Sensors have received a lot of attention in a variety of applications, including health, pharmacy, the environment, and industry . When employing these technical devices, users can chose user-friendly, cost-effective, sensitive, and error-free detecting instruments . The field of biosensors has received a lot of interest over the last years because of their amazing capacity for early disease diagnosis, quick detection of diverse drugs and chemicals, and long-term monitoring . In the recent decade, sensor technology has seen breakthroughs thanks to the usage of nanomaterials with superior physicochemical properties . Nowadays, the development of sensors based on nanomaterials, particularly alginate-based, has raised the interest of many in the biomedical field for monitoring and regulating human health .

Biopolymers are naturally occurring polymeric compounds derived from living organisms . They are mostly used in pharmaceutical and biomedical applications. Biodegradable and bioabsorbable polymers are an excellent choice for a variety of innovative drug delivery systems (DDSs). Biopolymers are also used in cutting-edge scientific applications such as gene expression, tissue engineering, smart drug delivery, and biosensors . Modern medicine and pharmacy are looking for such materials for DDSs because targeted drug delivery is becoming a vital way of carrying drugs. Traditional drug delivery methods including tablets, capsules, syrups, and ointments, have significant disadvantages such as low bioavailability and variability of drug levels in plasma, which makes them incapable of continuous release . In addition, to achieve optimal efficacy and safety, the drug must be administered at a precisely controlled rate and a special target site . To solve these issues in DDSs, biopolymers can be a perfect solution. Because they have several excellent properties that can be crucial in drug delivery, such as low cost, antioxidant and antibacterial activity, non-toxicity, biodegradability, and biocompatibility. Biopolymeric nanoparticles (NPs) can be used in DDSs, and they can protect the drugs from the adverse conditions of the gastrointestinal tract to deliver the active pharmaceutical substance without any damage to its site of action. In addition to that, biopolymers can protect patients from the negative effects of chemicals, serving as a small container to safely store drugs inside. Moreover, biopolymers are not harmful to the human body, as they are antimicrobial, biodegradable, and non-toxic .

Biopolymeric nanoparticles are a very effective material for producing biosensors. In today’s world, people need sensors to monitor various types of pollution. Food contamination with infectious microorganisms or air and water contamination with heavy metals are good examples of the need for sensors . In addition, incurable diseases such as cancer can be detected by biosensors, and the application of biosensors is also very important for medicine and pharmaceuticals . Natural biopolymers are abundant and exhibit variable chemical compositions, customizable characteristics, easy processability, great biocompatibility and biodegradability, and nontoxicity, opening up new avenues for the creation of flexible sensing technologies . Alginate-based nanomaterials are among the most widely studied biopolymers for drug delivery and sensing applications because of their properties.

Figure 2: Applications of alginate-based nanomaterials in sensing and smart drug delivery.

Drug delivery refers to the process of administering therapeutic molecules, such as medications, to patients in a targeted and controlled manner. The main goal is that the drug should be delivered to its intended site of action, at the right time and concentration, and achieve maximum therapeutic efficacy with minimal side effects . This is important because traditional drug delivery methods often result in suboptimal drug concentrations at the target site, leading to inadequate treatment outcomes or unnecessary side effects.

One of the key implications of drug delivery is its potential to enhance the effectiveness and safety of drug therapies. For example, it is possible to deliver medications to cancer cells with little side effects and minimum damage to healthy cells. As a result, DDSs can improve patient compliance and adherence to medications . Furthermore, smart drug delivery can also increase the bioavailability of drugs, which refers to the proportion of the administered drug that enters the target systemic circulation. Another important aspect of drug delivery is its ability to overcome biological barriers and provide the availability in drug-specific body tissues. For example, in the case of Alzheimer’s or Parkinson’s disease, drug delivery methods that can effectively cross the blood–brain barrier are essential for delivering therapeutic agents to the brain . Nanotechnology has emerged as a promising tool in smart delivery systems. Nanoparticles can be designed to pass through biological barriers and reach specific sites in the body, increasing the delivery efficiency of drugs .

In addition to drug delivery, sensing technologies are also of great importance in healthcare. Sensing technologies enable healthcare professionals to monitor patients’ health conditions, track the effectiveness of treatments, and detect any potential risks or complications . Recently, researchers and medical organizations have begun using low-cost biosensors to monitor food and water toxins, human biological processes, accurate health diagnostics, and for other applications . Biosensor-based technologies are essential to assess samples precisely in modern medical equipment . Biosensors are now transitioning from laboratory-based systems to distributed health care. Traditional scientific diagnosis involves taking a sample from the patient and sending it to an analytical laboratory. In these point-of-care tests, the patient has to wait several hours for results. The development of compact and portable miniaturized sensors has enabled the detection of different biomarkers for continuous, real-time human health monitoring . Temperature, heart rate, electrical conductivity, dehydration, and glucose are some of the indicators that sensors can analyze.

Traditional methods of drug administration only deliver non-targeted drugs to the human body without any protection. As a result, the chemical substance can have a negative effect not only on the site of drug action but also on other parts of the human body. Despite several advantages, such as simplicity of administration and patient acceptance, conventional DDSs have significant limitations and disadvantages. They have limited efficacy through varying absorption rates of the drugs when given orally. Also, a low-pH environment and digestive enzymes in the gastrointestinal tract can break down some medications before they reach the bloodstream . In addition to this, lack of selectivity can minimize their effectiveness. Also, drug absorption may be high in detoxifying organs such as liver and kidneys, causing toxicity in those organs . Another drawback is that current drug delivery technologies yield only limited bioavailability and change drug levels in plasma, making them incapable of long-term release. Without proper dispensing techniques, the entire treatment process may fail. In addition, the drug must be delivered at a precisely regulated rate and location to ensure optimal efficacy and safety . Medicines can become the cause of disease when considering the disadvantages such as instability, uncontrollable discharge, irritation and pain, poor absorption, and enzymatic degeneration. However, if nanoparticles, especially biopolymer nanoparticles, are applied to drug delivery methods, the aforementioned drawbacks faced by traditional drug delivery today can be overcome.

Drug delivery via nanoparticles has transformed the world of medicine in recent decades. These techniques aim to improve disease treatment by increasing targeted accumulation of drugs into diseased tissues while minimizing side effects and toxicity. Nanoparticle-based drug delivery strategies have evolved since the 1970s, when researchers first investigated the use of nanoparticles as drug carriers. Since then, tremendous progress has been achieved in the design, manufacture, and characterization of nanoparticle-based DDSs. The use of alginate in drug delivery goes back to the 1980s, when researchers first investigated its ability to encapsulate pharmaceuticals. Over time, researchers have improved the formulation procedures for alginate-based nanoparticles to improve drug-loading capacity, stability, and controlled release characteristics. To improve the formulation of alginate nanoparticles, several methods have been developed, including emulsion-based approaches, solvent evaporation, and nanoprecipitation. Advances in alginate-based nanoparticle design have resulted in increased drug encapsulation efficiency, allowing for larger drug payloads within the nanoparticles. Biopolymeric nanoparticles have become the most commonly used nanoparticle DDSs in recent years.

Nanoparticle systems offer several advantages in drug delivery . One of the major advantages of nanoparticle-based DDSs is that they can protect drugs and ensure the delivery of drugs to targeted cells or tissue . By encapsulating drugs within nanoparticles, the delivery system can specifically target the diseased tissue, ensuring that the highest concentration of the drug reaches the desired location while minimizing systemic exposure. This targeted delivery leads to enhanced therapeutic outcomes and reduced side effects . Another advantage of biopolymeric nanoparticles in drug delivery is the ability to improve oral bioavailability. Nanoparticles made from biopolymers can enhance the absorption rate and stability of orally administered drugs, allowing for improved treatment efficacy of medicines . Furthermore, biopolymeric nanoparticles can sustain the medicine or gene effect in targeted tissues. This sustained release of medication extends the duration of the effect of the drug, ensuring optimal treatment efficacy. Additionally, biopolymeric nanoparticles can carry various functional groups on their surface enabling targeted drug delivery. These functional groups can include ligands or antibodies that specifically bind to the target cells or tissues . Stimuli-responsive nanoparticles help reduce toxicity and control drug biodistribution .

The preparation of alginate-based nanoparticles involves a series of steps that utilize green chemistry principles . Green chemistry involves using sustainable and environmentally friendly processes to minimize the use of hazardous materials and reduce waste. To begin the preparation of alginate-based nanoparticles, a nontoxic metal ion is chosen as the precursor. This precursor can be combined with alginate, a natural polymer derived from seaweed, in a purified natural solvent such as water. Then, a reducing agent is selected to reduce the metal ions and form nanoparticles. One environmentally friendly option for reducing the metal ions and forming nanoparticles is to use sodium alginate as both a capping and reducing agent . The synthesis of alginate-based nanoparticles involves the following steps: First, alginate polymer is dissolved in water. Next, the metal salt is added to the alginate solution, and the nanoparticle formation reaction is initiated by adjusting the pH. During the reaction, sodium alginate acts as a reducing agent, as it contains carboxylic groups that can interact with the divalent cations and reduce them to form nanoparticles. After the formation of metal nuclei, these nuclei grow and accumulate within the alginate matrix, resulting in the formation of alginate-based nanoparticles. The morphology and size of the nanoparticles can be controlled by adjusting various specifications of materials such as the concentration of alginate, metal ion precursor, pH, and reaction time. When it comes to the alginate–polymer combination, there are various methods available for the preparation of alginate-based biopolymeric nanoparticles, each with its advantages and limitations. One common method is the ionotropic gelation method, which involves the cross-linking of alginate and polymer in the presence of divalent ions such as calcium or zinc. The microemulsion protocol is another technique that can be used to prepare alginate nanoparticles. The hydrogel formation method is yet another method for preparing alginate–polymer nanoparticles . Another method for preparing alginate–polymer nanoparticles involves the use of oil-in-water emulsions in polymer and calcium alginate solutions to prepare polymer NPs and calcium alginate NPs separately .

Characterization techniques play a crucial role in analyzing biopolymeric nanoparticles, providing valuable information about their physical and chemical properties. These techniques allow researchers to understand the structure, stability, surface properties, and drug release behavior of biopolymeric nanoparticles, enabling them to optimize drug delivery strategies and ensure efficacy and safety . The most crucial characteristics of nanoparticles are particle size, morphology, zeta potential, and surface area.

Morphology of nanoparticles: There are many tools available for determining the morphology of nanomaterials. However, the most commonly used methods are scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The shape and size of the nanoparticles can be determined by these two methods . TEM is extensively utilized and can differentiate between nanocapsules and nanospheres, as well as measure the thickness of the nanocapsule wall . Another important morphological feature of polymers is the surface of the polymers, and atomic force microscopy (AFM) can be utilized to detect surface features of polymeric nanoparticles. It is very useful tool that offers high-resolution images in three dimensions at the nanometer scale .

Nanoparticle size: The nanoparticle size can be determined using a variety of methods including dynamic (DLS) and static (SLS) light scattering; TEM, SEM, and AFM are also widely employed . DLS and SLS can detect particle size by determining changes in distribution of particle size, while TEM and SEM yield images of separated particles .

Surface area: The reactivity of nanoparticles and their ability to interact with ligands highly depend on their surface area. This property of the nanoparticles can be detected directly by adsorbing an inert gas under various pressures to form a monolayer of gas coverage. The surface area of nanomaterials can also be determined by X-ray photoelectron spectroscopy and secondary ion mass spectroscopy .

Zeta potential: The zeta potential of nanoparticles can be calculated from the electrophoretic mobility of particles in a particular solvent using the Doppler approach, which measures particle velocity as a function of voltage. The determination of the zeta potential is crucial in understanding the mechanism of drug–nanoparticle interactions .

In addition to the methods described above, Fourier-transform infrared spectroscopy is frequently used to determine the chemical composition and functional groups of biopolymeric nanoparticles .

The use of biopolymeric nanoparticles, specifically chitosan–alginate nanoparticles, offers several advantages in different fields such as agriculture, medicine, food packaging, and DDSs . One of the advantages of using alginate-based nanoparticles is their biocompatibility. These nanoparticles are made from nontoxic and biodegradable polymers, making them safe to use in various applications . Another advantage is their low cost, as alginate and other polymers are readily available and affordable materials. The combination of alginate and other polymers in nanoparticles results in increased cross-linkage, leading to a denser structure . This denser structure enhances the stability and durability of the nanoparticles, making them suitable for long-term use. Moreover, the alginate-based nanoparticles have demonstrated their suitability for the controlled release of bioactive materials. The nanoparticles can encapsulate and deliver various active compounds, such as polyphenolic compounds, in a controlled manner. Also, these combined nanoparticles have demonstrated enormous advantages for sensing applications. First, alginate-based nanoparticles have a high surface area-to-volume ratio. This feature allows for increased interaction with the target analyte, leading to enhanced sensitivity and detection capabilities. Additionally, alginate-based nanoparticles have excellent biocompatibility, which is crucial for sensing applications in biological systems . Their biocompatible nature ensures minimal interference with the sample or surrounding environment, thereby enabling accurate and reliable measurements. Moreover, alginate-based nanoparticles offer excellent stability and durability, which is essential for long-term sensing applications . Furthermore, these nanoparticles can encapsulate and protect sensitive sensing elements, such as enzymes or receptors, enhancing their stability and preserving their activity over extended periods. Also, alginate-based nanoparticles possess excellent mechanical and electrical properties, overcoming the limitations typically associated with biomaterials in sensing applications .

Drug delivery systems are one of the areas in which many scientists are working today. One of the leading areas of research is the search for new DDSs and new modes of administration. It includes multidisciplinary scientific approaches to achieve significant progress in increasing the therapeutic index and bioavailability of certain drugs . Conventional drug delivery techniques may be ineffective in many applications. Furthermore, it is difficult to manage the components that are produced in an acidic or basic environments, resulting in a reduction in the therapeutic impact of the medications.

Table 1: Alginate-based nanoparticles and their characteristics for drug delivery.

Boronated chitosan/alginate nanoparticles (BCHI/ALG NPs) were developed and evaluated as a targeted mucoadhesive DDSs for cervical cancer . The BCHI/ALG NPs were less than 390 nm in size and showed a drug encapsulation efficiency of 98.1–99.8%, and a drug loading capacity of 326.9–332.7 g/mg. Surprisingly, boronated chitosan-loaded alginate demonstrated a greater mucoadhesive capacity compared to CHI/ALG NPs, yielding sustained release of the medicine and promising results as a transmucosal DDSs for hydrophobic medicines.

Another enhanced cancer drug delivery system was developed by Iranian scientists. They conceived a nanoparticles-in-nanofibers DDS, which they called nano-in-nano delivery technique, to mitigate limitations of simple nanostructures such as low stability and unsuitable drug release features. They investigated capsaicin-loaded alginate nanoparticles embedded in polycaprolactone–chitosan nanofiber mats. This DDS can extend the release time of capsaicin to more than 500 h compared to the initial 120 h. Furthermore, in vitro tests showed the effective inhibition of MCF-7 human breast cells without any damage to human dermal fibroblasts (HDFs). The created new alginate-based nanoplatform can be used in targeted and prolonged drug delivery of capsaicin in cancer prevention and therapy .

Alginate-based fully natural nanoparticles were developed and used for cancer treatment. Pakistani scientists investigated amygdalin in an alginate–chitosan-based matrix . Amygdalin is a natural material and it has very strong anticancerous activity. Scientists achieved over 90% drug encapsulation of amygdalin and sustained drug release for 10 h. The results also showed increased cytotoxicity and controlled release of the drug because of the biodegradable and biocompatible carrier. Alginate–chitosan nanoparticles can be employed as an effective drug delivery vehicle for sustained and controlled amygdalin release, with an increased cytotoxic effect on cancerous cells while sparing normal cells and tissues.

Alginate nanoparticles can be applied to ocular DDSs . Kianersi and coworkers investigated alginate-based nanoparticles for betamethasone sodium phosphate delivery in the human eye . According to the literature, less than 5% of the conventional medication reaches the targeted eye tissue. This emphasizes the need to invent a DDS that stays on the surface of the eye and ensures continuous drug release, increasing the bioavailability of the medication and reducing the need for frequent drug administration. Scientists prepared alginate nanoparticles coated with the two biopolymers chitosan and gelatin. The results demonstrated better encapsulation efficacy (40%) and loading capacity (7%). In addition, in vitro drug release experiments indicated a sustained drug release over 120 h. The longer release time improves patient compliance by reducing administration frequency. Furthermore, continuous drug release can aid in keeping the medication concentration within its therapeutic range. These first findings indicate that the produced alginate nanoparticle-based delivery method has promising potential.

Sodium alginate has many carboxylate groups and can be used as a reactive polymer. In the preparation of chemically modified alginate nanoparticles, the dehydration condensation reaction between carboxylate (–COO–) and other chemical groups, such as amino groups, plays a crucial role in forming the cross-links that stabilize the nanoparticles. The procedure generally includes preparing an alginate polymer solution to which a compound with amino groups is subsequently added. In the presence of a cross-linking agent or under appropriate conditions, the carboxylate groups of alginate and the amino groups of the other compound undergo dehydration condensation processes. These cross-links aid in stabilizing the alginate nanoparticles while also controlling their size, shape, and characteristics. These alginate nanoparticles have potential in drug delivery, food technology, and other disciplines that need regulated and focused distribution.

Fenn et al. introduced a methacrylate alginate matrix in which carboxyl groups of alginate were cross-linked with methacrylate and dialdehyde. They used this matrix as a sealant patch for the lungs and for the controlled delivery of soluble drugs such as DOX. The oxidation of alginate produces functional aldehyde groups, which that can form imine bonds with proteins prevalent in many tissues. The controlled release and bioavailability of DOX encapsulated in the alginate matrix enabled the creation of drug-eluting adhesive patches, which were successful in reducing human lung cancer cell (A549) survival .

Another research studied modified alginate materials for mucoadhesive drug delivery. Scientists combined the alginate hydroxy groups with maleimid-terminated PEG. This novel mucoadhesive biopolymer exhibited polymer–mucus glycoprotein interactions. The results showed that the new alginate-based mucoadhesive matrix can enhance the prolonged release of drugs as well as the cytotoxicity properties of drugs .

Similar research was conducted with starch and alginate for drug delivery applications . Researchers modified the alginate backbone with starch by a green facile technique for controlled drug delivery applications. The authors used theophylline and bovine serum albumin as drug models and alginate–starch polymer as a drug matrix for studying the controlled release. Research confirmed that modification of alginate with starch can improve the encapsulation efficiency of the matrix from 60% to 75%. Moreover, this novel drug carrier protected drugs from the gastric environment and provided the complete release of model drugs in intestinal fluid. In addition, the prepared matrix has zero toxicity and high biocompatibility.

Alginate nanoparticles have become known as a promising tool for sensing applications in recent years . With their large surface area, alginate nanoparticles provide space for the immobilization of sensing elements, allowing for enhanced sensitivity and selectivity . Additionally, alginate nanoparticles possess excellent stability and biocompatibility, ensuring that they are eligible for multiple sensing applications without compromising the integrity of the system. Furthermore, alginate is a natural polymer, making it a favorable choice for sensing applications because of its biocompatibility and low toxicity . The application of alginate nanoparticles in sensing is diverse, with notable applications in clinical diagnostics, environmental monitoring, food quality control and processing, pharmaceuticals, and agriculture. One area where alginate nanoparticles have shown significant potential is in the field of clinical diagnostics. Researchers have successfully utilized alginate nanoparticles for the detection and quantification of various analytes, such as proteins, enzymes, nucleic acids, and pathogens. For example, alginate nanoparticles have been used for the detection of cancer biomarkers in body fluids, allowing for early diagnosis and improved treatment outcomes . In environmental monitoring, alginate nanoparticles have been employed for the detection of pollutants and contaminants in water and air, helping to ensure environmental safety . The main factor for the sensing ability of alginate is the surface charge on the polymer. It is critical in enabling quick electron transfer between an enzyme and an electrode surface, triggering the enzyme’s catalytic function for rapid biosensing .

One key advantage of using nanosensors in environmental sensing is their ability to detect a wide range of contaminants with high selectivity, accuracy, and sensitivity . One of the main advantages of alginate-based nanoparticles is their biocompatibility and biodegradability, which make them ideal for use in environmental sensing. Furthermore, the availability of alginate from marine sources adds to its appeal as a sustainable and renewable material for nanoparticle synthesis . These nanoparticles have demonstrated potential in sensing applications, including temperature, humidity, water level, and various environmental pollutants.

Heavy metal and volatile organic compounds sensing: Metal sensing has become a crucial area of research because of the detrimental effects of heavy metal ions on living organisms and ecosystems . Metal ions, such as silver, are commonly found in water systems because of industrial activities. In recent years, the use of nanoparticles for metal sensing has gained significant interest among researchers and scientists . Nanoparticles offer several advantages for metal sensing, including high sensitivity, real-time detection, and ease of sample processing . Alginate-based nanoparticles have emerged as a promising platform for metal sensing. First, alginate is non-toxic and biocompatible, making it safe for use in various applications . Second, alginate has carboxyl groups, which can capture metallic cations in solutions and achieve local enrichment of the metal ions inside the nanoparticles . This property allows the alginate-based nanoparticles to effectively bind and detect heavy metal ions present in water systems. The synthesis of alginate-based nanoparticles for metal sensing involves the incorporation of metallic nanoparticles, such as silver nanoparticles or zinc oxide nanoparticles, into the alginate polymer network. This can be achieved through various methods, including reduction reactions, electrochemical deposition, or deposition-precipitation. The resulting hybrid nanomaterials exhibit synergistic properties of both the inorganic nanoparticles and the alginate polymer, leading to superior functionality and enhanced metal sensing capabilities .