An Overview of Phyto-Phospholipid Carriers as Novel Drug Delivery System for Herbal Medicine

In both conventional and contemporary healthcare systems, herbal medicine has a long history. Bioactive substances found in many plants, such as flavonoids and glycosides, offer enormous therapeutic promise in the medical field. But the bioactive because of their hydrophilic character, chemicals frequently have trouble being absorbed, which reduces their bioavailability. Since it directly affects the effectiveness of therapies using herbal products, dealing with this problem has turned into crucial in the profession. Despite the fact that conventional herbal remedies have made major contributions to healthcare, modern advancements in drug delivery systems have prompted the evolution of several cutting-edge methods to boost the bioavailability of herbal compounds. This involves developments in medication delivery technologies that is capable of delivering active substances to certain locations with accuracy and stability .¹

The term “Phyto” means plant while “some” means cell-like structure .² After using many techniques like solubility and bioavailability enhancers which couldn’t met the requirement, the “phytosome technology” was invented by Indena in 1989.³    

Figure 1. Major difference between liposome and phytosome

Because of their improved ability to pass through lipid – rich bio membranes and eventually reach the blood, phytosomes are more accessible than basic herbal extracts. Phytosomes are more adept in moving from a hydrophilic environment into the enterocyte cell membrane’s lipid- friendly environment, then into the cell and ultimately into the blood.⁴ Due to their affinity for the water phase, certain hydrophilic flavonoids have poor absorption rates. Permeability through lipid-rich biological membranes is restricted by poor lipid solubility. Furthermore, flavonoids are big molecules with many phenolic rings that restrict absorption through straightforward diffusion. Water-soluble flavonoids can be transformed into lipid-compatible phytosomes, which are nanoscale molecular complexes. The bioavailability of flavonoids can be increased by using this nanoparticle technique. The membrane barriers were effectively traversed by the nanoparticles.⁵

PHYTO – PHOSPHOLIPID COMPLEX

Complexes consisting of two hydrophobic hydrocarbon chains and a hydrophilic head group are made using phospholipids.⁶ For improved pharmacological relevance, phospholipid is a crucial component in the creation of phytolipid complexes, herbosomes, or phytosomes. The role of phospholipids in the enhancement of drug solubility in the lumen, which modifies the GIT's biochemical and physical barrier function.⁷ Therefore, phytocomplex is a potential approach for natural medications with low bioavailability that are either poorly absorbed due to their large molecular size or because they are not lipid-soluble enough to traverse lipid-rich biological membranes. In order to create lipid-compatible molecules, a standardized plant extract is added to phospholipids during the phytosome manufacturing process. With this method, a herbal medication may more easily go from a substance that is hydrophilic environment into the lipid-friendly membrane of an enterocyte cell environment, then into the cell and ultimately into the blood.⁸

Figure 2. Phytosome molecular complex

Figure 3. Benfits of phyto- phospholipid complexation⁹

MERITS OF PHYTOSOMES:

1. Improved drug penetration into the skin, and since it is lipoidal, the drug that penetrates the skin concentrates there and stays there for a longer amount of time, making it possible to target the skin with medication.¹⁰
2. The Phyto-phospholipid complex is a potentially effective medication delivery method for enhancing oral absorption and bioavailability in herbal medication.¹⁰
3. There is no problem with drug entrapment since the medication creates vesicles in conjunction with lipids, resulting in an elevated and more than specified entrapment efficiency.¹¹
4. Although a lower dosage was needed, it had a positive therapeutic impact.⁶
5. They are beneficial in the treatment of acute illnesses besides pharmaceutical and cosmetic formulations due to their enhanced pharmacokinetic and pharmacological properties.¹²
6. In addition to serving as a carrier, phosphatidylcholine is a substance that necessary component of cell membranes, provides nourishment to the skin throughout the plantersome process.¹¹
7. In humans and other higher animals, phospholipids are also utilized as natural digestive aids and transporters of water and fat-soluble substances.¹³
8. Phosphatidylcholine improves a range of liver ailments by functioning as a liver-protectant in addition to being a carrier.⁸
9. Chemical connections are created between phosphatidylcholine molecule and phyto-constituents, so the Phytosome displays improved stability.⁸
10. They have synergistic impact for flavonoids.³
11. They themselves have hepatoprotective action.³
12. Their commercial scale production is easy.³

PHYTOSOMES AND LIPOSOMES DIFFERENCE

Table 1. Additional benefits of phosolipid complex

SOLVENT

The phospholipid's solvent selection complexation procedure is founded on how soluble the medication and phospholipids are. Actually, research recommends using both protic and aprotic solvents, and numerous Research has even shown that using a combination of solvents improves solubility. Recently, ethanol—which is safer than the previous ones—replaced the majority of aprotic solvents, including diethyl ether, dichloromethane, dioxane, chloroform, and n-hexane. The diverse solvents utilized by various studies.¹⁹

Table 2. Works on phytosome, method used, solvents used

Figure : Common stage for preparation of phytosome^12,20

Method of preparation phyto-phospholipid complex

SOLVENT EVAPORATION METHOD^[21]

ANTISOLENT PRECIPITATION METHOD/ SALTING OUT METHOD^[22]

ROTARY EVAPORATION TECHNIQUE^[23]

CHARACTERIZATION OF PHYTO-PHOSOPHOLIPID COMPLEX

Solubility and partition coefficient

The n-octanol/water partition coefficient (P) and solubility in water or organic solvents are required to define active ingredients, active constituent phytophospholipid complexes, and physical combinations. The lipophilicity of phyto-phospholipid complexes is often better than that of their active ingredients and also, they are typically more hydrophilic.^[6]

Vesicle size, polydispersity index and zeta potential

Vesicle size, zeta potential, and polydispersity index (PDI) are crucial characteristics of phytosomes that are linked to their dependability and stability. High zeta potential phytosomes demonstrate a high degree of electrostatic repulsion between their constituent particles, a sign of increased stability. The phospholipid complexes' mean size often falls within the 50 nm to 100 µm range. Using dynamic light scattering and a particle size analyzer, the particle size, polydispersity index, and zeta potential are determined.^[24]

The entrapment efficiency (%)

Using a Spectrophotometry UV-Vis technique, the entrapment effectiveness (%) of the variable concentration between leaf extract and phospholipid (1:1:1:2:1:3) was determined. In the centrifuge tube, 1 milliliter of the phytophospholipid complex suspension was placed. A total of 10 milliliters of water was included into the solution. A centrifuge was used to separate the mixture for one hour at 14,000 rpm. Using a spectrophotometer UV-Vis, the total phenolic content of 1 milliliter of supernatant was determined. The wavelength used to calculate the absorbance was 753 nm. Three duplicates of each sample were measured.^[25]

The calculation of entrapment efficiency[%] followed the equation:

ENTRAPMENT EFFICIENCY[%]  = T – S X 100

                                                   T

Where,

T= Total solvent content present in the phyto-phospholipid complex taken

S= Total phenolic content present in the supernatant

T – S=Total solvent content entrapped in phyto-phospholipid complex ^[25]

Scanning electron microscopy (SEM) and transmission electron microscopy (TEM)

SEM has produced important new data on the surface appearance and solid-state characteristics of complexes. TEM is frequently used to investigate the dispersion and crystallization of both to quantify the size of nanoparticles and nanomaterials. According to SEM, active chemicals may be seen in a highly crystalline condition, however following complexation, the structured crystals vanished. Using TEM, it was demonstrated that phyto-phospholipid complexes display vesicle-like structures when diluted in distilled water with mild shaking.^[26]

Organoleptic assessment

Herbosomes' organoleptic properties are identified by their color, scent, and transparency. The drug's wavelength maxima are also determined by both soluble and organoleptic analysis.^[27]

Fourier Transform Infrared spectroscopy (FTIR) analysis

FTIR has conducted investigations on the interactions between herbal medications and excipients. Soy lecithin, their physical mixing, lyophilized powders of their ideal combination ratios, and phosholipid-herbal complex were examined. FTIR (PerkinElmer FT-IR Spectrometer) was used to analyze the samples following their combination with dry crystalline KBr powder in a 1:100 ratio. The scanning range was 4000-400 cm-1, and the resolution was 1 cm-1.^[28]

Drug content (g)

The amount of medicine can be measured using a suitable spectroscopic approach or a customized HPLC.^[29]

Table 3. Commercial preparations of phytosomal herbs