Herbal Medicine Meets Nanotechnology: A Transformative Approach

Dhananjay A. Deore¹*, Sushant M. Ahire¹, Sunil K. Mahajan²

¹Department of Pharmaceutics, Divine College of Pharmacy, Satana, India.

Savitribai Phule Pune University, Pune, 423301, Maharashtra, India.

²Principal, Divine College of Pharmacy, Satana, India.

*Corresponding Author E-mail: deored680@gmail.com, sushantahire071@gmail.com, divinecop15@gmail.com

ABSTRACT:

All around the world, herbal remedies have been widely used since ancient times. The usage of herbal medicines has increased due to their ability to treat a wide range of conditions with fewer side effects. For many types of medicinal plants to work, active compounds must be present. It is possible to deliver the active component to the targeted site of action at a concentration high enough to last the entire course of treatment by using nanosystems. Conventional therapy does not meet these requirements. Reviewing the use of nanotechnology in herbal medicine is the goal of this study.

KEYWORDS: Nanotechnology, Herbal medicine.

1. INTRODUCTION:

One of the traditional medicinal disciplines used in India is ayurveda¹. Due to their possible therapeutic impact and lower side effect rate when compared to other medications, herbal medicines have gained recognition from both medical professionals and patients^2,3. Additionally, they boost the medicine's bioavailability⁴. One of the more important NDDS is thought to be nanoparticles. By targeting certain organs with nanoparticles, herbal medicines can improve their focused medication delivery, efficacy, and safety.

1.1 Nanotechnology in herbal drugs:

The particle diameter of the nanoscale system is 0.1 m, or submicrometer.

Researchers are studying this nanotechnology more and more since it offers numerous benefits related to different factors, such as the route of administration and improved therapeutic effects. Herbal medications with delivery methods based on nanotechnology have a lot of promise and special qualities⁵.

Fig. 1: Diagram illustrate the phytochemicals' shortcomings that restrict their use medicine ^6-9

1.2 Mechanisms of Absorption in Nanotechnology:

The size of the particles has a big impact on how the nanoparticles work¹⁰. Particles larger than 300nm often disperse throughout the blood, while those less than 100 nm go into tissues¹¹. It is necessary to take into account additional variables, like the charges and solubility of the particles¹². It has been demonstrated that there are several ways to induce the effects of nanoparticles, such as by eating or inhalation¹³.

1.3 Various drug delivery methods utilizing nanotechnology:

1.3.1 Polymeric nanoparticles:

Researchers are now concentrating on the nanotechnological uses of medicinal plants, and they have created a number of novel delivery vehicles, such as polymeric nanoparticles.¹⁴. Nanoparticles are also beneficial when used in blood since they are stable, non-toxic, non-thrombogenic, non-immunogenic, non-inflammatory, do not activate neutrophils, and do not penetrate the reticuloendothelial system. Sometimes, polymeric nanoparticles are used to access specific tissues or as a cell surface.^15–18.

1.3.2 Solid lipid Nanoparticles and Nanostructured lipid carriers:

Solid lipid nanoparticles (SLNs), colloidal carrier systems that reduce or do away with some of the drawbacks of conventional colloidal drug delivery systems, such as emulsions, liposomes, and polymeric nanoparticles, were developed in the early 1990s.¹⁹. In addition to being more easily generated on a wide scale, SLNs offer superior protection against the degradation of labile medicines due to their higher physicochemical stability²⁰. SLNs are colloidal particles composed mostly of highly purified triglycerides and room-temperature solid lipids²¹.

1.3.3 Liquid crystalline systems:

Between a crystalline solid and an isotropic liquid, there is a special phase of condensed structures called liquid crystals; their ease of efflux reveals whether they are disordered or ordered. Mesophases are states of matter in between solids and liquids; they can be cubic or hexagonal in LCs^22–23. Functional unit micelles are amphiphilic molecular aggregates seen in LLCs. Amphiphiles possess a big (hydrophobic) polar tail and a small polar (hydrophilic) portion^24–25.

1.3.4 Liposomes and microemulsions:

Liposomes are tiny vesicles made up of one or more concentric lipid bilayers separated by aqueous media. Hydrophilic substances are contained in the aqueous compartment, whereas adsorbed lipophiles are introduced into the membrane. Both types of material can also be enclosed as an alternative. After being titrated until it became clear, the fluid system was first semi-transparent^26–27. MEs are reservoir systems that require an interface or membrane to be swapped in order to control the drug's release into the environment once it has been extracted from the dissolving media²⁸.

Fig:2. Types of nanoparticles used for drug delivery

2. FORMULATION CONSIDERATIONS:

Table:1. Nanotechnology formulation.

Sr. No	Ingredient	Amount	Function	Nanotechnology Application
1.	Curcumin Extract	100 mg	Active ingredient	Encapsulated in nanoparticles
2.	Polyvinyl Alcohol (PVA)	50 mg	Stabilizer	Used to form nanoparticles
3.	Chitosan	30 mg	Biocompatible carrier	Nanoparticle formulation
4.	Phospholipids (Lecithin)	20 mg	Enhance bioavailability	Liposomal encapsulation
5.	Silver Nanoparticles	10 mg	Antimicrobial activity	Incorporation for enhanced efficacy
6.	Water (Distilled)	10 mL	Solvent	Solvent for formulation
7.	Sodium Chloride (NaCl)	0.9% (w/v)	Isotonicity adjustment	Stabilizes formulation

A. FORMULATION ASPECTS FOR NANOTECHNOLOGY IN HERBAL MEDICINE:

1. Active ingredients: Utilizing different active components in order to boost the bioavailability and therapeutic benefits of herbal substances is a common application of nanotechnology in herbal medicine. Several often-investigated active compounds include of:

I. Curcumin: An antioxidant and anti-inflammatory compound, curcumin is found in turmeric. Its solubility and bioavailability can be increased by nanoparticle compositions²⁹.

2. Stabilizers: -These are various stabilizers commonly used in the formulation of nanotechnology in herbal medicine.

I. Polyvinyl Alcohol (PVA): Because of its biocompatibility and capacity to form films, PVA is a synthetic polymer that is frequently utilized as a stabilizer for nanoparticles³⁰.

3.Biocompatible Carriers: The formulation of nanotechnology in herbal medicine frequently makes use of a variety of biocompatible carriers. Several biocompatible carriers are used in the nanotechnology formulation for herbal medicine.

I. Liposomes: Lipid bilayer-based spherical vesicles that are effective at encasing both lipophilic and hydrophilic medications.

4. Bioavailability Enhancers: In herbal medicine, several bioavailability enhancers are frequently used into nanotechnology formulations.

I. Piperine: An alkaloid presents in black pepper that inhibits metabolic enzymes to increase the bioavailability of certain herbal ingredients.

5. Antimicrobial Activity: Many antimicrobial agents are commonly used in the development of nanotechnology in herbal medicine, including:

I. Silver Nanoparticles: Silver nanoparticles are known for their broad-spectrum antimicrobial effect and are often added to formulations to enhance the antibacterial and fungal qualities of herbal extracts.

6. Solvents: Many solvents are frequently employed in the manufacture of herbal medicine using nanotechnology.

I. Ethanol: Because it can dissolve a variety of phytochemicals, it is often employed to extract bioactive components from botanical materials.

7. ISOTONICITY Adjustments: The formulation of nanotechnology in herbal medicine employs a variety of isotonicity adjustment techniques.

I. Sodium Chloride: Added to formulations to match the osmotic pressure of body fluids, sodium chloride is the most widely used chemical to alter isotonicity.

3. MANUFACTURING METHODS:

3.1. Solvent Evaporation:³¹

A popular approach for creating nanoparticles is solvent evaporation, particularly for uses in herbal medicine and medication delivery.

Steps:

· Preparation of the Solution:

Dissolution: A volatile organic solvent (such as ethanol, acetone, or chloroform) is used to dissolve herbal extracts or active medicinal components. The chemicals of interest should be efficiently solubilized by the solvent.

Concentration: Determining the ultimate size and dispersion of nanoparticles depends critically on the concentration of the active chemicals.

· Evaporation Process:

Heat Application:

Either heat or lower pressure is applied to the solution. In order to facilitate solvent removal, the solution can be gently heated in a rotating evaporator while the pressure is decreased.

Controlled Environment: Temperature and pressure adjustments can be used to fine-tune the evaporation rate, which facilitates the creation of nanoparticles.

· Nucleation and Growth:

Supersaturation results from an increase in the solute's concentration when the solvent evaporates.

Nucleation: The formation of the first particles happens when nucleation reaches a particular threshold. Growth: As more solute molecules gather around these nuclei, they expand into nanoparticles.

· Stabilization:

Stabilizers (such as surfactants or polymers) can be applied either during or after the evaporation process to guarantee a steady dispersion of nanoparticles and prevent agglomeration.

This stage improves the formulation's stability and aids in maintaining the intended particle size.

· Collection and Characterization:

Centrifugation or filtration are used to gather the resultant nanoparticles.

To analyze particle size, shape, and distribution, characterisation methods like scanning electron microscopy and dynamic light scattering are used.

Fig:3. The solvent evaporation technique.

3.2 Coacervation:³²

An advanced approach for creating nanoparticles, the coacervation process is very useful when used in conjunction with herbal medicine.

· Preparation of Polymer Solution:

The first step in the procedure is to dissolve the relevant polymers in a solvent, such as synthetic polymers or natural polymers like gelatin or chitosan. The polymers chosen must be compatible with the herbal extracts being used, which makes selection critical.

· Addition of Herbal Extract:

The polymer solution is supplemented with the herbal extract that contains the targeted bioactive components. To maximize the encapsulation efficiency, the extract concentration is changed.

· Inducing Coacervation:

Usually, the addition of a non-solvent (like alcohol) or changes to the surrounding environment (pH, temperature, etc.) cause a concentration to increase. As a result, the polymers phase-separate and produce herbal compound-containing coacervate droplets.

· Formation of Nanoparticles:

Solid nanoparticles can be formed from the coacervate droplets by stabilizing or hardening them with crosslinking chemicals. To keep the nanoparticles' structural integrity intact, this step is crucial.

· Purification and Characterization:

To get rid of other contaminants and unencapsulated herbal ingredients, the resultant nanoparticles are purified. Methods like centrifugation and dialysis are frequently employed.

Characterization methods including dynamic light scattering and scanning electron microscopy are used to assess the size, shape, and encapsulation efficiency of particles.

Fig:4. Coacervation technique.

3.3 Electrospraying: ³³

Using a high voltage electric field, electrospraying is a technique for creating micro- and nanoparticles (capsules or spheres).

Steps:

· Preparation of the Solution:

The herbal extract containing the targeted bioactive components is dissolved in a volatile solvent together with a suitable polymer (e.g., poly (lactic-co-glycolic acid) [PLGA], chitosan). For efficient encapsulation, the polymer and extract concentrations are adjusted.

· Electrospraying Process:

The syringe is filled with the polymer solution and attached to a nozzle. The nozzle and collection plate are subjected to a high-voltage electric field.

A jet of the solution is released from the Taylor cone that the solution at the nozzle tip develops as the voltage rises. Solid nanoparticles are formed when the solvent starts to evaporate while the droplets are in flight.

· Collection:

The collection plate attracts the charged droplets, which settle there and congeal into nanoparticles or nanofibers.

Particle size and morphology can be controlled by varying the applied voltage and the distance between the nozzle and the collection.

· Characterization:

The resulting nanoparticles' size, shape, and distribution are investigated using techniques including scanning electron microscopy (SEM) and dynamic light scattering (DLS). The encapsulation efficiency and release patterns of the bioactive compounds are also assessed.

Fig:5. Electrospraying technique

3.4 Ball Milling:³⁴

A top-down synthesis method that splits apart big molecules into smaller ones to produce nanomaterials.

Process Parameters:

· Ball Material: The purity of the finished product is impacted by the ball material selection. Ceramic and stainless steel are popular options.

· Rotation Speed: Although faster speeds produce more impact force, they can also produce too much heat, which could damage delicate materials.

· Ball-to-Powder Ratio: A perfect ratio reduces contamination while increasing size reduction effectiveness.

· Milling Time: Finer particles can be produced by extended milling, although this must be weighed against the possibility of heat damage.

Fig:6. Ball milling technique

4. EVALUATION:

Examining the efficacy, safety, and bioavailability of herbal substances through nanoformulations is a major emphasis of the evaluation of nanotechnology in herbal medicine.

4.1 Chemical parameters:

A. Toxicity Assessment:

1. In Vitro Characterization:

As part of early preclinical development, the biocompatibility of blood components must be evaluated in vitro. Numerous studies have documented the hemolytic characteristics of NPs. It is likely that physicochemical factors that are not frequently taken into account in toxicity screening investigations influence the biological activity of NPs.

2. Assay for In Vitro Cell-Based Cytotoxicity:

The goals of in vitro biological tests are to investigate the biological characteristics of nanoparticles (NPs), detect interferences caused by them, and offer the first thorough understanding of the possible causes of these interferences. They also highlight how crucial it is to characterize the physicochemical properties of NP formulations.

3. In Vivo Studies:

Using animal models, such as non-human primates, in vivo investigations provide insights into biological interactions in living species. The main methods used to evaluate the toxicity of nanomaterials are these tests. They can ascertain whether NPs are cytotoxic or organotoxic to a particular organism. This assay can be used to determine the cellular absorption, distribution, metabolism, and elimination of nanomaterials³⁵.

4.2 Physical parameters:

1. Effect of Size:

The size of nanoparticles has a major impact on their pharmacokinetics, therapeutic effectiveness, in vivo biodistribution, and tumor accumulation³⁶. NPs can passively accumulate in tumors based on their size due to the EPR effect and the different pore sizes of tumor arteries. When compared to healthy tissues, the EPR effect increases NP deposition by more than 50 times³⁷. NPs are eliminated by the mononuclear phagocytic cells in the RES of the liver and spleen, resulting in a sufficient accumulation at the target location³⁸.

2. Effect of Shape:

Another important aspect of NPs that can have a big impact on how they function in biomedical applications is their form. Non-spherical particles have gained interest recently, despite the fact that spherical NPs are used in the majority of laboratory-scale investigations and clinical trials³⁹. For polymeric nanoparticles, templates or post-synthesis manipulation can be used to create nanowires, nanorods, nanocubes, nanobelts, nanostars, nanothorns, and other shapes⁴⁰.

3. Effect of Surface Charge:

Surface charge can have a major effect on NPs' efficiency and in vivo fate⁴¹. Different surface densities and charges (positive, neutral, or negative) exist for each NP. Neutrally and negatively charged NPs typically have superior biocompatibility, longer circulation half-lives, more stealth-like actions, and lower unwanted clearance.

4. Effect of Surface Functionality:

It is astonishing how much better NPs perform and can be used in biomedical applications when they have functional groups on their surface. By modifying their functional groups, functionalized nanoparticles (NPs) can attain improved targeting and delivery, as well as improved biocompatibility as compared to pure nanomaterials.

5. Effect of Hydrophobicity:

The hydrophobicity of NPs has a significant role in how they interact with biological barriers. For example, Porret et al. evaluated the interactions of a variety of AuNCs (metal core ~1–1.5nm) with (i) serum in solution, (ii) a lipid bilayer model system integrated into a microfluidic apparatus, and (iii) different cell types (A375 melanoma cells and U87MG human primary glioma cells).

6. Effect of Aggregation:

Compared to properties like size, shape, and surface chemistry, the effects of nanoparticle aggregation have received far less attention. Exposure to biomolecules such as proteins and ions can cause NPs to cluster under cell culture conditions, which can greatly increase the risk of toxicological side effects in biomedical applications.

5. CONCLUSION:

An exciting new avenue for improving the security and effectiveness of conventional herbal treatments is the application of nanotechnology to herbal medicine. Nanotechnology has the potential to optimize therapeutic outcomes while minimizing negative effects by enhancing the bioavailability, targeted administration, and controlled release of active substances. However, in order to fully exploit the potential of nanotechnology in herbal medicine, additional study is necessary to solve safety, regulatory, and ethical concerns. Better health outcomes could result from this multidisciplinary approach's potential to bridge the knowledge gap between conventional wisdom and emerging research.

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Received on 23.01.2025      Revised on 28.02.2025

Accepted on 03.04.2025 Published on 10.07.2025

Available online from July 17, 2025

Asian J. Pharm. Res. 2025; 15(3):302-308.

DOI: 10.52711/2231-5691.2025.00047

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