Transferosome: A Vesicular Transdermal Delivery System for Enhanced Drug Permeation

 

Snehal Arjun Kurhe, Kedar Bavaskar, Ashish Jain

1Student, Department of Pharmaceutics, Shri. D.D. Vispute College of Pharmacy and Research Center, Panvel.

2Assistant Professor, Department of Pharmaceutics, Shri. D.D. Vispute College of Pharmacy and Research Center, Panvel.

3Principal, Department of Pharmacy, Shri. D.D. Vispute College of Pharmacy and Research Center, Panvel.

*Corresponding Author E-mail: snehal.kurhe2898@gmail.com

 

ABSTRACT:

The barrier function of the skin limits transdermal medication delivery. Vesicular systems are one of the most contentious mechanisms for delivering active compounds transdermally. The discovery of elastic vesicles such transferosomes, ethosomes, cubosomes, phytosomes, and others reignited interest in creating transdermal delivery systems. Vesicular drug delivery systems are highly organised assemblies made up of one or more concentric bilayers that form when amphiphilic building units self-assemble in water. Because of their potential to localise drug activity at the site or organ of action while reducing its concentration at other places in the body, vesicular drug delivery systems are particularly significant for targeted drug delivery. The vesicular drug delivery system keeps drug activity at a specified rate, keeps drug levels in the body reasonably constant (zero order kinetics), and reduces unwanted side effects at the same time. It can also target medication delivery utilizing carriers or chemical derivatization to localise drug action in the affected tissue or organ. Vesicular drug delivery systems have been used to improve The therapeutic index, solubility, stability, and rapid degradation of a pharmacological molecule are all important factors to consider. As a result, a number of innovative vesicular drug delivery systems that allow drug targeting and prolonged or regulated drug release have been produced. This review will focus on diverse lipoidal and non-lipoidal vesicles, with a special emphasis on pharmaceutical targeting.

 

KEYWORDS: Transdermal Drug Delivery, Vesicular Delivery, Transferosome, Method of preparation, Applications.

 

 


INTRODUCTION:

In most situations, an effective and successful therapeutic therapy is not possible due to a variety of factors, including hepatic first-pass metabolism, undesirable side effects, rejection of invasive treatments, and poor patient compliance. To address these issues, numerous medication delivery systems have been created and studied over the last few decades. Transdermal delivery systems are a promising strategy because they are minimally invasive and have no first-pass effects. However, the skin's barrier function, which blocks or dampens therapeutic agent transdermal transport, must be addressed.1 Transdermal therapy systems are characterized as self-contained, discrete dosage forms that, when applied to intact skin, transport the drug to the systemic circulation at a controlled rate and keep the drug concentration within the therapeutic window for an extended period of time. 2 Niosomes and transferosomes are vesicular carrier systems that have gained a lot of attention in recent decades as a way to deliver drugs transdermally. The features of vesicles structures have been studied in order to improve medication administration within their cavities, as well as to tag the vesicles for cell selectivity. Vesicles are used in transdermal drug administration because they serve as drug carriers, delivering entrapped drug molecules over the skin, and because of their composition, they also act as penetration enhancers.  Furthermore, in the case of topical formulations, these vesicles serve as a depot for the sustained release of active substances, as well as a rate-limiting membrane barrier for the control of systemic absorption in the case of transdermal formulations. 3

 

Advantages:

Vesicular drug delivery systems have a numerous advantages over conventional dosage forms and prolonged-release dosage forms, including the following:4

(i)       Ability to encapsulate both hydrophilic and hydrophobic medicines.

(ii)     Drug bioavailability can also be increased.

(iii)    It is possible to extend the elimination of a fast metabolizable medication.

(iv)    Drugs' circulation life in the body can be extended.

(v)      Drugs can often be delivered in a targeted manner.

(vi)    Liability drug stability difficulties can be overcome.

(vii)   Toxicity problems with specific medications are frequently overcome.

 

Disadvantages:

(i)     Ineffective drug loading.

(ii)    Drug leakage during final product processing and storage.

(iii)   Drug leakage during in vivo transfer.

(iv)   Oxidative lipid degradation.

(v)    Natural phospholipids are not pure.

(vi)   Expensive ingredients.

 

What is the purpose of Vesicular Drug Delivery System (VDDS)?

Due to the restricted diffusion of medicines into cells, conventional chemotherapy for intracellular infections is ineffective. To increase bioavailability at the point of disease, to minimize the undesirable side effects of conventional and controlled release drug delivery methods, and to overcome the problem of drug degradation and/or drug loss.5

 

Types of The targeted vesicles are classified on the basis of their composition:6-7

 

Figure no. 1 Targeted Vesicle

 

Transferosomes:

Transferosomes are vesicular carrier systems with at least one inner aqueous compartment surrounded by a lipid bilayer and an edge activator.A lipid bilayer surrounds the aqueous core, resulting in ultra-deformable vesicles that can self-optimize and regulate themselves. As a result, transferosomes are elastomeric in nature and may bend and squeeze themselves as whole vesicles without discernible loss via skin constrictions or pores that are substantially smaller than the vesicle size. Besides conventional liposomes, which are made up of natural (egg phosphatidylcholine—EPC) or synthetic (dimyristoyl phosphatidylcholine—DPPC, and dipalmitoyl phosphatidyl glycerol—DPPG) phospholipids, the modified liposomal vesicular system (transfersomes) is made up of the phospholipid component and a single-chain surfactant Edge activators (EAs) are membrane- destabilizing factors that increase the deformability of vesicle membranes.8

 

Figure no. 2 Structure of Transferosome

 

When combined in the right ratio with the right lipid, they generate the optimum mix, allowing transfersomes to bend and become ultra-flexible, resulting in improved permeation capability. Transferosomal formulations are widely used in "peripheral drug targeting," "transdermal immunisation," and are widely acknowledged as a primary mechanism for "transdermal delivery" of a wide range of medicinal drugs. Transfersomes are capable of transferring low and large molecular weight (200 MW 106 ) bioactive compounds, as well as hydrophilic and lipophilic molecules, through the skin with a transport efficiency more than 50%, according to several study articles.[9]

 

Table no. 1 Advantages and Disadvantages10

Advantages of Transferosomes

Disadvantages of Transferosomes

Transferosomes can squeeze through pores much smaller than their own diameter because of their strong membrane flexibility.

Due to their tendency for oxidative destruction, transfersomes are chemically unstable. 

They can transport both low and large molecular weight medicines, for example; analgesic, sex hormones, corticosteroids, anticancer, insulin, anaesthetic.

Another factor that works against the use of transfersomes as drug delivery vehicles is the purity of natural phospholipids. 

It's quite easy to combine hydrophilic and hydrophobic medications in it.

This Vesicular system is not cost effective.

They have high entrapement efficiency, in case of lipophilic drug close to 90%

 

They are biocompatible and biodegradable because they are made up of natural phospholipids and EAs.

 

They prevent the encapsulated medication from being degraded metabolically.

 

Transfersomes are an appropriate choice for delivering continuous medication release and a predictable and long-lasting activity.

 

 

Mechanism of transport:11

 

Figure no. 3 Transferosome Mechanism

 

Transferosomes overcome the obstacle of skin penetration by squeezing themselves along the stratum corneum's internal sealing lipids. The method by which transferosomes improve the distribution of active compounds in and across the skin is still unknown. There are two processes by which transferosomes can penetrate the skin:

 

1. Transferosomes are drug vectors that stay intact after passing through the skin. 2. Transferosomes operate as penetration enhancers, breaking the stratum corneum's highly structured intercellular lipids and allowing drug molecules to penetrate into and through the stratum corneum.

 

Cevc and colleagues postulated the first mechanism, claiming that deformable liposomes penetrate the stratum corneum due to the skin's natural transdermal moisture gradient and subsequently enter the systemic circulation after passing the epidermis.

 

Composition of Transferosomes: Transferosomes are generally made up of12

·      First, main ingredient an amphipathic component (e.g. Soya phosphatidylcholine, egg phosphatidylcholine, etc.) that can be a combination of lipids that form the lipid bilayer.

·      Second, biocompatible bilayer-softening chemicals used that increase the vesicles' bilayer flexibility and improve permeability, are the most commonly used edge activators in transferosome preparations.

·      The solvent is approximately 3–10 % alcohol (ethanol or methanol), and the hydrating medium is either water or a saline phosphate buffer (pH 6.5–7).

 

Factors Affecting Transferosomes Formation:13

 

Figure no. 4 Factors affecting Transferosomes 

 

METHOD OF PREPARATION:

A. Thin film hydration process:

This approach consists of three phases and is used to prepare transferosomes.

1.   By dissolving phospholipids and surfactant in a volatile organic solvent, a thin film is made from the vesicles-forming components (chloroform and methanol). A rotary evaporator is used to evaporate the organic solvent. The final one traces of solvent were eliminated overnight.

 

2.   Rotation at 60rpm for 1hour at the appropriate temperature hydrates a prepared thin film with buffer (pH 6.5). The resultant vesicles were enlarged at room temperature for 2 hours.

3. The resulting vesicles were sonicated at room temperature or at 50°C for 30 minutes using a bath sonicator or a probe sonicated at 4°C for 30 minutes to prepare small vesicles. Manual extrusion of the sonicated vesicles 10 times through a sandwich of 200 and 100nm polycarbonate membranes homogenised the vesicles.14-15

 

B. Modified hand shaking:

To create transfersomes, the lipid film hydration technique is also utilised, and it comprises of the following steps:

1.   In a 1:1 mixture of ethanol and chloroform, the drug, lecithin (PC), and edge activator were dissolved. Evaporation of organic solvent while hand shaking above the lipid transition temperature (43°C) was used to remove it. With rotation, a thin lipid coating formed inside the flask wall. The thin coating was left overnight to allow the solvent to evaporate completely. 

2.   The film was then hydrated for 15 minutes at the appropriate temperature with phosphate buffer (pH 7.4) and gentle shaking. At 2-8°C, the transferosome suspension was further hydrated for 1 hour16

 

Characterization of  Transferosome: 17

1.    Vesicle Structure and Shape: Vesicle structure and shape can be characterised by various types of microscopy scanning electron microscopy (SEM), Transmission electron microscopy (TEM), Optical Microscopy, etc.

2.    Size, Size distribution and vesicle diameter: Size, size distribution and diameter of vesicle can be detect by dynamic light scattering (DLS) and photon correlation spectroscopy (PCS).

3.    Entrapewment efficiency (EE): The entrapement efficiency expressed as

 

                                             Amount of drug entrapped

Entrapment efficiency = --------------------------------------- ×100

                                            Total amount of drug added

 

4.    Skin interaction studies: It is common in-vivo methods are confocal microscopy and tape stripping method.

5.    Degree of deformability or permeability measurement: One of the most essential and distinctive parameters in the evaluation of transferosmes is permeability measurement. To determine the degree of distortion for transfersome samples, pure water is used as a benchmark. Depending on the beginning transferosomes suspension, the transferosomes suspension is passed through a sandwich of various micropore filters with pore diameters ranging from 50 nm to 400 nm. Dynamic light scattering (DLS) measurements are used to record particle size and size distribution after each pass.

6.    Turbidity Measurement: A nephelometer is used to detect the turbidity of a sample in an aqueous solution.

7.    Surface charge and charge density: The surface charge and charge density of transferosomes samples are measured using a Zeta sizer.

8.    Penetration ability: The capacity of transferosomes to penetrate is measured using fluorescence microscopy.

9.    Occlusion effect: The ultradeformable vesicles are negatively affected by the occlusion effect. Hydrotaxis, or movement in the direction of water for deeper penetration, is the driving factor for transferosome vesicle migration through the skin. Occlusion affects hydration forces because it prevents water from evaporating from the skin.

10. In- vitro Drug release study: In-vitro drug release can be measured using a diffusion cell or a dialysis method.

11. Drug content may be assessed using HPLC or Spectrophotometric techniques, and vesicle stability can be determined by analysing the size and shape of the vesicle over time.

12. Stability study: Drug content may be assessed using HPLC or spectrophotometric techniques, and vesicle stability can be evaluated by examining the size and structure of the vesicles over time.

 

Applications of Transferosome:18

Transferosomes offer a wide range of uses in the transdermal delivery of drugs and other substances. Ultradeformable vesicle system is used as a carrier for the delivery of:

1.    Insulin

2.    Corticosteroids delivery 

3.    Peptides delivery and targeting of proteins

4.    Interferon delivery 

5.    Anesthetic delivery

6.    NSAIDS

7.    Phytoconstituents

8.    Transdermal immunization

 

Transdermal use of transferosomes for peripheral therapeutic targeting and transdermal immunizations is

also possible.

1. Insulin Delivery: It's a non-invasive method of delivering insulin in the form of transferosomes that has a higher therapeutic response. Insulin is frequently delivered via the subcutaneous method, which is inconvenient and reduces patient compliance. Transfersulin (insulin transferosomes) are made by encapsulating insulin in a deformable vesicle structure, which almost eliminates all issues associated with insulin administration.

2.   Corticosteroids Delivery: Corticosteroids can be given via the skin by integrating them into the vesicular system of transferosomes. By adjusting the amount of medication to be given through the transdermal route, the vesicular system imparts site specificity and safety of corticosteroid drug administration into the deeper region of the skin. To treat specific types of skin problems, a low dosage of corticosteroids in the form of transferosomes is necessary.

3.   Protein and Peptides: Because of their ultradeformable nature, transferosomes can be used to transport and target peptides and proteins. Transferosomes provide a transdermal route for peptide and protein administration, which is preferable to parenteral delivery of these bioactive compounds. The bioavailability of protein provided by dermal route in the form of transferosome was shown to be comparable to that of medication administered via subcutaneous injection in a research.

4.   Interferon delivery: Transferosomes can transport naturally occurring protein interferons with antiproliferative, antiviral, and immunomodulatory properties, such as interferon-a from leukocytes (INF-a). The transfersome vesicular formulation of interferon-a and interleukin-2 is said to provide the finest cutaneous outcomes. The administration of IL-2 and INF-a in the form of transferosomes for immune treatment shows superior outcomes in terms of concentration.

5.   Anesthetic delivery: The use of anaesthetics in the suspension of transferosomes generates topical anaesthesia within 10 minutes under ideal conditions. Transferosomal anaesthetics have a longer duration of action than subcutaneous bolus injections.

6.   Non- steroidal anti-inflammatory drugs: The majority of the medications in the non-steroidal anti-inflammatory (NSAID) group have a variety of gastrointestinal adverse effects. Such issues can be addressed by integrating them into ultra-deformable vesicles that are applied via the cutaneous route.

7.   Phytoconstituents: The ultradeformable vesicular system has the potential to penetrate deeper into the skin towards the stratum corneum and transport nutrients via the dermal pathway for regular skin function. Capsaicin transferosomes have been shown to have superior absorption than capsaicin (pure).

8.   Transdermal immunization: This is one of transferosomes' most essential uses. Transferosomes containing soluble proteins such as integral membrane protein, human serum albumin, and gap junction protein are used in the transdermal vaccination. This is a non-invasive vaccination strategy that produces superior outcomes.

 

CONCLUSION:

Transferosome formulation could be useful to reduce the unwanted side effects. It could be ideal vesicular carrier for administration via skin.." Transferosomes due to their high deformability can incorporate large molecular weight drugs, both hydrophilic and lipophilic drugs. Transferosomes are particularly constructed vesicles that can respond to external stress by squeezing themselves through skin pores that are many times smaller than they are, increasing transdermal flow.

 

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Received on 12.01.2022        Modified on 17.04.2022

Accepted on 10.06.2022   ©AandV Publications All Right Reserved

Res.  J. Pharma. Dosage Forms and Tech.2022; 14(3):206-210.

DOI: 10.52711/0975-4377.2022.00033