Advances in Phytosomes as a Targeted Drug Delivery System for Herbal Medicines

Abstract

Novel drug delivery systems (NDDS) have gained significant attention for improving the bioavailability and therapeutic efficacy of drugs, especially those derived from herbal sources. Among various vesicular systems, phytosomes have emerged as a promising technology for enhancing the absorption of poorly bioavailable phytoconstituents. Phytosomes are lipid-based complexes formed by the interaction of plant extracts with phospholipids, primarily phosphatidylcholine, resulting in improved membrane permeability and stability. This system facilitates the transition of hydrophilic plant constituents into lipid environments, thereby enhancing their absorption and systemic availability.Phytosomes offer several advantages, including improved pharmacokinetic profiles, better stability, and enhanced therapeutic effectiveness compared to conventional herbal formulations. Various preparation methods such as solvent evaporation, mechanical dispersion, and salting-out techniques are employed for their formulation. Additionally, characterization techniques like DSC, SEM, TEM, FTIR, and zeta potential analysis are used to evaluate their physicochemical properties. Despite certain limitations, phytosomes represent a significant advancement in the field of herbal drug delivery, with promising applications in pharmaceutical and nutraceutical industries.

Keywords

Phytosomes, Novel Drug Delivery System (NDDS), Bioavailability, Phospholipids, Herbal Drug Delivery, Vesicular Systems, Pharmacokinetics, Phytoconstituents, Lipid-based Drug Delivery, Targeted Drug Delivery

Introduction

Novel drug delivery techniques can increase bioavailability. The goal of novel drug delivery system is to route the active ingredients to the site of action while delivering the medicine at a rate determined by the body’s needs during the treatment period. A number of novel vesicular drug delivery system such as liposomes, niosomes , transferosome  and pharmacosomes have been emerged for controlled and targeted drug delivery.¹  The phytosomes technology, an a novel drug delivery system, produces a little cell better able to transit from a hydrophilic environment into the lipid friendly environment of the enterocyte cell membrane and  from there into the cell.² Many methods have been discovered to increase the oral bioavailability of drugs, including structural modification the addition of solubility and bioavailability enhancers.¹The term “ phyto” denotes plant origin while “some” implies a cell –like structure phytosomes , also known as herbosomes, are vesicular drug delivery system designed to improve the absorption and bioavailability of poorly soluble compounds.³ this in a new patented technology, where standardized plant extracts or water soluble phytocnstituents are complexed with phospholipids to produce lipid compatible molecular complexes there by greatly increasing absorption and bioavailability.⁴ Phytosomes means herbal drug loaded in vesicles , which is available in the Nano form. The phytosomoes provide an envelope like coating around the active constituent of drugs and due to this chief constituents of herbal extract remains safe degradation by digestive secretion and bacteria phytosomes its effectively able to absorb be from a water loving environment into lipid loving environments of the lipids loving environments of the cell membrane and finally reaching to blood circulation. The current review highlights the future scope and emerging technologies in the field of NDDS for the benefit of the herbal and traditional medicines prepared from plant origins.⁵

PREPARATION OF PHYTOSOMES

Phytosomes are generally prepared by adding accurate amount of phospholipid i.e soya lecithin with herbal extracts in an aprotic solvent soya lecithin contain main constituents i.e. phosphatidylcholine which is having a dual function. Phosphatidyl part is lipophilic in nature and choline part attached is hydrophilic in nature. The choline part attached with hydrophilic chief active constituents, whereas phosphatidyl part lipid soluble compound attached with choline of lipid complex with better stability and bioavailability.⁶

PROPERTIES OF PHYTOSOMES

Biological properties:

1. When taken orally, Phytosomes improves the overall bioavailability of active substance as well as their active absorption.
2. Phytosomes has a superior pharmacokinetic profile than conventional herbal medicines.
3. These herbal remedies are more innovative than conventional herbal extracts and more effective.

Physicochemical properties:

1. When exposed to water, phytosomes adopts a micellar shape resembling a liposomes and photon correlation spectroscopy (PCS) demonstrate that phytosomes acquired these liposomal structures.
2. Phytosomes ranges in size from 50 nm to a few hundred meters.
3. Using data from the H1 NMR and C13NMR, it was determined that the fatty chain emits the same signals in both free and complex phospholipids. This shows that the active ingredients are encased in lengthy dliphatic chains, creating a lipophilic envelope.

ADVANTAGES:¹

1. Phytosomes have better stability due to strong chemical bonding with lipid.
2. Phytosomes increases cutaneous absorption due to lipid coating.
3. Platform for the delivery of large and diverse group of drugs (peptide, protein molecules),
4. The vesicular system is passive and non-invasive.

 DISADVANTAGES:

1. Stability problem.
2. Phytoconstituents from phytosomes are rapidly eliminated.
3. When administrated orally and topically limit their bioavailability.

METHOD OF PREPARATION OF PHYTOSOMES:

1. Solvents evaporation method
2. Mechanical dispersion method
3. Salting out technique

Solvents evaporation method

The solvent evaporation methods involve integration of the phytoconsitituents and PC during a flask containing organic solvent. This reaction mixture is kept organic solvent. This reaction mixture is kept at an optimum temperature usually 40 ⁰ C for specific interval of 1 hrs to achieve maximum drug entrapment within the phytosomes formed thin film Phytosomes are separated by 100 mesh sieves and stored and desiccators for overnight.⁷ 

Mechanical dispersion method

In the experiment the lipids dissolved in organic solvent are brought be in contact with aqueous phase containing the drug. The next removal of the organic solvent under reduced pressure result in the formation of phyto-phospholid complex. Recently methods for the phospholipids involute preparation includes super critical fluids (SCF), which include gas anti-solvent techniques compressed anti solvent process technique compressed anti solvents process (PCA) supercritical anti solvent method (SAS).⁷

Salting Out Technique:

An important method of phytosomes preparation that done by dissolving both PC& therefore the plant extract during a suitable organic solvent then n-hexane was added unit the extract –PC complex precipitation occurs.⁷

Differential scanning calorimetry:

Drug polyphenolic extract, phosphatidylcholine, a physical mixture of drug extract and phosphatidylcholine, and drug –phospholipid complex placed in an aluminium cell and heated to temperature of 50-250⁰ c/ min from 0 to 400 ⁰c in the atmosphere of nitrogen.

Scanning electron microscopy:

SEM was used to determine the size of the particle and its appearance. Dry sample was placed on electron microscope brass stub coated with gold in an ion sputter. Random scanning of the complex at 100.

Transition electron microscopy

TEM was used to characterize the size of phytosomal vesicles with 1000 magnification.

Drug entrapment and loading capacity:

Drug phytosomes complex was centrifuged at 10000 rpm for 90 minutes at 4 ⁰ c to separate phytosome from the untrapped drug. The concentration of free drug can be measured by doing ultraviolet spectroscopy. The percentage drug entrapment can be calculated as given formula.

Weight of total drug – entrapment efficiency %=weight of free drug weight of total drug ×100

 

Fourier transform infrared spectroscopy:

FTIR analysis done for checking the structure as well as chemical stability of drug. The phytosomal drug will be crushed with potassium bromide to obtain pellets at 600 kg/cm² pressure. Scanning will be done –between the ranges of 4000-400 cm^-1.

Size analysis and zeta potential:

Malvern zeataiszer is used to check the particle size and zeta size of phytosomal complex. Argon laser is used for this particle size and zeta sizer characterization.

In vitro and in vivo evaluation:

In vitro and in vivo evaluation depends on the properties of the drug, chief phytoconstituents bounded by phospholipid layer and on the bases of that particular animal model is selected for its evaluation.

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