INTRODUCTION:

The low oral absorption of flavonoids, tannins, and terpenoids, among other active components present in medicinal plants, limits their pharmacological action and potential therapeutic value.¹

Two factors contribute to the poor absorption of active phytochemicals: Polyphenols' multi-ring architectures prevent them from being absorbed passively or non-actively, and active compounds' limited solubility in water or lipids prevents them from getting through the gastrointestinal cells' outer membrane². One effective way to increase the bioavailability of active components among the various drug delivery systems is by the use of phytotomies, also known as "Phyto-phospholipid complexes," "Supra-molecular complexes," and "Herodoms".²The Phytosome, which surrounds the medication's active ingredient like an envelope, shields it from microbial and digestive fluid breakdown. Significant healthcare sectors, such as the medical community, chemists, doctors, and nurses.³ Herbal medicine will continue to grow in popularity globally for a number of reasons. Therefore, there is an immediate requirement for accurate and thorough information regarding Herbal medicine, especially with regard to formulation, safety, toxicity, efficacy, regulation, research and development, analytical methods, quality control, and economic value.⁴Plant substances linked to cancer treatment include quercetin or rutin, taxes, genistein, camptothecin, and epipodophyllotoxins. Compared to allopathic drugs, which are helpful in the treatment of cancer, these herbal therapies have fewer negative effects.^5,6,7,2When administering herbal medications, innovative drug delivery methods have several benefits over traditional formulations.⁷In order to ensure that the medication reaches the intended site of action and has therapeutic benefits, it is given to the patient at the recommended dosage.⁸The preparation is frequently referred to as a medication delivery system or dosage form. The drugs are supplied in a suitable formulation that takes into account a number of variables, including acceptability, effectiveness, and safety.

The development of dosage forms has paralleled advances in all fields of science and engineering, moving from straightforward mixes and tablets to extraordinarily complex, high-tech drug delivery systems, or NDDSs.²Herbs contain more than fifteen primary phytochemical classes, such as compounds, alkaloids, glycosides, polysaccharides, volatile oils, tars, phytochromes, natural acids, amino acids, tannins, proteins, and so on.⁹ There are several unique chemical entities in each group. It's possible that the aggravating factors in natural remedies work in concert with one another. Therefore, to maximize the economic importance of herbal medications, it is essential to leverage these synergistic effects.¹⁰

Figure 1: Challenges in conventional drug delivery system.

Nano formulations for Herbal Drug Delivery:

In order to improve bioavailability, targeted distribution, controlled release, and particle size reduction to the nanoscale, herbal medication release is achieved using nano formulation. Combination therapy is made possible by nanoparticles, which shield medications from deterioration. Among the most important factors are safety and biocompatibility. Commercialization requires scalability and cost-effectiveness. In general, herbal medicine administration is optimized by nano formulation, which raises therapeutic potential and efficacy. The potential of nano-formulations for drug administration has been the subject of increased attention.¹¹ Among these nano-formulations are polymeric nanoparticles, liposomes, ectosomes, nano-emulsions, transferosomes, and phytotomies. These natural substrates can be made more bioavailable by using nano formulations, which are an efficient way to get around these issues.¹² These Nano formulation have been used in drug delivery studies to reduce side effects and increase medication bioavailability, solubility, extended blood circulation, and targeted delivery. NFs may interact with biological systems after entering the body by injection, ingestion, skin penetration, or inhalation.¹¹ NF design shields the substance being delivered from environmental elements like pH, enzymes, and biochemical degradation, increasing the likelihood that it will reach the site of action following injection. Furthermore, through site-specific release and targeted distribution, NFs can reduce administration doses while improving the therapeutic effects of medications.¹³

Figure 2: Various types of nanoparticles used for herbal drug delivery

Types of Nanoparticles Used for Herbal Drug delivery:

Nanoparticles

Herbal preparations that are well-organized to release both hydrophilic and hydrophobic components are known as nanomolecules. Nanoparticles are parts with a nanoscale size of 10–1000mm.¹⁴ Forming nanomolecules as a release technique aims to target-specifically deliver pharmaceuticals at the most therapeutically suitable rates and dosing regimens by controlling particle size, surface characteristics, and biochemical component release.¹⁵ Numerous contemporary NDDS applications based on nanotechnology may enhance post-administration drug composition changes in body systems and aid in diagnosis, therapy, and monitoring.^16,17,73In recent years, herbal medications maintain a prominent place in the pharmaceutical sector because of their well-established benefits and extremely low negative effects. In addition, compared to synthetic pharmaceuticals, herbal medicines have a symmetrical method of interest to generate nanoparticles.¹⁸ Herbal medication can be targeted using nanoparticles to a specific organ, improving its solubility, safety, efficacy, selectivity, and frequency of dosage.¹⁸Pharmaceutical scientists are currently focusing on creating a DDS for natural medications using scientific techniques. One well-known traditional Chinese medicine for supporting the liver and kidneys is Cuscuta chinensis. Numerous phytochemicals found in herbs can only be dissolved in non-polar solvents. Oral administration of the substance may result in limited absorption due to the poor water solubility of its principal constituents, which include tannin, saponin, flavonoids, lignans, and alkaloids. As a result, nanoparticles were created as a means of delivering the extract of these plants to the intended location.^19,74

Figure 3: Transport of drug molecule through skin

Liposomes:

These are colloidal or microparticulate carriers that spontaneously develop when specific lipids are hydrated in aqueous solutions. Their diameters typically range from 0.05 to 5.0μm.⁹ Encasing part of the solvent, the liposomes are spherical particles that freely travel throughout or float into their interior. One, several, or more concentric membranes may be carried by them. Polar lipids, which are made up of the identical molecules in both hydrophilic and lipophilic groups, are the building blocks of liposomes. When polar lipids come into contact with water, they self-layup and create self-organized colloidal particles.²⁰ Liposome-based drug delivery systems can raise the therapeutic index of anticancer medicines by either boosting the drug concentration in tumour cells or lowering the exposure in normal tissues by utilizing targeting strategies or the improved permeability and retention effect phenomenon.²¹ The main advantages of using liposomes are their high biocompatibility, ease of preparation, chemical versatility that allows hydrophilic, amphiphilic, and lipophilic compounds to be loaded, and simple manipulation of pharmacokinetic properties through simple adjustments to player component composition.

One of the bioflavonoids that has been researched the most recently is curcumin; numerous studies have demonstrated its anti-inflammatory, anticancer, chemoprotective, antioxidant, and gastroprotective qualities.²²

Although curcumin is a naturally occurring molecule with numerous anticancer effects and tumour cell selectivity, its water solubility and bioavailability are low. By protecting curcumin from enzymatic breakdown, liposomes enhance its therapeutic index, and surface modification promotes the long-term circulation of polyethylene glycol (PEG). A wide variety of curcumin's anti-cancer activities include tumour blocking, preventing tumour development, and inhibiting invasion and metastasis.^23,75

Figure 4: Liposome

Ethosome:

The invention of the ethosomal patch, which comprises of medication in ethosomes, is the result of more recent advances in patch technology. Soy phosphatidylcholine, ethanol, and water comprise ethosomal systems. They have a great capacity for trapping of various lipophilic particles and can form multilamellar vesicles. Elastic vesicles and transfersomes have also been used as drug carriers for a range of tiny chemicals, peptides, proteins, and vaccines.²² Better medication distribution through the skin is made possible by emmetropes' capacity to fully penetrate the skin due to their deformability and high entrapment efficiency.

The physical and chemical properties of ethosomes, in contrast to other liposomes, allow the medication to legally pass past the stratum corneum and enter a deeper layer of skin or even the bloodstream.²³ This quality is essential to the topical medicine carrier and transdermal administration system. Furthermore, the ethosomes carrier can effectively deliver hydrophilic and lipophilic drugs within cells²⁴, enhance the percutaneous absorption of matrine, a herbal remedy that reduces inflammation⁷¹, and facilitate the easy penetration of antibacterial peptides into fibrocytes.²⁵ They have higher deformability and entrapment efficiency, can facilitate drug release by skin penetration, and deeply penetrate the skin. The characteristics of ethosomes, similar to those of other liposomes, permit the lawful passage of medications past the stratum corneum into the skin's deeper layers or even into the bloodstream.²⁶ Extremely significant as a mode of delivery. Ethosome transporters can also suggest a well-organized intracellular release of medications that are both lipophilic and hydrophilic.²⁷ Matrine, an anti-inflammatory herbal medication, reaches the fibrocytes with improved percutaneous absorption.^28,77-79

Figure 5: Ethosome

Nano-Emulsions:

Two distinct liquid kinds that are incompatible with one another are combined to create an emulsion, a non-homogeneous dispersion system that disperses as droplets in the other.²⁴While the micro-emulsion is also referred to as a nanoemulsion, the sub-micro-emulsion is also called a lipid emulsion. Emulsion provides targeted drug delivery in vivo due to its lymphatic affinity. Moreover, the drug can have a long-lasting sustained release since it is contained in the inner phase and kept away from the body and tissue fluid.²⁵ Emulsifying the herbal medication will not only provide the desired sustained release but also improve drug penetration into the skin and mucous membranes, stabilize the hydrolyzed materials, and reduce the stimulating effect of the medication on tissues. So far, a few different kinds of herbal medicines, such as camptothecin, brucea javanica oil, coixenolide oil, and zedoary oil, have been used to create emulsions. For example, Zhou et al.²⁶ Bioavailability of the drug is improved by oral delivery. When injected subcutaneously or intramuscularly, the hydrophilic compounds have a higher permeability and condense into the lymphatic system.²⁷ Recent years have seen the development of novel systems via Nanoemulsion (NE), such as Transcuto P and alkyl polyglycosides. Natural herbal treatments such brucea javanica oil, rutin, genistein, and coixenolide have been combined with NE for specific purposes. The antioxidant potential of Syagrus romanzoffiana (Cham.) Glassman, fruit O/W (oil in water) NE, is assessed using the phase inversion technique.²⁸ For targeted cancer therapy, paclitaxel nanoemulsion with tocopherol as the oil phase has been created and is undergoing phase 3 clinical trials (NCT01620190).²⁹ A controlled cross-over trial that was double-blinded and randomized was used to examine the impact of eugenol nanoemulsion on pain.^30,80

Transferosomes:

These are specifically designed particles or vesicles with the capacity to offset environmental stress by undergoing brief, energetically beneficial changes.³¹ Transfersome-related novel tactics are proliferating. By facilitating the diffusion of bigger molecules over the stratum corneum, it has contributed to the come out over the drug delivery catastrophe, which is now impossible. These pliable vesicles are capable of transporting big molecules that are several times smaller than their own length via the skin's numerous pores.^32,33 Transferosomes applied non-occluded to the skin can pass through the lipid lamellar sections of the stratum corneum because of osmotic force or skin moisture. It can be utilized as a medication carrier for different peptides, proteins, tiny molecules, and ingredients found in herbs. Transferosomes can penetrate the stratum corneum and supply the nutrients the skin needs on a localized basis to stay healthy.³⁴ In this regard, Xiao-Ying et al. have developed capsaicin transferosomes.³⁵ As a transdermal delivery system and topical medication carrier, this feature is crucial. Furthermore, the ethosomes carrier can effectively deliver hydrophilic and lipophilic drugs within cells,^36,37 enhance the percutaneous absorption of matrine, a herbal remedy that reduces inflammation, and make it easier for the antibacterial peptide to enter fibrocytes.³⁸ Transfersome is a highly adaptive and dynamic aggregate that reacts to stress. It's a pliable vesicle with an aqueous core encircled by the intricate fat bilayer. The bilayer's shape and local composition determine the vesicle. Self-control in addition to self-improvement. This facilitates the client's ability to pass through various obstacles with ease and subsequently function as a non-intrusive target medication transport agent.

Phytosome:

While some words indicate cell-like, the word "Phyto" indicates plants. "Phyto" refers to a plant. Phytosomes were a vesicular delivery system for phytoelectric substances found in herbal extracts and lipid-binding (one molecular phyto-constituent bonded to at least one molecular phospholipid). Phytosomes prevent vital components of herbal extracts from degrading gut bacteria that have enhanced absorption and digestive secretions offers enhanced biological, pharmacokinetic, and pharmacological properties as well as increased availability parameters of a traditional herbal extract as well as the differences between liposomes and phytosomes.^39,76

Figure 6: Phytosome

Due to their intrinsic restriction of relatively large molecular size, water-soluble phytocompounds are poorly absorbed in phospholipid structures. This is because their low lipid solubility and limited ability to pass across the lipid-rich biological membrane lead to poor encapsulation efficacy and bioavailability. Polar phytocompounds make up a significant portion of bioactive phytocompounds. In order to address these issues, scientists have created phytosomes, which increase the water-soluble BPCs' bioavailability.^40,41 The patented technology known as "Phytosome" was developed by a well-known manufacturer of pharmaceuticals and nutraceuticals. It combines phospholipids with standardized plant extracts or water soluble phytoconstituents to create lipid-compatible molecular complexes known as "phytosomes," which dramatically increase absorption and bioavailability.⁴² Oral consumption of flavonoids, which make up the majority of the active elements in herbal medications, lowers their blood levels. Phytosomes are lipid-compatible molecular complexes that are generated from water-soluble active components, primarily polyphenols. Compared to basic plant extracts, these are more stable in eluding the lipophilic plasma membrane and eventually reaching the target organs, leading to increased blood levels. Phosphatidylcholines, which are hydrophobic molecules generated from soy, are the main component of a balanced lipid active ingredient.⁴³ While phytosomal complexes were initially studied for cosmetic purposes, over the past few years, increasing amounts of evidence have emerged suggesting their potential for drug delivery, with benefits in the areas of anticancer, hepatoprotective, cardiovascular, and anti-inflammatory applications.⁴⁴

The pharmacokinetics and therapeutic characteristics of phytosome complexes are superior to those of their noncomplex herbal extract. The bioavailability of certain phytochemicals has been significantly increased via phytosome technology.⁴⁵ The majority of phytosomal research is on Silybum marianum because it has superior flavonoids that protect the liver. Hepatoprotective qualities are known to be possessed by the flavonoids present in the fruit of the milk thistle plant (Spatharianum, Family Sterraceae). Silymarin treatment has been shown to be effective for a number of liver diseases, such as cirrhosis, hepatitis, fatty infiltration of the liver (fatty liver generated by chemicals and alcohol), and inflammation of the bile duct. The liver's resilience to harmful shocks is significantly increased by silymarin's antioxidant capacity.⁴⁶

Three flavonoids of the flavonol subclass—which have a fully saturated C-ring—are the main components of silymarin. The most common is silybin, which is followed by silydianin and silychristin. In reality, silybin is a flavonolignan, most likely created by the plant through the fusion of a coniferyl alcohol and a flavonol. The most effective of the three is currently understood to be silybin.⁴⁷

Microencapsulation Techniques:

In a variety of industries, including food, medicine, and cosmetics, microencapsulation techniques like solvent evaporation, coacervation, and spray drying are essential. By encasing active ingredients in a protective shell, these methods improve stability, controlled release, and targeted distribution. Among the most popular techniques is spray drying, which involves atomizing an active component solution or suspension and encasing material in tiny droplets that are subsequently dried to form solid microcapsules.⁵⁰ However, in order to generate a coacervate phase around the active ingredient, coacervation depends on the phase separation of proteins or polymers, which is then followed by solidification to form microcapsules.⁴⁸ By dissolving the encapsulating material and active component in a volatile solvent, and then removing the solvent, microcapsules are produced (solvent evaporation).⁴⁹ Based on variables including the active ingredient's nature, the desired release profile, and the intended use, a particular approach is chosen. Each method has unique benefits. These industrial uses, which include fertilizers in the agro industry, pharmaceuticals in the pharma sector, and the controlled release of citric acid in the food business, endeavor to slow down the rate at which the core leaves the microcapsule rather than completely isolate it. With several benefits like increased stability, increased bioavailability, controlled release, and targeted distribution, microencapsulation has become a useful method in the field of herbal medicine delivery.⁵¹ For example, a lot of research has been done on the microencapsulation of curcumin, the active ingredient in turmeric, to address its low bioavailability and poor aqueous solubility. Curcumin can be enclosed within a polymer matrix using methods like coacervation or spray drying, which improves its solubility and protects it from degradation. Better therapeutic results result from increased absorption and bioavailability of the substance in the body.

1. Enhanced Bioavailability: Due to issues like limited solubility or quick metabolism, herbal actives frequently have poor bioavailability. Microencapsulation provides a solution to this problem. Herbal chemicals are made more soluble, stable, and absorbable in the body through the process of microencapsulation, which encases them in a protective matrix. Higher bioavailability as a result makes it possible to use the medicinal ingredients more effectively.⁵³

2. Controlled Release: The capacity of microencapsulation to produce a gradual, regulated release of herbal actives is one of its main benefits. The release profile of the active substances can be adjusted to fulfil particular therapeutic needs by utilizing suitable polymers and encapsulating techniques. For ailments that need long-term care, this controlled release assures a steady supply of herbal ingredients, preserving therapeutic levels in the body and extending their activity.⁵²

These benefits demonstrate how microencapsulation might be a useful technique for increasing the bioavailability and regulated release of herbal active ingredients, which will ultimately improve the effectiveness and therapeutic results of herbal drugs.

Phyto-Phospholipid Complexes:

Possible Mechanism of Phyto-Phospholipid Complexes:

The reason for the decreased absorption of the extract or phytoconstituents is because of their bigger molecular size and less ability to mix well with lipids or oils. Simple diffusion is unable to absorb the greater size of the active ingredients from the intestines into the blood. Moreover, the active components' lipid insoluble nature limits their ability to cross the lipid-rich outer biological membranes of the small intestine, which comprise enterocyte cells. The development of Phyto-Phospholipid Complexes aimed to address these issues and enhance bioavailability. A specific amount of phosphatidylcholine, a phospholipid, is reacted with an extract or phytoconstituent (such as simple flavonoids) in a non-polar solvent to form phyto-phospholipid complexes. Phosphatidylcholine possesses two distinct molecular properties: the hydrophilic choline moiety and the lipophilic phosphatidyl moiety. The lipid-soluble phosphatidyl portion of the phosphatidylcholine molecule, which is made up of the body and tail, surrounds the choline-binding material, holding the extract or phytoconstituents in place. Consequently, a phyto-phospholipid complex—a phospholipid-containing lipid-compatible molecular compound—is created by the extract or phytoconstituents. The results of the chemical analysis show that a phytosome is often a plant active that is connected to at least one phosphatidylcholine molecule. The ensuing phyto-phospholipid combination resembles a tiny microsphere or cell that can pass through intestinal membranes with ease and increase the drug's bioavailability (fig. 7).⁵⁴

Figure 7: Possible Mechanism of Phyto-Phospholipid Complexes

Phospholipid Complex and their Absorption:

Enterocyte-based transport from the GIT can be used to absorb phospholipid complexes, and medications can be moved from the intestinal lymphatic system—which is extensively dispersed throughout the body—to the systemic circulation. The ability to avoid first-pass metabolism and use lymphatic transport for tailored medication administration is its main benefit.^55,56 Diagram showing the potential pathways by which the phyto-phospholipid complex enters the gut from the unstimulated water layer: direct solubilization through enterocytes; paracellular transport in lateral tight junctions; blocking transporter proteins to prevent drug efflux; production of chylomicrons; and lymphatic port entry. Reported improved bioavailability of Phyto-Phospholipid Complexes Drug bioavailability is improved by phytosomes because of their reduced size and lipophilic characteristics. Phyto-Phospholipid Complexes have been scientifically verified by multiple researches to exhibit superior therapeutic and pharmacokinetic properties when compared to traditional dose forms.

Transdermal Drug Delivery for Herbal Therapy:

The most popular drug delivery method is the conventional dosage form, such as tablets and capsules; nevertheless, both dosage forms have issues with gastric drug/enzyme instability that arise during first pass digestion. Numerous other issues with the oral route include bad taste, odor, and color. Problems during therapy are a result of the numerous extra issues that arise when taking medicines. Patients can occasionally stop complying. Transdermal patches are non-invasive and non-irritating, and TDDS patches are utilized with continuous release medications, which exhibit their effects for a precise amount of time. It is a compelling substitute method for more traditional methods when it comes to systemic drug administration.⁵⁷-⁶⁸ Transdermal drug delivery, which is distinct from conventional topical drug delivery, is the process of delivering a drug via the skin to produce a systemic impact.⁶⁹ Transdermal delivery of comprehensive morphological, biophysical, and physicochemical drugs offers a significant advantage over oral and injectable routes in terms of delivering therapeutic agents through the human skin for systemic effects. This is because it avoids first pass metabolism and increases patient compliance, respectively.⁷⁰ A lot of interest has been shown in transdermal drug delivery systems over the past ten years due to their many benefits over oral controlled release delivery systems and conventional dosage forms, particularly their ability to improve patient compliance, avoid hepatic first pass effect, reduce gastrointestinal side effects, and require less frequent administration.⁷¹ Transdermal drug delivery systems are characterized as discrete, self-contained dosage forms that, when applied to intact skin, allow the drug to be delivered.

CONCLUSION:

The process of using microencapsulation to optimize herbal medicine delivery systems has advanced the field and revealed exciting new directions for research. Microencapsulation has many advantages that go beyond improving a drug's characteristics; it also presents chances for new therapeutic treatments and approaches to managing diseases. In order to optimize delivery systems for optimal efficacy, it will be necessary to go deeper into understanding the complex interactions between herbal actives and encapsulating matrices in the future. Furthermore, investigating the possibilities of innovative methods of delivery like stimuli-responsive microcapsules and lipid-based nanoparticles holds significant promise for precisely controlling drug release kinetics and targeted distribution. Adopting a comprehensive strategy that incorporates knowledge from the fields of biotechnology, materials science, and pharmacology will be crucial in advancing the development of herbal medicine delivery. Furthermore, in order to ensure that innovative ideas are converted into clinically feasible treatments, it is necessary to cultivate cooperative relationships between academics, industry, and regulatory bodies. Through a combination of teamwork, creativity, and multidisciplinary research, we can fully utilize herbal medicines to address urgent healthcare issues and enhance people's quality of life all around the world.

ACKNOWLEDGEMENT:

Authors are thankful to Principal Dr. H. N. More, Bharati Vidyapeeth College of Pharmacy, Kolhapur for providing the facilities for the work.

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Received on 20.03.2025 Revised on 04.07.2025

Accepted on 16.10.2025 Published on 20.05.2026

Available online from May 25, 2026

Research J. Pharmacy and Technology. 2026;19(5):2214-2222.

DOI: 10.52711/0974-360X.2026.00319

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