1. INTRODUCTION:

Nanos means Extremely Small or Dwarf. Nanoparticles are solid particles or particulate dispersions that range in size from 10 to 100nm. The drug is dissolved, entrapped, encapsulated, or bound using a nanoparticle matrix. Nanocapsules are systems in which the medicine is contained within a hollow surrounded by a unique polymer membrane, in contrast to nanospheres, which are matrix systems in which the medication is uniformly and physically distributed. The particles that fall between 1 to 1000nm in size are referred to as "nanoparticles" (NPs). Depending on the preparation method, one can acquire nanoparticles, nanospheres, or nanocapsules. Biodegradable polymeric nanoparticles, also referred to as long-circulating particles, coated with hydrophilic polymers such as poly (ethylene glycol) (PEG), have been utilized as possible drug delivery vehicles in recent years due to their capacity to target a particular organ and circulate for a prolonged period of time^1-4. The primary goals of creating nanoparticles as a delivery system are to regulate their size, surface properties, and the release of pharmacologically active substances. Because of their small size and large surface area, nanoparticles—which can range in size from 1 to 100 nanometers (nm)—have unique physical and chemical properties. The characteristics of nanoparticles are greatly influenced by their size, shape, surface characteristics, and the material they are made of. Because of their special characteristics, nanoparticles can interact with biological systems in ways that larger molecules or particles cannot. Nanoparticles of some materials exhibit superior adsorptive and catalytic properties. This enables the drug's site-specific effect to be achieved at the optimal therapeutic rate and dosing schedule^5-6. Nanomaterials are sometimes known as "zero-dimensional" NPs. All of their aspects serve as the foundation for this definition. Metals, polymers, lipids, ceramics, and natural materials such as proteins and sugars may all be used to create nanoparticles. The nanoparticles' specific characteristics and functionalities are determined by the materials used and the technique of synthesis. Gold nanoparticles, for example, are extremely stable and biocompatible, whereas polymeric nanoparticles may be created to deliver drugs in a regulated manner. A group of nanoparticles is referred to as "nanoparticulate matter," highlighting the collective behaviour of these particles. They are separated into numerous categories based on their traits, dimensions, and shapes⁷.

Fig:1. Nanoparticles

Nanoparticles have received a lot of interest in medication delivery because they can enhance the pharmacokinetics and pharmacodynamics of medicinal medicines. Traditional drug delivery systems frequently have challenges with poor solubility, limited bioavailability, and off-target adverse effects. Their unique physical and chemical properties, including as a greater surface area-to-volume ratio and the ability to encapsulate a variety of medicinal compounds, make them particularly helpful in drug delivery systems⁸.

1.1. Delivery of Nanoparticles for Drug:

Options for extended drug release, enhanced transport across biological barriers, and precise targeting of cancerous tissues or cells are offered by Nano-based methods^9-10. One can regulate the nanomaterials' activity and administer a range of anticancer medications by carefully regulating their size, shape, and chemical makeup (morphology). Organic, inorganic, lipid, and protein molecules have been used to make a wide variety of nanomaterials, which are typically between 1 and 1000nm in size¹¹. More effective therapeutic effects are possible when poorly soluble medications are made more soluble and bioavailable by nanoparticles. By targeting particular cells or tissues, they can be tailored to enhance drug release, lessen side effects, and increase therapeutic efficiency. Numerous therapeutic substances, such as small molecules, proteins, and nucleic acids, are transported by liposomes, dendrimers, and polymeric nanoparticles. This sophisticated drug delivery method has the potential to significantly improve treatment results in cancer, gene therapy, and chronic illnesses. They can improve a drug's ability to go to specific parts of the body, minimizing side effects and increasing therapeutic effectiveness. Because it may reduce damage to healthy cells by customized delivery, this is particularly beneficial for treating conditions like cancer ^12-13. Nanoparticles in medication delivery are tiny carriers ranging in size from 1 to 100 nanometers that are intended to transfer therapeutic drugs more efficiently to particular areas in the body. Nanoparticles can improve therapeutic solubility, stability, and bioavailability, especially for drugs that are weakly water soluble, because of their small size, huge surface area, and ability to be tailored for certain properties. Depending on the drug's physicochemical properties, the drug may be physically trapped in the hydrophobic cores of micelles, similarly confined in the aqueous space, or intercalated into the lipid bilayer of liposomes. The target drug dissolves, becomes stuck, adheres, or is enclosed within a polymeric matrix in nanospheres. There is a chance that antigen-loaded nanospheres will be applied to vaccination administration. Drugs can be delivered via the BBB using NPs^14-17.

2. Types of Nanoparticles:

· Two primary types of nanoparticles exist:

Fig:2. Nanoparticle Types

· Nanoshpere - Drugs are incorporated in the matrix or adsorbed onto the surface of solid core spherical particles called nanospheres. (Kind of matrix)

· Nanocapsule - A medication is essentially encased within a nanocapsule, which is a system with a polymeric sheath surrounding the core. (Type of reservoir)

2.1. Polymer-Based Nanoparticles or Polymeric Nanoparticles:

Fig:3. Polymeric Nanoparticle

These nanoparticles are biocompatible and biodegradable; medications that have been encapsulated can be released gradually. They may be efficient carriers of both hydrophilic and hydrophobic medications.

· Applications: Drug delivery systems, gene therapy, and vaccine formulations.

· Examples: PEG, or polyethylene glycol, Chitosan, PLGA, or Polylactic-co-glycolic acid¹⁸.

2.2. Nanoparticles Based on Lipids:

Fig: 4. Nanoparticle Based on Lipids

These biocompatible nanoparticles, which are predominantly made up of lipids, may encapsulate both hydrophilic and lipophilic medicines, improving medication stability and bioavailability.

· Application: Utilized in vaccine formulations and drug delivery systems, particularly for medications that are poorly soluble.

· Examples: Liposomes, nanostructured lipid carriers (NLCs), and solid lipid nanoparticles (SLNs)¹⁹.

2.3. Carbon-Based Nanoparticles:

These materials have outstanding electrical, mechanical, and thermal characteristics. Their vast surface area promotes cellular contact and efficient medication delivery.

· Application: Used as scaffolds in tissue engineering, drug delivery, and biosensing.

· Examples: Fullerenes, Carbon nanotubes (CNTs), Graphene²⁰.

2.4. Metallic Nanoparticles:

Metallic nanoparticles are recognized for their distinct optical, electrical, and catalytic capabilities. For example, the surface plasmon resonance of gold nanoparticles makes them useful for targeted therapy and imaging.

· Application: These nanoparticles find extensive use as antibacterial agents, photothermal treatment, medication delivery, and diagnostics.

· Example: Iron (Fe), platinum (Pt), silver (Ag), and gold (Au)²¹.

2.5. Ceramic Nanoparticles:

Ceramics are robust and have large surface areas, making them useful for a variety of applications. Silica nanoparticles, in particular, may be easily tailored for specialized applications.

· Application: utilized as medicinal chemical carriers, imaging agents, and targeted drug delivery.

· Examples: Silica (SiO₂), Titanium dioxide (TiO₂), Hydroxyapatite (HA)²².

3. METHODS OF PREPARATION:

3.1. Single and double emulsion techniques:

Emulsion methods, notably single and double emulsions, are frequently utilized in nanoparticle synthesis due to their capacity to encapsulate diverse materials, manage particle size, and improve end product stability. Single emulsion procedures include dissolving a medication or active ingredient in a continuous phase (typically an organic solvent) and then emulsifying it in an aqueous phase to create nanoparticles. Hydrophilic molecules are encapsulated in an oil phase and then dispersed in a continuous aqueous phase using double emulsions (W/O/W or water/oil/water). This is especially handy with complicated formulas^23-24.

3.2. Solvent Evaporation:

Fig: 5. Nanoparticle preparation using the solvent evaporation method

A common technique for creating nanoparticles, particularly for drug delivery purposes, is solvent evaporation. A polymer or medication is dissolved in a volatile organic solvent, which subsequently evaporates to produce nanoparticles, according to the solvent evaporation method. This method is useful for encapsulating hydrophobic medicines, resulting in controlled release and improved stability. To create a homogenous solution, a suitable polymer (PLGA, PCL, etc.) or medication is dissolved in a volatile organic solvent, like dichloromethane (DCM) or chloroform. Usually water-in-oil (W/O) emulsion, a stable emulsion is produced via ultrasonication or high-speed stirring^25-26.

3.3. Polymerization Method:

Fig:6. Preparation of Nanoparticle by Polymerization Method

Emulsion polymerization and dispersion polymerization are its two types. This method produces nanoparticles in an aqueous solution by polymerizing monomers. After polymerization is finished, drugs are added either by adsorption onto nanoparticles or by dissolving in the polymerization solvent. Before being resuspended in an isotonic surfactant-free medium, the nanoparticle solution is first purified by ultracentrifugation to eliminate the various stabilizers and surfactants utilized in polymerization. Polybutylcyanoacrylate (alkylcyanoacrylate) or poly nanoparticles have been reported to be produced using this technique. The concentration of the stabilizers and surfactants used determines the size of the particles and the creation of nanocapsules^27-29.

3.4. Salting-out Method:

The concentration of the stabilizers and surfactants used determines the size of the particles and the creation of nanocapsules. Salting out is the process of precipitating nanoparticles from a solution using a salt that lowers the polymer or drug's solubility. This approach is particularly useful for producing nanoparticles of regulated sizes and compositions. When salt is introduced to a solution, it dissociates into individual ions. These ions interact with water molecules, limiting the amount of water available to dissolve the polymer or medication. As additional salt is added, the solute's solubility decreases, leading it to precipitate out of solution. The precipitated particles can combine to form nanoparticles, which are stabilized by surfactants or other substances introduced during the process.^30-31

3.5. Emulsification Diffusion:

The emulsification diffusion method is a technique for producing nanoparticles, notably those for medication administration. This technology combines emulsification and diffusion processes to produce nanoparticles with certain sizes and characteristics. In the emulsification diffusion process, an organic phase containing a polymer or medication is emulsified in aqueous solution. The method involves letting the organic solvent permeate the aqueous phase, which causes nanoparticles to precipitate. A polymer (like PCL or PLGA) or drug is dissolved using a volatile organic solvent (like ethanol or acetone). An aqueous phase, usually containing surfactants (such polyvinyl alcohol), is combined with the organic phase. To create a stable emulsion, this mixture is stirred or sonicated at high speeds. The drop in solubility causes the polymer or medicine to precipitate and create nanoparticles. The process may be manipulated by changing factors like stirring speed and temperature^32-33.

4. Current Status of Nanoparticles:

Since nanoparticles can improve the solubility, stability, and bioavailability of medicinal drugs, they are becoming more and more acknowledged as an essential feature of drug delivery systems.

· Targeted Delivery: The functionalization of nanoparticles with ligands that target specific cells or tissues is made possible by advancements in surface modification techniques. This method reduces off-target effects while increasing treatment effectiveness ³⁴.

· Combination Therapies: Nanoparticles are employed to deliver numerous therapeutic compounds at the same time, resulting in synergistic benefits in treatments such as cancer therapy. Tumor resistance mechanisms can be overcome by this multi-drug delivery strategy³⁵.

Numerous NPs have been created and assessed in preclinical and clinical research. For drug delivery, imaging, treatment, and theragnostic uses, polymeric nanoparticles hold great potential. Early research on a number of novel nanoparticles suggests that they could improve and streamline cancer detection and therapy. Over the past ten years, polymeric nanoparticles—such as biodegradable NPs, micelles, and stimuli-responsive NPs—have gained popularity due to their unique physical characteristics, which include enhanced circulation time in the body, controlled release, and protection of deliverable agents. Stimuli-responsive polymeric NPs have more potent anticancer effects because of their highly regulated release patterns both in vitro and in vivo. Researchers can use NP kinetics to track tumor activity since polymeric nanoparticles (NPs) enhance contrast in practically all medical imaging modalities. Current research focuses on enhancing targeted delivery, which employs nanoparticles to route medications to particular illness locations while limiting harm to healthy tissues. Despite their potential, there are still issues with scalability, toxicity, and long-term safety, notably in terms of nanoparticle accumulation in organs and immune responses. The regulatory procedure is very complicated, including extensive safety and efficacy assessments. However, advances in stimuli-responsive nanoparticles and customized medicine are opening the way for more targeted and effective therapies. NPS can also be utilized for MI diagnostics. Overall, nanoparticles are transforming medication delivery, particularly in cancer, gene therapy, and chronic illnesses; nevertheless, more research is needed to remove current hurdles and enhance their clinical application. By giving the NPs a physical source, such as NIR lasers, external heat, or lighting photosensitive components, a burst release of medication can be generated if tumors have a high concentration of NPs^36-38.

5. CHALLENGES:

· Manufacturing and Scale-Up: Nanoparticle manufacturing is challenging due to its complexity and high expense, especially when scaling up to clinical and commercial volumes.

· Manufacturing Consistency: Maintaining constant size, shape, and surface properties throughout nanoparticle synthesis is critical for medicinal effectiveness and safety³⁹.

· Biological Barriers: Effective drug delivery requires addressing difficulties such as cellular absorption, blood-brain barrier penetration, and immune system clearance⁴⁰.

· Stability and Controlled Release: To achieve consistent treatment effects, current hurdles include maintaining nanoparticle stability and obtaining precise control over drug release kinetics. Nanoparticles may aggregate or degrade over time, compromising their stability and efficacy during storage and transportation⁴¹.

· Selective Targeting: One of the main benefits of employing nanoparticles in drug delivery systems is selective targeting; nevertheless, in order to accomplish successful targeting, a number of issues must be resolved⁴².

· Receptor Binding: Target cells frequently express a multitude of receptors, and their amounts might vary between people and tumor populations. The geographical distribution and accessibility of target receptors might differ greatly, influencing nanoparticle binding effectiveness⁴³.

· Formulation Stability: Nanoparticles have a tendency to aggregate or degrade over time, which affects their stability and effectiveness.

· Release Profile: It might be challenging to achieve regulated and prolonged medication release from nanoparticles. Burst release or incomplete release can impact therapeutic efficacy. Designing nanoparticles that release their payload at the appropriate time and location within the body can be difficult⁴⁴.

· Storage Issues: For the storage, transport and maintaining stability of nanoparticles requiring specific conditions. Nanoparticles may aggregate or degrade over time, compromising their stability and efficacy during storage and transportation⁴⁵.

Fig:7. Various Challenges of Nanoparticles in drug delivery

Nanomaterials physicochemical qualities have a substantial impact on their biocompatibility and toxicity in biological systems^46-47. Regulatory hurdles further complicate the development process, as the evolving landscape for nanomedicine creates uncertainty in approval pathways. Finally, challenges in manufacturing and scalability can limit the widespread application of these technologies. To fully utilize drug delivery systems based on nanoparticles, these problems must be resolved. Because of possible issues with nanoparticles that might not be immediately apparent, drug distribution presents a challenge to guaranteeing the safety of human health. Because of their adverse interactions with biological entities, nanocarriers may be hazardous when used in cancer therapy⁴⁸. In drug delivery systems, nanoparticles present a number of challenges that need to be overcome before they may be applied successfully in clinical settings. First and foremost, as some nanoparticles may have harmful effects on biological systems, their possible toxicity and biocompatibility may present significant safety concerns⁴⁹. Second, concerns with stability and storage might cause aggregation or deterioration, reducing their therapeutic effectiveness⁵⁰. Furthermore, selective targeting remains tricky, as nanoparticles may attach non-specifically to healthy cells, reducing their intended effect⁵¹.

6. Future Prospective:

· Focused Delivery: By specifically targeting cancer cells or other diseased tissues, nanoparticles can significantly improve therapy efficacy while reducing side effects. By delivering drugs straight to particular cells or tissues, nanoparticles might decrease side effects and improve therapeutic efficacy.

· Combination Therapies: Nanoparticles can enable the co-delivery of numerous medications or therapeutic agents, increasing the efficacy of combination therapy for complicated illnesses such as cancer.

· Reduced Immunogenicity: Improved biocompatibility and decreased immunogenicity of nanoparticles may lead to medications with fewer side effects, increasing patient compliance and quality of life.

· Gene and RNA Delivery: Nanoparticles are likely to play an important role in transporting genetic material for gene therapy, offering up new possibilities for treating genetic abnormalities and illnesses.

· Regenerative Medicine: Nanoparticles can be used in regenerative medicine to transfer growth factors or stem cells, which aid in tissue regeneration and repair.

· Cross Biological Barriers: The ability of nanoparticles to cross difficult biological barriers, such the blood-brain barrier, has shown promise in the treatment of neurological disorders.

Fig:8. Future Prospective

Nanoparticles' capacity to cross biological barriers, such the blood-brain barrier, opens up new therapeutic options for neurological conditions. As research progresses, prioritizing safety and regulatory issues will be critical for incorporating new technologies into clinical practice. All things considered, nanoparticles could significantly increase the effectiveness of medication delivery systems, paving the way for innovative therapeutic strategies. The use of nanoparticles in drug delivery systems has enormous potential to revolutionize therapeutic approaches in the future. Targeted delivery made possible by nanoparticles can concentrate drugs in particular locations, particularly in cancer treatment, reducing side effects and boosting efficacy⁵². Furthermore, nanoparticles can provide regulated and sustained release, improving patient compliance by reducing dose frequency. Advances in customized medicine may enable the customization of nanoparticles based on unique patient profiles, enhancing therapeutic results⁵³. The future of nanoparticles in drug delivery systems promises dramatic advances that might greatly improve therapeutic effectiveness and patient outcomes. Nanoparticles allow drugs to be precisely targeted to certain tissues, reducing systemic side effects and increasing therapeutic advantages, particularly in cancer ⁵⁴. For therapeutic formulations to overcome current limitations, their ability to improve the solubility and bioavailability of poorly soluble medications is essential ⁵⁵. Nanoparticles can provide regulated release mechanisms, delivering prolonged therapeutic doses and enhancing patient compliance⁵⁶. Advances in biocompatibility and safety evaluations will pave the road for regulatory approvals and clinical applications, accelerating the use of nanoparticle-based therapeutics in personalized medicine. All things considered, adding nanoparticles to medication delivery systems could revolutionize the treatment of a variety of illnesses. t is anticipated that emerging technologies, like multifunctional nanoparticles, may make it possible to provide medications and diagnostic agents simultaneously, allowing for real-time therapy response monitoring⁵⁷.

Applications:

1) Passive Targeting: Nanoparticles can accumulate more in tumor tissues than in normal tissues because of their size, which allows them to take advantage of the increased permeability and retention (EPR) effect.

2) Co-Delivery Systems: Nanoparticles can carry multiple drugs simultaneously, allowing for combination therapies that enhance therapeutic efficacy and overcome drug resistance.

3) Gene Therapy: Nanoparticles can deliver nucleic acids (DNA, RNA) for gene therapy, providing a method to target genetic diseases. Lipid-based nanoparticles (like liposomes) and polymeric nanoparticles are commonly used for this purpose.

4) Vaccine Delivery: Nanoparticles can enhance the delivery of vaccines by acting as adjuvants or carriers, improving immune response and stability of the vaccine.

5) Managed Discharge: Drugs can be released gradually and under control thanks to nanoparticles.

6) Targeted Distribution: Drug efficacy can be increased and negative effects can be minimized by engineering nanoparticles to target particular cells or tissues.

7. CONCLUSION:

In conclusion, nanoparticles offer a transformative approach to medication delivery, enabling enhanced targeting, improved bioavailability, and the potential for personalized therapies. To reach their full potential in clinical settings, a number of issues still need to be resolved. Issues related to toxicity, biocompatibility, and the stability of nanoparticle formulations pose significant hurdles. Additionally, achieving selective targeting while minimizing non-specific interactions remains a critical challenge. The regulatory landscape for nanomedicine is still evolving, creating uncertainty in safety assessments and approval processes. In order to overcome these challenges, successfully incorporate nanoparticles into standard medical practice, and eventually enhance patient outcomes, more research and innovation will be required. By increasing medication administration precision, efficacy, and safety, the use of nanoparticles in medicine delivery holds the potential to completely transform the healthcare system as it exists today.

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Received on 28.01.2025 Revised on 16.03.2025

Accepted on 22.04.2025 Published on 09.05.2025

Available online from May 12, 2025

Res. J. Pharma. Dosage Forms and Tech.2025; 17(2):115-122.

DOI: 10.52711/0975-4377.2025.00017

This work is licensed under a Creative Commons Attribution-Non Commercial-Share Alike 4.0 International License. Creative Commons License.