Nano-carrier Based Smart Drug Delivery Systems Taking Aim At Cancer Therapy

By Author: Sidharth Mehta and Nikita Yadav
Total Articles: 4
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The creation of smart nanocarrier-based drug delivery systems, also known as Smart Drug Delivery Systems(SDDSs), was prompted by the nonspecific dispersion and unpredictable release of pharmaceuticals in Conventional Drug Delivery Systems (CDDSs). To lessen the adverse consequences associated with CDDSs, SDDSs can deliver medications to target locations with lower dose frequency and in a spatially controlled way. Chemotherapy is commonly used to treat cancer, the world's second most common cause of death. The SDDSs have sparked a lot of attention as a potential alternative to chemotherapy because of their site-specific drug delivery. SDDSs are interested in smart nanocarriers, which are nanoparticles that deliver drugs. Smart nanocarriers, targeting mechanisms, and stimulation strategies make up a smart drug delivery system.This review highlights the recent development of SDDSs for several smart nanocarriers, including liposomes, micelles, dendrimers, meso-porous silica nanoparticles, gold nanoparticles,carbon nanotubes, quantum dots, and hydrogels. Also, the challenges and future research scope in the field of SDDSs are also ...
... presented.

1. Introduction

Cancer is one of the leading causes of death but is surpassed by cardiovascular diseases. Chemotherapy plays a vital role in treating undetectable cancer micro-focuses and free cancer cells. Chemotherapy utilises chemical substances to kill or stop cancer cell development, regarding that cancer cells are developed often much faster than those are healthy ones, fast-developing cells are the main targeting of chemotherapy, but healthy cells are also rapidly growing, chemotherapy medications target those fast-growing healthy cells. By 2030, approximately 13.1 million cancer-related deaths have been predicted by the World Health Organisation (WHO). These situations are usually treated with traditional therapy, but this traditional approach has unwanted side effects on healthy body parts. Conventional drugs, due to their low specificity, cause serious toxicity in our bodies. These pharmaceuticals give low aqueous solubility and are less bioavailability and have less therapeutic benefit.Nanotechnology growth has a major influence on the treatment of cancer.

The selection of a suitable nanocarrier type follows the choice of the appropriate strategies to classify cancer cells. To identify cancer areas, SDDS uses the physiochemical differences between cancer and healthy cells. There are two main approaches to accurately identify the site of the cancer cell. To assess the cancer site indirectly, passive targeting uses an Enhanced Permeability (EPR) effect. Active targeting uses over-expressed cell surface receptor in cancer cells directly as a guided missile to kill cancer cells. The next step is to release drugs at a certain concentration at a certain location. Depending on the nature and smartness of the nanocarriers, drugs can be released from the nanocarriers by external or internal stimuli.The idea of these innovative therapies is either to block signals that help malignant cells grow and divide uncontrollably, to kill cancer cells by inducing apoptosis, to stimulate the immune system, or to target the delivery of chemotherapy agents specifically to cancer cells, to minimise the death of normal cells and to avoid undesirable side effects.

Conventional chemo-therapeutic substances are affected, both normal and tumor cells, that are distributed in a non-specific way across the body. Tissue selectiveness is an important question, given the possibility of advanced pharmacological agents. The dose within the solidtumor is consequently reduced, resulting in inadequate therapy owing to excessive toxicity. The ultimate objective regarding cancer therapy was to improve their patient’s survival duration and quality life by decreasing their systemic toxicity of chemotherapy.

The size of nanocarriers (10–400 nm) was suitable as a medication carrier because they had the benefits to have been able to carry big amounts of drugs, providing extended flow time (when surface PEGylated particularly) and selective facilitating tumor growth through the improved Effect Permeability and Retention (EPR). Nanocarriers could also be useful in the resolution of other conventional drug limitations, involving weak aqueous solubility, poor bioavailability, and undesirable drug pharmacokinetic characteristics. Additionally, transport through nanocarriers was revealed to resolve MDR (multidrug resistance) induced by drug efflux transporters like P-glycoprotein, which is often over-expressed in cells of cancer.

2. Smart Nanocarriers

Particles with at least one dimension on the order of 1 nm to 100 nm are popularly known as nanoparticles. Nanocarriers are nanoparticles that are utilised as transport modules for other drugs. Under external or internal stimulation, conventional nanocarriers are unable to transport and release drugs at the desired concentration at the targeted spot. As a result, traditional nanocarriers are not smart. To make them smart, they must be changed or functionalised. The following properties should be present in smart nanocarriers:

i. Smart nanocarriers should bypass the body's immune system's cleaning process,
ii. they should only accumulate at the intended location; and
iii. smart nanocarriers should release the cargo at the correct concentration at the targeted site under external or internal stimulation.

Eight promising nanocarriers(Fig. 1) are discussed in detail below:

2.1. Liposomes

Liposomes are spherical vesicles consisting of one or more bilayers of phospholipids that can be generated from cholesterol and natural or synthetic phospholipid. Lipophilic medicines embedded in lipid bilayers and hydrophilic materials in the interior aqueous compartment (Senapatiet al., 2018).

Stability, inappropriate drug loading, rapid drug release, and shorter blood circulation durations are only a few of the issues of conventional liposomes. To actively target the cancer site, monoclonal antibodies, antibody fragments, proteins, peptides, vitamins, carbohydrates, and glycoproteins are commonly grafted on the liposome(Noble et al., 2014). Liposomes have various advantages, including active group protection, cell-like membrane structure, minimal immunogenicity, biocompatibility, safety, efficacy, and increased half-life (Li et al., 2019). Based on nanotechnology, applications of liposome are the first pharmaceutical drug products that are approved for cancer and other therapeutic application. pH change, enzyme transformation, redox reaction, light, ultrasound, and microwaves are all examples of external and internal stimulations that smart liposomes respond to.

2.2. Micelles

Micelles has amphiphilic molecules that are arranged from a core of hydrophobic and hydrophilic corona. The interaction of hydrophobic/hydrophilic molecules control the structure of the micelles. The polar parts of the copolymer are attracted to the solvent when it is hydrophilic and its concentration beyond the critical micelle concentration (CMC), while the hydrophobic parts are directed away. In this way, the hydrophobic parts form a core, whereas the hydrophilic parts form a core. This type of arrangement is known as a direct or regular polymeric micelle. When amphiphilic molecules are exposed to a hydrophobic solvent, they produce a reverse micelle, which is a reverse structure(Shin et al., 2016).

Several advantages of micelles are like prolonged self-life, drug character not affected on drug delivery, etc. An appropriate size of micelles to allow the extravasation at the tumor site. Keet al., designed micelles loaded with both thioridazine —which has been reported to kill cancer stem cells— and doxorubicin, providing a promising strategy for breast-cancer treatment by targeting both cancer and cancer stem cells with this combination therapy