor (CSF1R) inhibitor to target CSF1R+ myeloid cells in the tumor microenvironments (TME). The UV–vis drug release test for 14 days shows a prolonged and sustained release pattern of both the drugs. In vitro and in vivo results showed the effects of nanocapsules containing multiple drugs in controlling the growth of tumor cells and increased survival of the animal bearing breast cancers.ConclusionNanonized multi-cancer drugs were encapsulated in a PCL shell. The drug doses ratio and the polymer-to-drug ratio were controlled by engineered process parameters. The studies showed the importance of making nanocapsules containing nanocrystals of multiple drugs, which will pave the way of making multiple drug combinations in a controlled manner and capsules can be designed for sustained release of the drugs after accumulation into the TME. TME-directed therapy can be a norm in future cancer treatment strategies. These injectable nanocapsules will allow cancer site-specific precision and controlled delivery to cure primary and metastatic breast cancer and to overcome the chemotherapy resistance.

Highlights

There is growing potential for nanomedicine as effective, safer, and targeted cancer treatment with the recent advancement
Samples were electrosprayed with a voltage between 40 and 45 kV directly on TEM grids made of lacey carbon copper
In vivo results proved our hypothesis that nanocapsules containing multiple drugs will accumulate and release

Summary

Introduction

There is growing potential for nanomedicine as effective, safer, and targeted cancer treatment with the recent advancement. An incomplete understanding of nano–bio interactions and the challenges regarding processing and fabrication in scale-up engineering techniques, controls over drug release, efficacy, and cytotoxicity to the human cell are the major challenges for its clinical success (Shi et al 2017). Au NPs have low colloidal stability in blood flow and high toxicity towards human cell impeding its use as nanocarrier in cancer therapy (Voura et al 2004). Functionalized superparamagnetic iron oxide nanoparticles (SPIONs) containing magnetite (Fe3O4) and maghemite (Fe2O3) were proposed as targeted drug delivery. There is growing potential for nanocarrier-based drug delivery in cancer. An incomplete understanding of nano–bio interactions and the challenges regarding processing and fabrication in scale-up engineering techniques, controls over drug release, efficacy, and cytotoxicity to the human cell are the major challenges for its clinical success. The purpose of the study was to develop an electrospraying processing of injectable nanonized encapsulated chemotherapeutics to target primary and metastatic breast cancer tumor microenvironment for precise and controlled delivery

Objectives

Results

Conclusion