A Novel Targeted Drug Delivery Carrier: Herbosomes

Abstract

Herbosomes have been modified liposomes that can encapsulate botanical extracts and medicinal substances, improving stability, bioavailability, and targeted administration in herbal medicine. A ribosome or similar drug delivery system can improve the absorption rate and amount of drug that cross the lipoidal biofilm, thus overcoming bioavailability issues. Herbosomes, which are herbal drugs based on phospholipids, offer better stability and absorption profiles than other drug delivery systems. Many critical hepatoprotective phytoconstituents, including xanthones, terpenes, and flavones, play roles in effective medication delivery. To achieve therapeutic purposes, such as cardiovascular, antibacterial, dermatological, neurological, anti-inflammatory, chemotherapy for cancer, and health as nutraceuticals, herbosomes can be produced. Twelve characterization procedures and analytical techniques can be adjusted for innovative formulation through particle size evaluation, membrane permeability, percentage entrapped solutes, and drug release. Herbosomes can be used in dentifrices, medicinal gels, and other local delivery methods. In light of rising concerns about medication dependency and safety, and where modern medicine fails to address complex illnesses, people choose traditional treatments with modern technology, such as nano-formulation, for better outcomes with no side effects and a goal to target spot.

1. Introduction

Our country’s rich knowledge base of ayurvedic medicine has recently garnered attention. However, the current approach to delivering herbal medicine to patients is antiquated and traditional, leading to a decrease in drug efficacy. The integration of innovative drug delivery technology into natural medicine is a pivotal concept that can significantly enhance the potency and reduce the adverse effects of various herbs and plants used in natural medicine [1]. Herbosomes have improved pharmacological and pharmacokinetic properties, making them effective for treating acute and chronic liver disorder [2]. Phytomedicines have been used to treat various diseases since ancient times, and different plant materials have been shown to exhibit multiple biological activities, such as immunomodulatory activity, antilipidemic activity, hepatoprotective activity, and others [3]. In vitro, numerous plant extracts display remarkable bioactivity. However, due to their inadequate molecular size and low lipid solubility, the constituents of the plant extract are often poorly absorbed and have low bioavailability. Additionally, when taken orally, gastric fluids can destroy these constituents [2]. This leads to increased bioavailability of herbosomes compared to noncomplex plant extracts. Herbosomes are innovative herbal products that combine phospholipids, resulting in a better absorption and utilization profile in the body. This improves therapeutic efficacy compared to conventional herbal extracts or individual molecules [4]. Herbosomes can help overcome the limitations of traditional therapies [5]. Phospholipids in herbosomes have proven health benefits and demonstrate better pharmacokinetic and pharmacodynamic profiles than conventional herbal extracts [6]. Traditional medicine systems, such as African, Chinese, and Indian systems, usually involve crude extracts of various herbs, which may contain unwanted and sometimes toxic principles and active ingredients [7]. Specific or groups of similar plant ingredients are extracted, isolated, and tested for their therapeutic properties using photo and analytical chemistry methods [8].

2. Herbosomes and liposomes: A comparison

Using appropriate methods, liposomes can be created by combining water-soluble phytoconstituents with phosphatidylcholine in a specific ratio. This process does not involve the formation of chemical bonds; instead, the water-soluble phytoconstituents are held in place by the phosphatidylcholine, resulting in the drug molecule being surrounded by hundreds or even thousands of phosphatidylcholine molecules (Figure 1). Regarding her bosoms, the phosphatidylcholine and plant constituents join together in a 1:1 or 2:1 ratio, and the phagosome process involves the formation of chemical bonds. In contrast, liposomes do not form chemical bonds between the phosphatidylcholine molecule and the phytoconstituents. Pyrosomes are more bioavailable than liposomes since they have a lower phospholipid content and are absorbed more effectively [9].

Figure 1.

Schematic diagram of the liposome and herbosome.

3. Properties of herbosomes

3.1 Physical properties

• Herbosomes are made up of lipophilic compounds that have specific melting points.

• The size of these bosoms usually varies between 50 nm to a few 100 μm.

• When herbosomes come in contact with water, they form liposomal-like structures with a micellar shape [10].

3.2 Chemical properties

• Ribosomes are complexes between the phospholipid’s polar head and the substrate’s water-soluble functional group [11].

• They formed hydrogen bonds between the polar head of the phospholipid and a polar portion of the substrate [12].

• Herbosomes develop micelle-like liposomes when exposed to water [13].

3.3 Genetic properties

• Phytosomes are novel complexes that are highly absorbed and used. Hence, they manufacture additional bioavailability and higher results than the standard natural herb or non-complexed extracts established by pharmacokinetic studies or pharmacodynamic tests in experimental animals and human subjects.

• Phytosomes categorize their behavior in a physical or biological system based on their physical size, membrane porosity, percentage entrapment, chemical composition, and the amount and purity of the materials used [14].

3.4 Physio-chemical properties

• Phytosomes can be produced by reacting to a stoichiometric amount of phospholipid with phytoconstituents in an aprotic solvent.

• The size of phytosomes can range from 50 nm to a few 100 μm.

  When exposed to water, phytosomes take on a micellar shape similar to liposomes, and photon correlation spectroscopy (PCS) can reveal these liposomal structures formed by phytosomes [15].

4. Mechanism

The binding of polyphenolic components in plant extracts directly to phosphatidylcholine has been well-established. When combined with standard extracts or polyphenolic components, such as simple flavonoids, in an aprotic solvent, phospholipids like soy phosphatidylcholine produce herbosomes. Phosphatidylcholine is a bifunctional molecule, comprising a lipophilic phosphatidyl moiety and a hydrophilic choline moiety. These chemicals are primarily bound by the choline head of phosphatidylcholine, and the lipid-soluble phosphatidyl section, consisting of the body and tail, surrounds the choline-binding substance. The outcome is the formation of the phyto-phospholipid complex, a lipid-soluble molecular complex between the phytomolecules and phospholipids. The polar head of phospholipids is where phytomolecules are chemically bonded, as shown by spectroscopic methods. However, according to the chemical study, the herbosome unit usually comprises at least one phosphatidylcholine molecule and one or more flavonoid molecules (Figure 2) [16].

Figure 2.

Mechanism of phytosome complex formation (herbosome).

The fundamental mechanism responsible for the formation of herbosomes, in dependent of the manufacture technique, is the interplay between hydrophobic and hydrophilic lipid-lipid and lipid-water molecules. It has been suggested that symmetric membranes need energy to curve because they desire to be flat (spontaneous curvature: CO = 0). Membrane curvature is determined by several factors, including the kind of lipids utilized and the presence or lack of sterols. Lipid-water systems with a cylindrical shape, which constitute bilayer sheet structures, can take on curves and become liposomes [17].

5. Excellence of herbosomes

1. Enhanced delivery to the target site, systematic absorption, and bioavailability: As herbosomes are likely to pass through the lipophilic environment of cell membranes, enter the cell, and ultimately enter the circulation, they offer a natural way to improve the usage of herbal formulations. The extracts are better absorbed by the intestinal lumens and more effectively penetrate the skin for dermal and transdermal administration. Because of increased bioavailability, a lower phytoconstituent dose is needed to achieve the intended result. There is also an increase in the action’s duration. Herbosomes withstand the activity of gut microorganisms and are more stable in the stomach environment. Additionally, because the complex is biodegradable, drug entrapment is not an issue with herbosomes [18, 19].

2. Safety: The herbosome technique is noninvasive and passive. Herbosome components can be used in cosmetic and medicinal products and are nontoxic and nonmutagenic [20, 21]. Hydrophilic solvent ethanol has now primarily replaced hazardous organic solvents such as tetrahydrofuran and dichloromethane, which are used in conventional procedures to generate herbosome complexes, enhancing their safety and potential for clinical applications.

3. Additional advantages: No complex technological investments are needed, and the production of herbosomes is a relatively straightforward procedure. Since the toxicological profiles of the components of herbosome technology are well-documented in scientific literature, there is little risk associated with developing new drugs [21]. In addition to their physiologically acceptable pharmacokinetic and toxicological profiles, the phospholipids used in creating herbosomes have several important medicinal qualities for humans. Phospholipids, such as phosphatidylserine, which functions as food for brain cells, increase the nutritional value of the plant extract.

4. Phospholipids are an excellent source of choline and phosphatidylcholine, which melt fat deposits in the liver, such as in fatty liver or hepatic steatosis. Research has demonstrated the hepatoprotective properties of soy phospholipids, which work in concert to protect the liver from toxins, alcohol, and other medications. Additionally, they have been shown to raise plasma levels of circulating HDL and help with blood cholesterol clearance [20]. Phospholipids with a particular affinity for biological membranes include phosphatidylcholine. Phosphatidylcholine has been demonstrated to be integrated into the cell membrane in place of cellular phospholipids, altering the membrane’s flexibility and helping to nourish and preserve the skin. Additionally, because herbosomes are poorly soluble in aqueous solutions, the creation of stable emulsions and creams is made possible by the limited solubility of herbosomes in aqueous environments.

5. Drug delivery platform for numerous drug groups such as peptides and molecular proteins [22].

6. Phytoconstituent dose is lowered due to enhanced bioavailability of plant-based constituents in complex form [23].

7. The herbosomes formulation looks at strengthened phytoconstituent permeability across biological membranes. It is simple to formulate as there is no specific issue in drug entrapment.

8. They increase bioavailability and systematic absorption and ensure distribution to the target site. They can be carried across lipophilic cell membrane environments and improve extract absorption in the intestinal lumen and permeation through the skin for dermal and transdermal application [22].

9. Phytoconstituents generate a small cell that protects the critical components of herbal extracts from deterioration by gut bacteria and digestive secretions [24].

10. The dosage needed is lowered because the significant ingredient enhances absorption. They can also contribute smaller amounts to attain the desired outcomes [25].

11. The vesicular system is apathetic, non-intrusive, and ready for commercialization immediately [26].

12. The dosage needed is lowered because of enhanced absorption of the primary ingredient. They can also contribute smaller amounts to attain the desired outcomes [27].

6. Failing of herbosomes

1. Complicated manufacturing process: The intricate manufacturing procedure needed to create herbosomes is one of their disadvantages. In this procedure, active plant components are extracted and then bound to phospholipids. The several steps in this process might make production more expensive and make it more difficult to scale up production for commercial usage.

2. Leaching of the phytoconstituents off the “some,” which lowers the intended medication concentration and suggests their unstable nature, maybe the chief drawback of herbosome [28].

3. Plant constituents in herbosomes are rapidly removed and have a short half-life [27].

4. Because of their increased size, complications will arise while attempting to focus on the various tissues [23].

5. There is a high cost of manufacture and a typical predominance of aversions to ribosomal components.

7. Application

• Herbosomes are also used as an anti-inflammatory, lipolytic, isokinetic, anti-edema, cicatrizing, trophodermic, nutraceutical immunomodulator, antioxidant for skin and liver, cardioprotective, anti-wrinkle, and UV protectant [7].

• Grape seed, for example, is employed as an antineoplastic and inhibitor. It is used to treat benign prostatic dysplasia and as a cancer chemopreventive medication.

• A phytosome in grape seeds comprises phospholipid-complexed oligomeric polyphenols with different molecular sizes. Procyanidin flavonoids from grape seeds have several key characteristics, including a significant protective effect against atherosclerosis, a boost to the human body’s natural antioxidant defenses, an increase in total antioxidant capacity, and protection against heart damage caused by ischemia and reperfusion. These actions are achieved through complicated mechanisms that go beyond the flavonoids’ higher antioxidant potency [29].

• Green tea’s long-term health benefits include its antioxidant, antimutagenic, anticarcinogenic, antiatherosclerotic, hypocholesterolemic, cardioprotective, and antibacterial properties. Green tea polyphenols have very low oral bioavailability from standard preparations, notwithstanding their potential activity. Their combination with phospholipids significantly improves their low oral bioavailability [30].

• By preserving glutathione in the parenchyma cells, silybin shields the liver, while parenchyma cells (PC) aid in cell membrane replacement and repair. These ingredients probably have the combinatorial effect of protecting liver cells from oxidative damage [31].

• They are used to treat hyperlipidemia and vascular and skin problems.

• They are also used to treat high blood pressure.

• It aids in treating heavy metal toxicity through chelation therapy.

• Useful for safe gene therapy.

• Any fundamental nano-formulation must have a specific target, site avoidance administration, and intracellular drug delivery [32].

8. Characterization and evaluation

8.1 Characterization

8.1.1 Visualization

Transmission electron microscopy (TEM) can visualize herbosomes, revealing their internal composition and characteristics, such as morphology, crystallization, stress, and magnetic domains [7].

8.1.2 Vesicle size and zeta potential

Vesicle size and shape over time can be used to evaluate vesicle stability. Dynamic light scattering (DLS) measures size and TEM monitors structural changes [4]. Zeta potential for herbosomes may also be measured using a computerized inspection system and photon correlation spectroscopy (PCS).

8.1.3 Entrapment efficiency

The ultracentrifugation technique may assess the entrapment efficiency of herbal medicine formulations using herbosomes. Liposomes were centrifuged at 2000 rpm for 1 hour at a regulated temperature of 4°C. The supernatant containing unentrapped medication was removed, and UV spectrophotometrically evaluated against phosphate-buffered saline pH 7.4 [32].

8.1.4 Transition temperature

Differential scanning calorimetry may be used to assess the transition temperature of vesicular lipid systems [4].

8.1.5 Surface tension activity measurement

Using a Du Nouy ring tensiometer and the ring technique, it is possible to determine the surface tension activity of medication in an aqueous solution [23].

8.1.6 Stability studies

The capacity of vesicles to hold the medication was determined by maintaining liposomal solutions at 4–8°C for 60 days. The physical examination, drug content, and particle size distribution investigations for liposomal suspension were conducted regularly [32].

8.1.7 Drug content

Quantifying the quantity of medication can be done using a modified high-performance liquid chromatographic (HPLC) method or an appropriate spectroscopic approach [23].

8.2 Spectroscopic evaluation

8.2.1 In vitro and In vivo evaluation

The selection of in vitro and in vivo assessment models is based on the potential therapeutic effectiveness of physiologically active phytoconstituents present in herbosomes. For instance, the compound’s stability can be evaluated by comparing its emission spectrum at different time points in the solid state with a spectrum of a dispersion in water made up of small particles. To assess the stability of phytosomal gels of meconazole, an optimized gel formulation of meconazole was kept at 40 and 4°C for 90 days and then examined for pH, thickness, and drug content modification. The in vitro anti-hepatotoxic activity is often determined by evaluating the ribosomes’ antioxidant and free radical scavenging activity [33].

8.2.1.1 In vitro drug release

Investigating different pH levels using commonly available dissolving equipment is in vitro drug release. The outcomes are evaluated based on the active ingredients therapeutic action [27].

8.2.1.2 In vitro permeation study

For an ex vivo permeation investigation of the phytosome compound gel of legal substance measuring 1.5 cm², an improved Franz diffusion cell with a capacity of 7 ml was utilized. To ensure accuracy, a literature review was conducted and a diffusion medium of phosphate buffer saline pH 7.4 was employed. The dermal surface of rat skin/cellulose acetate membrane measuring 0.5 cm² was treated with a phytosome compound gel containing a legal substance and a plant drug gel. A needle-shaped magnetic stirrer was used to continuously mix the diffusion medium at a rate of around 300–350 revolutions per minute (rpm). The use of hot water helped to keep the temperature at 32 ± 0.5°C. For 6 hours, the diffusion was passed. The 0.5 ml sample was removed at predetermined intervals (0.5, 1, 2, 4, and 6 hours) and replaced with an equivalent volume of freshly made phosphate buffer saline with a pH of 7.4. The solutions’ absorbance was determined at 227 nm using UV spectrophotometry. How much medicine permeated the phytosome compound gel of lawsone and the plant drug gel was determined cumulatively [13].

8.2.1.3 In vivo anti-inflammatory study

Four male Wistar rats formed teams for management, inflammation, phytosome gel, and plant medication gel. Every rat was given regular food and kept on a 12-hour light/dark cycle. Furthermore, rats became used to the daily anti-inflammatory activities for a week. Rats were given 0.2 ml injections of a substance known as (1% w/v) under their right and left paw’s planter regions to cause inflammation. The present-day 01 orchid scientifics, India digital paleothermometer, was used to measure the anti-inflammatory activity [34].

8.2.2 H-NMR

In polar solvents, a modification is noticeable in the 1H-NMR signal of (+)-catechin and its stoichiometric complex with distearoylphosphatidylcholine. This alteration is due to the atoms that participate in the formation of the complex and is not the outcome of any aggregation of the signal characteristic of the individual molecules. It is necessary to broaden the signals from the flavonoid’s protons to prevent the proton’s discharge. In the case of phospholipids, all signals become broader, while the singlet corresponding to N-(CH3)3OF choline shifts higher. When the sample is heated to 60°C, extra broad bands appear, primarily related to the resonance of the flavonoid moiety [23].

8.2.3 C-NMR

The carbons of the phytoconstituents were not visible when recording the C-NMR of both the phytoconstituents and the stoichiometric compound with phosphatidylcholine. However, the signals associated with the glycerol and choline portions were amplified and shifted some [7]. Nuclear resonance study of umbelliferone H-NMR. The samples of umbelliferone and composition were dissolved within the solvent dimethyl sulphoxide and analyzed with a Bruker Avance II 400 NMR spectroscope. The spectrum was obtained and compared for the drug and composition. The 13C-NMR spectrum was taken to confirm the interaction between the drug and lipoid and, therefore, the formation of the composition. The sample of umbelliferone and composition was dissolved within the solvent dimethyl sulphoxide and then analyzed with a Bruker Avance II 400 NMR spectroscope (SAIF, Panjab University, Chandigarh). The spectrum was obtained and compared for the drug and complex [35].

8.2.4 FTIR

Comparing the spectrum of the complex and the individual components to that of the mechanical mixes can be done using FTIR to support the spectroscopic evaluation of the produced complex. Determining the stability of the ribosomal complex can also be achieved through FTIR, which is a valuable tool. To validate the strength of the complex in solid form, the spectra of the complex in solid form can be compared with the spectrum of micro-dispersion in water after lyophilization at various intervals, which is a practical approach [4]. In a laboratory setting, the stability will be verified by comparing the spectrum of the compound in the solid form (herbosomes) with the spectrum of its micro-dispersion in water after lyophilization, at entirely different times. For basic formulations, the spectrum of the excipients (blank) must be subtracted from the spectrum of the cosmetic type at entirely different times, and the remaining spectrum of the compound itself must be compared [27].

The meconazole phytosome FTIR spectrum analysis indicates any interactions between the various functional groups present in the drug and excipients. This study used the FTIR peak matching technique to assess the compatibility between the drug, SRE, lipid, and alternative excipients. The FTIR spectra of meconazole, SRE, and MP1B were compared several times. All of the characteristic peaks of MCZ and SRE of C-Cl, C=C, C-O, C-N, -O H, and C=O were maintained within the formulation and were detected multiple times at 638.46 cm⁻¹, 1612.54 cm⁻¹, 1089.82 cm⁻¹, 1375.58 cm⁻¹, 3400 cm⁻¹, and 1734.06 cm⁻¹, respectively. No physicochemical interaction between MCZ, SRE, and Soya lecithin was found, and MCZ and SRE were present within the pure type within the formulation [36].

8.2.5 DSC differential scanning measuring

DSC may be a rapid and dependable tool for analyzing the interaction of various components and medication excipient compatibility. The absence of an endothermic peak characterizes these interactions, the appearance of the most recent peak, changes in peak shape, onset temperature, relative peak space, or total heat. The sample was weighed (2.00–10.00 ± 5 mg) and put into a sealed aluminum crimp cell. The sample was scanned in a N2 environment at 100°C per minute up to 3500°C. Temperatures at which peak transitions begin were noted [27].

DSC can be utilized to accurately and promptly investigate phytosome drug excipient compatibility and multiple element interaction in citrus lemon. The presence of these interactions can be detected by observing the disappearance of the endothermic peak, appearance of the most recent peak, change in the peak form, onset temperature/melting point, relative peak area, or enthalpy [37].

8.2.6 Zeta potential

Zeta potential was assessed using a Horiba SZ 100Z particle size instrument with the zeta potential measurement mode. The lead to a zeta potential of 25 mV confirms the advance’s stability. (Sahu D, Pratap R, Rajput S, Patel L, Dewangan P. An updated review on formulation, characterization, and evaluation of herbal and synthetic liposome Vol. 9, International Journal of Creative Research Thoughts. 2021. Available from: www.ijcrt.org). For example, samples were separated into water and placed under 15 minutes of sonication. Before testing, the samples were diluted with water (1:10). Meconazole’s zeta potential in the phytosomes zeta potential was calculated using the zeta potential measuring mode on a Horiba SZ 100Z particle size analyzer. The compound’s stability is indicated by the resulting zeta potential of 25 mV [36].

9. Novel targeted drug delivery systems

Novel targeted drug delivery systems are a type of medication delivery strategy that differs from traditional drug delivery methods. In the case of herbosomes, it is important to note that the effectiveness of herbal therapy depends on delivering the right amount of therapeutically active components. The negative impact of specific plant components can be minimized with this approach. Traditional herbal remedies were not commonly used in modern formulations due to their fast effects, lack of scientific explanation, and difficulties in processing, such as standardization, extraction, identification of specific components, and blending with other excipients. However, current phytopharmaceutical research has addressed scientific requirements such as pharmacokinetics, mechanism of action, site of action, precise dose forms, additional binding agents, and more. This has led to the incorporation of herbal remedies into novel targeted drug delivery systems, which can be broadly classified [24].

Vesicular delivery systems:

1. Liposomes

2. Ethosomes

3. Transferosomes

Particulate delivery systems:

1. Microsphere

2. Nanoparticle

3. Micro pellets

Biphasic delivery systems:

1. Micro/Nanoemulsion

9.1 Vesicular delivery systems

• Vesicular drug delivery systems are highly organized assemblies composed of one or more circumferential bilayers created due to amphiphilic building blocks self-assembling in the presence of water. They are essential for the targeted administration of medicines because of their capacity to localize drug activity at the site or organ of action, minimizing its concentration at various locations in the body [37].

9.1.1 Liposomes

• Liposomes are colloidal, concentric bilayered vesicles in which the aqueous compartment is surrounded by a bilayer membrane consisting primarily of natural or synthesized lipids. Phospholipids are critical liposomal drug delivery system components, while cholesterol is a fluidity buffer. Liposomes have become popular medication carriers for targeted drug delivery [38].

9.1.2 Ethosomes

• Ethosomes are lipid, soft, pliable vesicles comprised of phospholipid, ethanol, and water that act as a permeability modifier. They have the impact of enhanced cell membrane lipid fluidity induced by Ethosomes’ ethanol, which results in increased skin permeability, while this is focused on the deep skin layer [39].

9.1.3 Transfersomes

• Transfersomes are organisms that transport bodies. It is a highly deformable, stress-sensitive complex vesicle with an aqueous core surrounded by a tough bilayer of lipids. These synthetic vesicles are made up of one natural amphiphilic lipid and a bilayer softener, which is a biocompatible surfactant. Amphiphilic surfactants allow transferosomes to reversibly adjust their membrane composition to pass through tiny skin pores (Table 1) [40].

Vascular system	Description	Applications
Aquasomes	Aquasomes have water-like properties with a diameter from 30 to 500 nm. They are nanoparticulate carrier systems with a three-layered self-assembled structure. The particle core is composed of nanocrystalline calcium phosphate coated with a polyhydroxy oligomeric film.	Specific targeting, molecular shielding, carrier for delivering vaccine, hemoglobin, drugs, dyes, and enzymes.
Archaesomes	Archaeosomes, which possess potent adjuvant activity, were obtained from archaebacteria that are capable of producing methane. The vesicles are made up of glycerolipids that belong to the archive and exhibit strong adjuvant activity.	It is used in delivering cancer antigens in combination with checkpoint inhibitor immunotherapies. Poor adjuvant activity.
Colloidosomes	A new type of microcapsules called colloidosomes have been developed. These microcapsules have shells that are made up of coagulated or fused colloid particles located at the interface of emulsion droplets. Colloidosomes are hollow shells that have controllable permeability and elasticity.	Use in drug targeting.
Cryptosomes	The topmost stratum of phosphatidylcholine is a preferred polyoxyethylene derivative originating from phosphatidyl ethanolamine.	Use in drug targeting and ligand-mediated drug delivery.
Carbohydrase	Multidimensional structures are created using carbohydrate-based lipids that can be zwitterionic, cationic, or anionic in nature in this new formulation.	Use in drug targeting.
Cubosomes	The bi-continuous cubic phases are made up of two hydrophilic regions that are separate and continuous. These regions are not intersecting, and they are divided by a lipid layer.	Use in drug targeting.
Escheriosomes	Lipid vesicles made from polar lipids extracted from Escherichia coli.	Use in drug targeting.
Genomes	A functional gene transfer can be facilitated through the use of a synthetic macromolecular complex.	Cell-specific gene transfer.
Layersome	The layersomes consist of several layers and are coated with biocompatible polyelectrolytes to reinforce their structure.	Oral administration and incorporation in biomaterials
Pharmacosomes	Pharmacosomes consist of drugs and lipids that form an amphiphilic structure. The drugs are conjugated to lipids with the help of hydrogen bonds. Pharmacosomes can exist in the form of ultrafine vesicular, micellar, or hexagonal aggregates.	Improving the solubility and bioavailability of various drugs while reducing their gastrointestinal toxicity can be achieved through the delivery of hydrophilic and lipophilic drugs.
Transfersomes	Ultra-deformable and self-optimized aggregates called transfersomes are utilized for transdermal application. These aggregates contain lipids and membrane softeners that are biocompatible.	Use in drug targeting.

Table 1.

Vesicular systems and their applications.

9.2 Particulate delivery systems

The most modern treatments include medications made up of micro-nanosized particles (particulate DDS) that can diffuse into the circulation and be carried into arteries, veins, and capillaries while crossing barriers, preventing big particles and organisms from exiting the system. The cardiovascular system uses two mass transport mechanisms to transmit drug particles: advection and diffusion. As a consequence of advection, the medication particles are translated while in suspension of the blood, which flows at varying speeds in different parts of the cardiovascular system. As a result of diffusion, drug particles diffuse in the circulation from a high-concentration zone to a low-concentration region via Brownian motion. This is explained by particle diffusion rules, namely the diffusion–advection equation.

9.2.1 Microsphere

Microspheres are tiny, spherical particles with a 1–1000 nm size range. These particles comprise a polymer matrix that uniformly contains medicine and are released using first-order kinetics. Microspheres can be manufactured from natural or synthetic polymers. Due to their high surface-to-volume ratio, microspheres and micro pellets are commonly used for sustained drug delivery. For this purpose, gastroretentive floating microspheres of silymarin are particularly effective.

9.2.2 Nanoparticle

Nanoparticles are submicron-sized particles with a diameter of around 200 nm composed of biodegradable and nonbiodegradable polymers. They enhance component solubility, better absorb integrated medication, and reduce dosage and dose-related adverse effects. They are chiefly used for controlled release and medication targeting particle tissue and organs.

9.2.3 Micro pellets

• Micro pellets are tiny solid particles ranging from 1 to 1000 nm. The medicine contained within these micro pellets can be dissolved or scattered in polymeric solutions using a method known as spray drying. This quick-drying approach is a one-step process and can be easily scaled up, making it ideal for use with heat-sensitive pharmaceuticals. Researchers have discovered that micro pellets made from alginate-based andrographolide derived from Andrographis paniculate can release medication away from the upper gastrointestinal tract. This can help prevent GIT irritation and related issues such as nausea, loss of appetite, and vomiting [41].

9.3 Biphasic delivery systems

Biphasic vesicles are a novel lipid-based delivery technology that combines the benefits of liposomes and emulsions. Concentric phospholipid bilayers enclose aqueous, oil, and micellar compartments in these vesicles. Structural investigations demonstrate a specific scattering characteristic distinguishing biphasic vesicles from simple liposome-emulsion mixes. These cysts have an average diameter from 1 to 10 m, with submicron emulsion droplets at 300 nm and micellar compartments at 50 nm. A phospholipid phase (soya phosphatidylcholine, cholesterol, monolauroyl lysine, and propylene glycol) and a submicron emulsion phase (vegetable oil, surfactant, fatty alcohol, glycerol ester, and wax) comprise the composition. Biphasic vesicles can be customized for drug delivery, including permeability enhancers for transdermal or more profound tissue drug administration.

9.3.1 Micro/nanoemulsion

The o/w type emulsions are micro and nanoemulsions, with sizes ranging from a few nanometers to a few microns. It is a surfactant-stabilized thermodynamically stable dispersion of two immiscible liquids. High-pressure homogenization and microfluidization procedures are used to prepare them. Many herbal medicines and phytoconstituents are mixed into microemulsions for various uses [41].

10. Current strategy of herbal drug formulation

Charles K Armes established phyto technologies, advanced aromatherapy, and herbal medicine. The company produces concentrated liquid phytopharmaceutical extractions from plants and incorporates phytochemical components into body care products. Herbo technologies markets its products directly to consumers and natural practitioners through the Internet. The company also sells some of its products, such as the hair coloring line and the nasal spray, through drug stores and other mass outlets. Furthermore, customers can purchase products online from health food stores and other outlets.

11. Benefits of herbal formulations

1. Some substances can have a higher bioavailability.

2. The delivery of substances to various biological tissues is pharmacologically ensured.

3. Nutrient safety is not compromised.

4. A reduced dosage of the main ingredient can be used due to increased absorption.

5. The drug loading efficiency is predetermined and high because of drug and lipid conjugation, forming cysts.

6. There is no issue with drug entrapment.

7. Herbosomes are superior to liposomes in skin care products.

8. The unique structure of herbosomes has advantages in cosmetic applications.

9. Herbosomes can cross cell membranes and enter cells more efficiently.

12. Future aspects

Herbosomes offer several features that make them appealing as medication carriers for topically administered medicines. They differ in size and surface features, and they can operate as sustained release depots, releasing encapsulated medicines with half lifetimes ranging from 0.6 to 11 days. Furthermore, because of their collagen surface features, a new generation of liposomes known as “collagen-modified Herbosomes” can modulate the herbosomes’ and herbosomes’ cell contact. Topically applied ribosomal formulations, particularly those made from lipid mixes comparable to the stratum corneum’s composition, might be an effective delivery strategy for treating skin problems. In the future, herbosomes will be created for medication delivery with little toxicity and maximum efficacy.