Nanoparticle Drug Delivery System for Chemotherapy

Contents

Introduction

Overview of Chemotherapy and Its Challenges: chemotherapy is the process of using chemical agents to destroy rapidly dividing cells in cancer. Cancer is the leading cause of death with a staggering rate of 10 million deaths annually. There are several chemotherapeutic agents such as alkylating agents, antimetabolites, topoisomerase inhibitors, mitotic inhibitors etc. However, challenges associated with chemotherapy are the lack of site-specific drug delivery, side effects associated with it leading to severe patient discomfort. An ideal cancer therapy targets the cancer cells with minimal side effects.
The Role of Nanoparticles in Modern Medicine: the nanoparticles are utilized in medicine to provide targeted drug delivery to cells or tissues for therapeutic effects. Since larger drug molecules cannot reach target sites, researchers use nanotechnology to deliver nanosized drugs. In modern medicine, nanoparticles are used in targeted drug delivery, diagnostic imaging (as contrasting agents), gene therapy, regenerative medicine, theragnostic and many more. In this article we discuss nanoparticle drug delivery systems for chemotherapy.

What Are Nanoparticles? Nanoparticles in medicine function as NanoSystems for diagnostics or deliver minute quantities of medicine to the target site in a controlled manner to produce the desired pharmacological effect. Nanoparticles provide site specific, accurate delivery of drugs.
Types of Nanoparticles Used in Drug Delivery: nanoparticles are of different types based on their unique properties and applications:

Polymeric Nanoparticles: biodegradable polymers that are used in sustained drug release. Eg: Chitosan, Alginate, Xanthan gum.
Lipid-based polymers: Lipid based, similar to cell membranes that are used in hydrophobic drug delivery with improved solubility.
Inorganic Nanoparticles: inorganic materials are used in imaging and as carriers for drug delivery due to magnetic and optical properties. Eg: silica, gold.
Dendrimers: highly branched, 3D structures that are suitable for simultaneously delivering multiple drugs or therapeutic agents. Eg: PAMAM, PPI, liquid crystalline, core–shell, chiral, peptide, glycodendrimers and PAMAMOS.
Nanocrystals: pure drug solid particle of size 1000 nm.
Quantum dots: semiconductor nanocrystals.
Proteins and polysaccharide nanoparticles: natural biopolymers from plants, animals, and microorganisms.

Enhanced Targeting of Cancer Cells: Researchers consider nanoparticles for targeted delivery with minimal side effects. As an alternative, they are developing smart nanoparticles that provide site-specific drug delivery with a triggered stimulus. The smart nanoparticles aggregate at the target site to co-deliver the precise dose of drugs and diagnostic agents making them an ideal theragnostic. Smart nanoparticles have tumor-targeting characteristics by making tumor specific ligands (antibodies, aptamers, etc.) on its surface
Reduced Side Effects and Toxicity: targeted drug delivery by the nanoparticles provides site specific availability of the drugs thereby preventing toxic effects and side effects due to availability at non-target sites. Furthermore, controlled delivery of specific dose of drug ensures that there is no side effects or lethal effects with larger dosing
Improved Drug Solubility and Stability: drug encapsulation within the nanoparticles provides more protection from degradation by enzymes that can increase bioavailability of the drug. Nanoparticles can provide high surface area to volume ratio, which enhances the dissolution rate of the poorly soluble drugs.

Two types of targeting:

Passive Targeting: The drug carrier complex in blood moves towards the target receptors based on affinity or binding, influenced by pH, molecular size, shape, and temperature, demonstrating the Enhanced Permeability and Retention (EPR) Effect in passive targeting.
Active Targeting: Ligand-Receptor Interactions in which the drug carrier system will carry the drugs to the receptors expressed at the target site.

Smart Nanoparticles: Computer-aided AI-powered smart nanoparticles have been proposed to provide target-specific drug delivery by aggregating to form a smart microenvironment, demonstrating greater potential in responding to the tumor microenvironment.

Combination Therapies Using Nanoparticles: combination of nanoparticles can enhance efficacy, and provide synergistic effects. Example: combination of chemotherapy and immunotherapy (doxorubicin liposomal, gold paclitaxel nanoparticles, etc)

Overcoming Biological Barriers: the challenge associated with nano drug delivery is crossing the biological barriers to reach the target site. The blood brain barrier (BBB) is a highly selective barrier that protects the brain. The nanoparticles must cross the BBB. Immune system can clear nanoparticles before reaching the target. Dense extracellular matrix and abnormal blood vessels of tumors can hinder penetration and distribution of nanoparticles.
Regulatory and Manufacturing Considerations: lack of standard protocols for manufacturing of nanoparticles to identify its toxicity, and lack of regulatory policies and guidelines that inhibits the clinical studies of nanoparticles.
Future Prospects and Research Directions: AI and machine learning integrations can optimize the nanoparticle drug delivery systems. Researchers are now focusing on the multifunctional capabilities of nanoparticles, such as theragnostic (treatment and diagnostics).

Nano therapy serves as an alternative to conventional chemotherapy by delivering drugs in a site-specific, controlled manner with minimal side effects. Integration of latest technologies provides a promising development in nano therapy. However, lack of standard protocols and regulations can be a barrier to its limitless potential in modern medicine.

Written By: Ayoob Mansoor, PharmD, RPh