Janus Nanoparticles Loaded 3D Bio Printed Scaffold as a Dual Drug Delivery System

Abstract

Herein, a new type of controlled-release system is fabricated using polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA) nanoparticles for the creation preparation study. They include doxorubicin (DOX), a standard chemical for chemotherapy, and curcumin, part of the plant turmeric. The material is produced as a dual-loaded nanoparticle system, where the widely used chemotherapeutic drug Doxorubicin (DOX) and the commonly known anti-inflammatory/antioxidant Curcumin are encapsulated in their respective phases, PCL and PLGA. Next, the Janus NPs were loaded into a 3D bioprinted support matrix composed solely of Carbopol. The design of this scaffold was engineered to provide a biocompatible and supportive environment for the controlled release of medication over an extended period. The biocompatibility, kinetics of drug release, and biomechanical properties were also analyzed in the 3D-printed scaffold. The structural integrity of the scaffold was strengthened, and DOX as well as curcumin can be continuously released for long periods by using Janus nanoparticles. Moreover, dual drug-loaded nanoparticles provided a sustained release plan that could be an innovative technique for improved anticancer activity in synergy therapy; the scaffold supported particle stability as indicated by favorable results of preliminary research. This system might offer a more potent and target-oriented strategy in cancer therapy through the sustained release of curcumin and DOX, effectively reducing cancer cell viability compared to conventional drug delivery approaches.

Introduction

Each year millions of new cases are identified, making cancer one of the most significant global health issues. Although significant strides have been made in the scientific understanding of cancer, treating it remains a daunting proposition fraught with the enervating attributes of conventional therapeutic modalities. Chemotherapy, one of the more common cancer treatments, has been effective in controlling or curing some cancers. However, its application might lead to severe side effects, including non-specific targeting, systemic toxicity, and resistance occurrence, which reduce the therapeutic effectiveness of this drug and increase patient morbidity. These challenges highlight an imminent need for more sophisticated precision and targeted drug delivery strategies to perpetuate treatment efficacy and ameliorate side effects. In the modern era, nanotechnology can offer solutions to these problems through the development of nanoparticle-based drug delivery systems. Not only does modifying nanoparticles improve a drug’s solubility, stability, and bioavailability, but it also better directs the medication to cancerous regions. Janus NPs have one of the most unique biphasic structures, making them an interesting subset among other NP types. These nanoparticles have opposite top and bottom surfaces to which different functionalities can be added. Named after the two-faced Roman god Janus, their structural flexibility provides an attractive option for combinational cancer therapy by carrying multiple therapeutic drugs with diverse physicochemical properties and modes of action.

A novel drug delivery system is developed, fabricated, and described in this study, using polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA) nanoparticles. Due to their biocompatibility, tunable degradation rates, and ability to encapsulate a broad range of therapeutic agents, PCL and PLGA have been extensively studied for drug delivery applications. In this system, the Janus nanoparticles have dual therapeutic components with different and complementary anticancer activities: curcumin (CUR) and doxorubicin (DOX). The turmeric plant produces a polyphenol known as curcumin, which has long been notable for its anti-inflammatory, antioxidant, and antimicrobial effects. It has been shown to induce apoptosis, inhibit cancer cell proliferation, and enhance the effects of other chemotherapeutic drugs. However, the application of curcumin has been limited due to its poor solubility in water and susceptibility to degradation. In contrast, doxorubicin (DOX) is a widely used chemotherapeutic drug effective against various malignancies but is associated with severe adverse effects, including cardiotoxicity. To address the limitations of each therapeutic agent, DOX is encapsulated into PLGA, and curcumin is loaded onto PCL within the Janus nanoparticles, creating a dual-agent system with different mechanisms of action. This system is further enhanced by integrating these Janus nanoparticles into a 3D bioprinted scaffold matrix composed solely of Carbopol, which provides a biocompatible and supportive environment for the controlled release of encapsulated drugs. Carbopol, a synthetic polymer, is well-known for its stability and gel-forming properties, making it an ideal material for this scaffold.

The present study details the mechanical behavior, biocompatibility, and drug release kinetics of this 3D bioprinted scaffold. Due to the higher stability of the scaffold combined with Janus nanoparticles, curcumin, and DOX can diffuse out steadily onto a solid substrate. The drug release profile was sequential, with DOX following curcumin. This sequential release is beneficial for synergistic cancer therapy since curcumin can sensitize the effect of DOX in killing cancer cells, potentially contributing to a more substantial therapeutic outcome. The study suggests that the scaffold enabled a controlled and prolonged release of curcumin as well as DOX. Furthermore, the results of this study suggest that an approach using a Janus-nanoparticle-based dual payload on 3D bio-printed scaffolds may lead to a long-term reduction in cancer cell viability by releasing drugs over extended periods, potentially offering a more targeted and efficient strategy compared with traditional drug delivery methods. The findings of this study provide insights into how this innovative drug delivery method may help overcome limitations associated with existing cancer therapies, bringing researchers closer to more personalized and definitive clinical strategies. This study offers a comprehensive overview of the original combination of Janus nanoparticles and 3D-printed drug delivery systems, highlighting its potential to enhance treatment efficacy and improve the quality of life for cancer patients by overcoming major challenges in anticancer therapy, including drug solubilization, protection from degradation before entering blood circulation, and specific targeting.”

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Mahinour Elmowafy, Samir El-Mashtoly, Ahmed Khalil, Amr Nassrallah, Janus Nanoparticles Loaded 3D Bio Printed Scaffold as a Dual Drug Delivery System, The Eurasia Proceedings of Health, Environment and Life Sciences (EPHELS), ISSN: 2791-8033, The Eurasia Proceedings of Health, Environment and Life Sciences (EPHELS), 2024, Volume 16, Pages 11-17, International Conference on Medical and Health Sciences (ICMeHeS), November 14-17, 2024, Antalya/Turkey

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