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Carbon Nanomaterial-Based Polymeric Nanocomposites for Drug … 185
Acknowledgements This work was supported by grants from the Natural Science Foundation of Heilongjiang Province of China (Grant Number LH2021B032) and Heilongjiang Provin­cial Universities Basal Research Foundation-Youth Innovation Talent Project (Grant Number
145109210).

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Carbon Nanomaterial-Incorporated Polysaccharide-Based Nanocomposite for Drug Delivery

Krishna Manjari Sahu, Kumar Panchajanya Nayak, and Sarat Kumar Swain
Abstract Drug delivery procedure assists in enhancing the efficacy and safety in
the administion of therapeutic agents. Certainly, selecting an efficacious drug admin­istration carrier is a significant challenge for researchers. Incorporating polysaccha­rides and carbon nanomaterials (CNs) in the synthesizing method of nanocomposites can offer a solution to overcome the obstacle of non-biodegradability and minimal biocompatibility properties, and low loading efficiencyand controlled and prolonged therapeutic administration affinity of the drug carrier system. The collaborating outcomes arising from the integration of CNs and polysaccharides are underscored, offering a nuanced understanding of their potential as therapeutic delivery vehicles. This chapter serves as a concise overview of the intricate interplay between CNs and polysaccharides, providing valuable insights for researchers and practitioners engaged in advancing nanomedicine for enhanced drug delivery applications.
Keywords Carbon nanomaterials delivery
· Chitosan · Cellulose · Hyaluronic acid · Drug
Abbreviations
1
HNMR1H nuclear magnetic resonance AFM Atomic force microscope ALG/al Alginate Apt Aptamer ATR-IR Attenuated Total Reflection-Infrared radiation BET Brunauer-Emmett-Teller CA Calcium alginate CA-CD Carbon dot coated alginate beads CLSM Confocal laser scanning microscopy
K. M. Sahu · K. Panchajanya Nayak · S. K. Swain (B) Veer Surendra Sai University of Technology, Burla, Sambalpur 768018, India e-mail: skswain_chem@vssut.ac.in
189
190 K. M. Sahu et al.
CMC CMC
Carboxymethyl cellulose
1
Carboxymethyl chitosan
2
CMS Carboxymethyl starch CUR/cur: Curcumin DCA Deoxycholic acid DLS Dynamic light scanning DSC Differential scanning calorimetry DSPE Distearoylphosphatidylethanolamine EDS Energy dispersive spectroscopy EDX Energy dispersive X-ray EPI Epirubicin FCM Flow cytometric analyses FESEM Field emission scanning electron microscopy FI Fluorescein isothiocyanate FTIR Fourier-transform infrared spectroscopy GCN Graphitic carbon nitride Gl Glucose GNS Graphene nanosheets HA
1
Hydroxyapatite HPCHS Hydropropyl chitosan HPLC High-Performance Liquid Chromatography IBU Ibuprofen IONP Iron oxide nanoparticle MG Magnetic graphene oxide MOFs Metal–organic frameworks mPEG Methoxy polyethylene glycol amine NAP Naproxen N-CQDs Nitrogen-doped carbon quantum dots OAL Oxidized sodium alginate PL Photoluminescence PNIPAM Poly(N-isopropylacrylamide) PVA Poly vinyl alcohol QC Quercetin SA Sodium alginate SEM Scanning electron microscope SWNH Single-walled carbon nanohorns TEM Transmission electron microscopy TEM Transmission electron microscope TGA Thermogravimetric analysis TPP Tripolyphosphate UV-Vis UV–Visible spectroscopy VSM Vibrating sample magnetometer XPS X-ray photoelectron spectroscopy XRD X-ray diffraction pattern β-TC Tetracycline associated with β-cyclodextrin
Carbon Nanomaterial-Incorporated Polysaccharide-Based … 191

1 Introduction

1.1 Drug Delivery

Drug delivery is a process that permits the administration of a medicinal material inside the body, optimizing its efficacy and safety through precise control of factors such as administration rate, timing, location, and route. This procedure entails the release of medicinal substances, administration of the product’s active components, and the subsequent transportation of the therapeutics to the requisite location. It can also be interpretive as a way of providing medication to patients and consequently to improve the concentration of the drug in specific areas of the body over others. To achievethe efficacious drug delivery outcomes, a good therapeutic transport platform is needed. Generally, therapeutic delivery system is employed as a vehicle or carrier for delivering drugs or therapeutic agents. This carrier serves as a link between the patient and the medicine. It might be a medication formulation used for medicinal purposes or a device used to deliver the medicine. This difference between drug and device is significant since it is the condition for drug control agencies’ regulatory supervision of the delivery method [1]. The goal of a medication administration vehicle is to carry the desired amount of medicine to the needed site while avoiding any undesired side effects of the drug on adjacent healthy tissues or cells. Any drug delivery system’s primary objective is to administrate the medicine into the desired area with a safe interaction.
There are so many ways of drug delivery process in which a drug deliveryplatform carries considerable amount of drug in determining the effectiveness of the employed approach. The administration of medication in the form of tablets, capsules, syrups, powder, spray, ointment, etc. is known as conventional drug delivery. It is seen that the dosage is not properly maintained within the therapeutic window while using traditional drug delivery methods since the body eliminates them extremely fast before the complete action of drug. In this process, the drugs metabolize exceed­ingly fast after a single typical dose, causing the drug level to rise and then instantly drop exponentially. During conventional drug delivery approach, the time period could not be sufficient to have a meaningful therapeutic impact, leading to a sub­therapeutic response and variations in plasma drug levels [2]. Although traditional delivery methods are vastly implemented, these methods have several disadvantages, including fast drug administration, quick degradation or metabolism, need of frequent dosage, inadequacy to transport hydrophobic medicines easily, and lack of target selectivity. Numerous pharmaceutical scientists want to produce an advanced thera­peutic administration platform that is less complicated, having effective biodegrad­able and biological compatible properties, environment-sensitive, and selective in its targeting. Any substrate used during the drug delivery process that increases the selectivity, efficacy, and stability of drug administration is referred to as an advanced drug carrier. Therapeutic carriers serve as a means to regulate the release pattern of drugs into the systemic circulation. This modulation can occur through the gradual dispersion of the drug over an extended duration or through the prompt release
192 K. M. Sahu et al.
of the drug specifically at its target, triggered by particular stimuli, such as pH changes, temperature use, and light actuation. Additionally, drug carriers are utilized to improve the pharmacokinetic characteristics, in particular the bioaccessibility, of many medications with subpar water solubility and membrane permeability [3].
Hence, the incorporation of preferred and innovative features in the fabrication of therapeutic delivery carriers is essential to ensure the successful advancement in this field and to make cost-effective products. Nanotechnology has proven to be instru­mental in the advancement of medication delivery platforms, venturing into the realm of drug administration. It achieves this by enabling various components to replicate the complexity and precise structure of biomolecules, thereby expanding its capacity to efficiently transport therapeutic agents. In pursuit of immediate results in this appli­cation, various drug delivery vehicles utilizing nanomaterials have been developed and thoroughly examined [46]. Out of a humongous number of nanoscale-ranged materials, carbon nanomaterials or carbonaceous nanomaterials (CNs) are gaining prominence as prospective materials for fabricating drug delivery systems [7].

1.2 Carbon Nanomaterials

Nanomaterials are generally the materials with unique characteristics and structures at the nanoscale region, with dimensions generally extended across the range from 1 to 100 manometers (nm) [8]. CNs are predominantly composed of carbon atoms and possess distinctive nanoscale properties. These materials offer a wide range of possibilities for medication delivery and various other applications due to their unique properties. Some well-known CNs include carbon nanotube (CNT), graphene and its derivatives, graphene oxide (GO) and reduced graphene oxide (rGO), carbon dots including carbon quantum dot (CQD) and graphene quantum dot (GQD), carbon nanohorn (CNH), carbon nanoonion (CNO), and nanodiamond (ND) [911].
1.2.1 Carbon Nanotube
CNTs are of cylindrical shape and are made up of hexagonally organized carbon atoms. They may be conceived of as rolled up sheets of graphene in a tubular form. According to CNTs’ structural characteristics, there are two main varieties of CNTs: single-walled carbon nanotubes (SWCNTS) and multi-walled carbon nanotubes (MWCNTS). CNTs offer distinct qualities like remarkable strength, and electrical and thermal conductivity, making them of tremendous interest in a sundry kind of scientific and technological disciplines [1216]. In 2005, Dr. Michael Sailor and his co-researchers at the University of California, San Diego, established a technique for l oading anticancer medicines onto SWCNTs and proved the promising effects of SWCNTs for targeted drug delivery towards cancer cells. Since then, SWCNTs have been actively researched in the area of drug administration application because of their capacity to transport medicines, peptides, and other bioactive compounds
Carbon Nanomaterial-Incorporated Polysaccharide-Based … 193
to particular cellular targets, presenting the promise for more effective and specific treatments with less negativeside effects [1720]. On the other hand, MWCNTs were used for medicine administration for the first time in the early 2000s. Researchers started looking at the potential of functionalized MWCNTs as medication admin­istration systems, notably for the curing of cancer [2124]. In order to move and transport medicinal compounds, CNTs have become a new alternative and effec­tive materials. CNT may be modified with biologically active components, namely peptides, proteins, nucleic acids, and medicines and utilized to transport cargo ther­apeutics. Furthermore, CNTs’ huge surface area, which enables a high accommo­dating capacity of therapeutic medicines, is the main advantage in their efficacy in drug delivery applications. Because functionalized CNTs are non-immunogenic and have minimal toxicity, such systems have enormous potential in nanobiotech­nology and nanomedicine [25]. However, the biocompatibility of CNT is influenced by a variety of elements, including, as the manufacturing process, the presence of contaminants (often metallic catalysts), their size and shape, their dispersion and aggregation location, delivery route, and cellular absorption. Therefore, choosing the right material to functionalized CNT should be considered during the production of CNT-based drug delivery carrier [26].
1.2.2 Graphene
A 2D honeycomb lattice is created by arranging a monolayer of carbon atoms to form graphene sheet. Graphene is one of the strongest, lightest, and most conductive substances known to humankind. Scientists Andre Geim and Konstantin Novoselov at the University of Manchester were the first to succeed in isolating and charac­terizing graphene in 2004 [27]. There are two main types of graphene derivatives; one is GO and another one is rGO. GO is a sheet of carbon atoms of monoatomic layer thickness, arranged in a hexagonal lattice, similar to graphene but with several oxygen functional groups bonded to the carbon atoms. These oxygen composed of groups, namely hydroxyl, epoxy, and carboxyl groups, differentiate GO from pure graphene by making it more hydrophilic and chemically reactive. The size and thick­ness of GO sheets might vary depending on the fabrication procedure, although they commonly have horizontal dimensions varying from nanometers to micrometers and a thickness of a few atomic layers [28, 29]. Owing to its distinct features, it is a good option for medication delivery applications. Graphene can carry a consid­erable payload of medications because of its large surface area and ability to form stable connections with drug molecules, permitting regulated release and potentially lowering the frequency of drug delivery. Although properly functionalized graphene may be rendered biocompatible, since its biocompatibility varies depending on its functionalization and size. Surface alterations, such as the incorporation of biocom­patible polymers or chemicals, can improve compatibility with biological systems. To target certain cells or tissues, functionalized graphene materials can be coupled with some targeting ligands, namely antibodies or peptides. As a result, off-target
194 K. M. Sahu et al.
effects are diminished, and medication administration is made more selective. Ther­mally, graphene has good conductivity. It can sometimes be used for cancer therapy based on hyperthermia, where localized heating can be employed to release medi­cations or destroy cancer cells. In MRI and photoacoustic imaging, among other imaging methods, graphene can be utilized as a contrast agent. This makes it easier to monitor how drug-loaded graphene nanocarriers are dispersed throughout the body. Numerous in vitro and in vivo scrutinies have shown well-developed graphene mate­rials with little toxicity. The design of graphene-based medication delivery devices must reduce possible damage, yet safety concerns are crucial. When properly func­tionalized, graphene’s light weight and flexibility allow it to pass through several physiological barriers, including the blood–brain barrier. This characteristic is essen­tial for delivering medications to certain bodily locations. Since drugs that are prone to chemical or enzymatic breakdown require extra care, graphene can be a useful shielding material to protect them from deterioration and increase their durability [3034].
1.2.3 Carbon Nanohorns
A research team from Japan’s Meijo University under the direction of Sumio Iijima made the initial discovery of CNHs in 1999. CNHs are tubular, horn-like nanoscale carbon structures. CNHs resemble the shape of a nanoscale horn because they are constructed of graphene sheets that havebeen curled into conical or horn-like shapes. The shape and size of CNHs can vary, generally relying on the number of walls and the size of horns. One or more layers of graphene sheets make up the horn structure in the common varieties of single-walled carbon nanohorns (SWCNHs) and multi-walled carbon nanohorns (MWCNHs) [3537]. CNHs have a huge surface area and an inte­rior hollow, allowing them to encapsulate a considerable number of drug molecules. This high drug loading capacity is beneficial for delivering therapeutic medicines in concentrated amounts to the target region. Controlled drug release kinetics can be achieved by functionalizing or modifying CNHs. Researchers can create CNH­based drug delivery systems that release pharmaceuticals in a sustained, regulated, or triggered way, boosting therapeutic efficacy and lowering adverse effects by altering surface characteristics or employing stimuli-responsive coatings. CNHs are deemed to be biocompatible in general, making them useful for applications involving medication administration [25, 3842].
1.2.4 Carbon Nanoonions
CNOs are generally used in biological applications such as biological imaging, biological sensing, and environmental remediation and also in electronic application such as capacitors, lithium-ion batteries, fuel cells, terahertz-shielding, and also as catalysis in chemical reaction. Small CNOs can be utilized safely for biological exper­iments since they are not cytotoxic as compared to large CNOs [43]. They make an