Ashokrao Mane College of Pharmacy, Peth Vadgaon Maharashtra, India.
Two conventional drug administration methods that have several drawbacks are oral and intravenous routes. Oral medications go through tough conditions in the digestive system. They may be hard to dissolve, break down too quickly due to different acid levels, or get processed by the liver before they can work properly. Intravenous (IV)formulations are effective at delivering drugs directly into the bloodstream, but they also include risks such as embolism, infection, and needle discomfort. In addition, many patients find it difficult to adhere to their medication regimens due to unpleasant injections or taste. Transferosomes are vesicles that can contain drugs and are made of phospholipids that resemble human cell membranes. What sets transferosomes apart is the inclusion of edge activators, which are chemicals that further enhance their flexibility. Transferosomes' increased flexibility allows themto enter even the smallest skin pores and adapt to various body situations, such as moisture levels. Transferosomes are vesicles that can contain drugs and are made of phospholipids that resemble human cell membranes. What sets transferosomes apart is the inclusion of edge activators, which are chemicals that further enhance their flexibility. Transferosomes' increased flexibility allows themto enter even the smallest skin pores and adapt to various body situations, such as moisture levels.
"Transferosome," a trademark of the German company IDEA AG, alludes to their proprietary medicine delivery system. In essence, the term means "carrying body" since it combines the Latin transferre, which means "to carry across," and the Greek word soma, which means "body"[1]. Transferosomes are synthetic vesicles that mimic the functions of natural cell vesicles. It helps medications pass through the body more efficiently by simulating how compounds are normally moved by cells. Because of this, it is an effective and controlled instrument for delivering drugs to the right place helping to deliver drugs in a controlled and targeted way [2]. Complex vesicles known as transfersomes are highly deformable due to the very flexible and self-regulating membranes. A special type of pharmaceutical delivery system is being developed in order to attain high therapeutic activity and patient compliance. Improvements in therapeutic action have led to the development of numerous medication delivery methods; However, several of these systems have unresolved problems[3].Drugs taken orally encounter a gastrointestinal(GI) tract is a harsh environment where most medications breakdown due to different acid levels, have trouble dissolving, and, most importantly, go through first-pass metabolism[4].The absence of medicine reversal, hypersensitive reaction and the potential for infection, embolism, and cost are among the drawbacks of intravenous formulation. Patients' adherence is reduced by the disagreeable taste of some medications, the difficulty of digesting them when administered orally, and the discomfort of the needle when administered parenterally. The route through the skin has recently been one of the most innovative and successful areas of focus for drug delivery research, with more than 40% of Transferosomes are sophisticated drug delivery systems that have a high rate of effectiveness when delivering drugs deep into the body [5].Lipids (molecules that resemble fat) and surfactants (agents that aid in the mixing of water and oil) combine to form these incredibly flexible, tiny structures. Transferosomes are made to fit through microscopic pores in the skin or other biological barriers, which makes drug administration more effective and efficient than typical drug carriers[6].By administering drugs through the skin (transdermal administration), they are especially beneficial in reducing the need for injections or oral therapy. The essential elements of transferosomes are their flexibility and structure. Phospholipids, which resemble the substances that makeup human cell membranes, make the mup. These phospholipids form a tiny bubble called a vesicle that can transport medications [7]. Transferosomes are special because they contain an edge activator, a material that gives them extreme flexibility. Because of their adaptability, they can easily breach even the smallest biological barriers. Transferosomes react to the body's moisture levels when applied to the skin or another surface, forcing themselves through even the smallest pores.They are better than conventional liposomes, another kind of drug carrier, because of their capacity to distort and fit through small openings. Transferosomes increase the drug's effectiveness by releasing it gradually once it is inside the body.
Structure and Composition of Transfersome: [9]
Making transfersomes requires various ingredients like phospholipids, alcohol, surfactants, colorants, and buffering agents. The complete list of ingredients used in transfersomes is given below.
Fig 1. Structure of Transferosome
Mechanism Of Action: [10]
Fig2.Mechanism of Action
Benefits Of Transferosomes: [11, 12]
There are several ways in which transferosomes are better than traditional medication delivery methods.
Drawbacks: [13]
Transferosome Material;[15]
Transfersomes are made of phospholipids like phosphatidylcholine and form flexible, self-assembling vesicles in water. These vesicles create a lipid bilayer, which can hold and deliver drugs. To make the bilayer more flexible and improve drug delivery, a softening agentis added. The flexibility of the transfersome membrane can be adjusted by using the right combination of surface-active agents. This allows transfersomes to change shape easily based on surrounding conditions, reducing the risk of breaking apart when applied to the skin. Transfersomes are designed to move through the skin by following the natural water flow in the epidermis. They are mainly made of phospholipids, along with a moisturizing solution and10-25% surfactants (such as ethanol or methanol) for flexibility. Dyes like Rhodamine 123 and Nile Red are sometimes used for imaging in laser microscopy studies [16].
The table below provides an overview of the materials frequently used to prepare transfersomes [17].
|
Ingredient |
Examples |
Function |
|
Phospholipid |
Soy phosphatidylcholine, egg phosphatidylcholine, distearoyl phosphatidylcholine |
Forms vesicles |
|
Surfactant |
Sodium choate, sodium deoxycholate, Tween 80, Span 80 |
Provides flexibility |
|
Alcohol |
Ethanol, methanol |
Used As a solvent |
|
Dye |
Rhodamine-123, Rhodamine-DHPE, Fluorescein-DHPE, Nile red, 6- Carboxyfluorescein |
Used For Imaging in Confocal Scanning Laser Microscopy studies |
|
Buffering Agent |
Saline phosphate buffer(pH6.5),7% v/v ethanol, Tris buffer (pH 6.5) |
Used As a Hydrating medium |
Method of Preparation:
Transfersomes are made using a three-step thin film hydration procedure [18].
Fig3.Thin Film Hydration Method
Vertexing Sonication Method [19]
Phospholipids, the active drug, and an edge activator are first mixed in a phosphate-buffered saline (PBS) solution. The mixure is then vortexed until it becomes uniform, milk like-white suspension. After vortexing, it is briefly treated with sound waves (sonication) to further refine it.
Fig4.Vortexingsonication Method
Freeze-Thaw Method [20]
In this technique, a suspension of multi lamellar vesicles is first frozen at an extremely low temperature. Then, it is thawed by placing the tube in a hot water bath. This freezing and thawing process is continued8–9 times to refine the vesicles.
Fig5.Freeze-Thaw Method
The Method of Reverse Phase Evaporation [21]
Organic solvents and lipids are combined in a flask. Following nitrogen gas removal of oxygen, a water-based solution containing edge activators is added. Based on how well the drug dissolves, it is introduced to either the lipid solution or the water solution. After that, sound waves (sonication) are applied to the mixture for at least halfan hourto ensure that it is well combined. A thick gel that eventually takes the form of vesicles is produced by removing the organic solvent under low pressure. Filtration or centrifugation are used to get rid of any remaining solvent or medicine that wasn't absorbed.
Fig6.Reverse Phase Evaporation Method Factors Affecting Transfersome:
Throughout the process of developing an ideal formulation, a variety of procedural variables may affect the transfersome characteristics. The following indicate the factors that are mostly related to the creation of transfersome formulations:
The size, charge, and ability of vesicles to carry drugs depend on several factors. These include how well the surfactant balances water and oil (HLB value), how the molecules fit into the lipid layer, how much the head group attracts water, the length and number of carbon chains in the surfactant, and its concentration [22]. Smaller vesicles are usually formed when the head group attracts more water, the carbon chains are longer and more frequent, the HLB value is higher, and the surfactant concentration is greater [23].
Two typical solvents are methanol and ethanol.Reliability and compatibility with the formulation are key factors in selecting the best solvent .All ingredients drug and other additives must dissolve fully in the solvent to create a transparent solution for a stable and efficient film [24]. More of the medication can cross a membrane when solvents are used to improve penetration. According to research, ethanol improves the way that some medications are absorbed through the skin of rats (William and Barry, 2004) [25].
When exposed to external pressure, transfersomes extremely flexible lipid vesicles have been specially designed to exhibit the remarkable ability to rapidly deform. This characteristic facilitates their passage through the vesicles because the pores present in skin are smaller than the vesicles themselves [26].Some edge activators and the concentrations of these activators are necessary to optimize membrane deformability. This enhancement is attributed to permeability enhancers and transfersomes' combined efficacy as drug carriers [27].
Choosing between water and saline phosphate buffer is crucial for achieving the best possible balance in the formulation qualities, biological applicability, and distribution mechanism. The pH level of the hydration medium must be maintained within a certain range in order to maintain the drug in its unionized form, enhance its trapping inside transfersomes, and facilitate its passage through the cellular membrane. This is particularly crucial since the medications can be delivered within cells because the lipid bilayer of the transfersome and the phospholipid layer of the cell membrane are comparable [28].
Characteristics of Transfersome:
1. Entrapment Effectiveness: [29]
Using the centrifuge method, the percentage of drug trapped inside the transfersomes was determined. First, 10 milimeters of phosphate buffer solution at pH 6,8 or 7 taken. This was combined with 100 milligrams of the transferosomal formulation,which had been weighed. A centrifuge was then used to spin this combination for 40 minutes at 10,000 rpm.
Following centrifugation, the amount of free medication was measured by analyzing the transparent liquid.
2. Vesicles size distribution and zeta potential analysis:
Zetasizer, which offered information on the average diameter, size distribution profile, and zeta potential, was used to analyze vesicles. Penetrative ability of the transfersome was determined by assessing the vesicles' durability and colloidal characteristics.
3. Degree of deformability:[31]
The deformability of transfersomal formulation was investigated using a handmade apparatus. The experiment involved forcing vesicle suspension through a polycarbonate filter, and measuring the tracking size and suspension volume before and after filtering. To calculate the degree of deformability, a formula was utilized.
4.Turbidity and Vesicle Size Measurement [32]
The cloudiness of different formulations was measured using a Nephelometer, with phosphate buffer solution at pH 6.5 or 7 as a reference. The vesicle size was determined using photon correlation spectroscopy or dynamic light scattering.
5. Stability Testing [33]
To check how stable the transfersome formulation is, samples were stored at 4°C to 25°C for 21 days.
Measurements were taken at 0, 7, 14, and 21days to track:
How much drug stayed inside the vesicles (EE)
The electric charge on vesicles, which affects stability (ZP) The size of the vesicles.
How even analysed the vesicles are (PDI)
This test helped to see if the formulation remained stable overtime.
6. In vitro study (Drug release kinetics): [34]
By use of a Franz diffusion cell, the amount of drug that passed through the hairless rat skin was measured in this study. The phosphate buffer saline and an elastic liposome solution were placed in one of the two chambers that encased the epidermis. About 37°C was maintained as the constant temperature in the setup. Each day, samples were taken to monitor drug penetration. To measure the amount of the medication that went through the skin, an HPLC approach was employed. After that, scientists determined the drug's rate of passage through the skin, its time to begin penetrating, and its rate over time.
7. Confocal laser scanning microscopy study:[35]
A detailed analysis of the skin's structure and function was conducted using confocal laser scanning microscopy. Flexible, fluorescently stained vesicles known as transsomes were applied topically by researchers. With this method, they could simultaneously track fluorescent markers and use reflected light to look at the structure of the skin.
8.Occlusion Effect:[36]
For traditional topical medications, covering the skin(occlusion) helps the drug absorb better[38]. However, for elastic vesicles, this can actually be harmful. These vesicles move through the skin by a process called hydrotaxis. When the skin is covered, less water evaporates, which changes the hydration balance and can interfere with how the vesicles move.
Applications of Transfersome:
1. Transfersomes help keep delicate medicines stable and allow for their slow, controlled release by using phospholipids [37].
2. Due to the fact that transfersomes 'bioavailability is similar to that of subcutaneous injection. It was discovered that human serum albumin encapsulated in transfersomes may effectively elicit the immune response when administered transdermally [38].
3. Transdermal Immunization: Studies on skin-based Hepatitis B vaccinations have shown promising results. When zidovudine was used instead ofthe usual control, the drug levels in the body were 12 times higher [39]. Additionally, the drug was the more effectively targeted to the reticulo endothelial system (RES), where HIV is often found [40]
4. NSAIDs can cause various stomach related side effects. However, delivering them through the skin using ultra-flexible vesicles can help avoid these issues [41].
5. They are commonly used to deliver proteins and peptides into the body. These molecules are large and difficult to absorb, and if taken by mouth, they breakdown completely in the digestive system [42]. Because of this, injections are still needed to get the mint to the body [43]. Researchers have developed different methods to improve this process, and transferosomes have been found to be just as effective as injecting the same protein under the skin [44].
6. Using transferosomes to deliver insulin through the skin is an effective and painless way to administer this large molecule drug [45]. Normally, insulin is given through injections, which can be inconvenient and uncomfortable. However, when insulin is enclosed in transferosomes (called "transfersulin"), the issues are resolved [46]. Once applied to intact skin, transfersulin starts lowering blood sugar within 90 to180 minutes, depending on the type of carrier used [47].
CONCLUSION:
Specialized particles or vesicles known as transfersomes have the ability to rapidly and affordably alter their shape in response to outside stimuli. Thus flexible particles can be used to deliver drugs. They can nearly as easily pass through even the smallest holes (100mm) even though they are 1500 times smaller than water. Drug loaded transfersomes can carry upto 100mg cm 2h 1 of medication through the skin in a previously unheard of amount of time. The difficulty to transport larger molecules and the fact that drug penetration through the stratum corneum is a rate limiting step are two major disadvantages of the transdermal drug delivery method, despite its many benefits over alternative drug delivery routes.Vesicular systems such as transfersomes were developed to overcome these barriers. It is more effective and safer than others due to its makeup. Depending on needs drug release can be controlled. Thus, the problems that come up with conventional methods can be resolved by this method.
REFERENCES
Kalugade Sanika*, Deshmukh Akshta, A Review on Promising Approach of Transferosomes for Topical and Transdermal Drug Delivery, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 4, 995-1006 https://doi.org/10.5281/zenodo.15181562
10.5281/zenodo.15181562
