Encapsulation Techniques Applied to Pharmaceutics

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 48199

Special Issue Editors

Department of Pharmacy, National University of Singapore, 21 Lower Kent Ridge Rd, Singapore 119077, Singapore
Interests: pharmaceutical technology, in areas of coating, pelletization, microencapsulation, powder technology, preparation of botanicals, controlled release formulations, and process science
Special Issues, Collections and Topics in MDPI journals
Heine Pharmacy Building, 575 Stadium Mall Drive, Purdue University, West Lafayette, IN 47907-2091, USA
Interests: pharmaceutical technology, in areas of preformulation and formulation of solid dosage forms

Special Issue Information

Dear Colleagues,

Advances in drug discovery have led to the requirement of developing more specialized and targeted delivery systems for highly potent and target-specific drug candidates. Despite showing great promise during early-stage development, many of these candidates often fail during preclinical and clinical stages due to challenges associated with effective drug delivery. For small molecules, factors such as poor stability and solubility are often a hindrance to successful product development, while large molecules such as peptides and proteins face the problem of maintaining their therapeutic efficacy until delivered at the site of action. Additionally, with the emergence of nanotechnology, better targeted and site-specific drug delivery systems have been developed to promote the accumulation of drugs at target sites while avoiding undesirable systemic side-effects. Encapsulation is one of the promising drug delivery strategies to tackle some of these difficult issues. Emerging encapsulation technologies have tailored encapsulated products to achieve very specific roles, ranging from targeted drug delivery to controlled drug release. For oral delivery systems, with the aims of taste masking, target specificity or controlled release, there is a need for better coating media and techniques, especially for encapsulating smaller particles, which can be challenging.   

This Special Issue serves to capture the advances and innovations in encapsulation technologies, and the use of encapsulation for drug delivery. In particular, this issue will also highlight the progress in the preparation and characterization encapsulated drug particles, as well as its application in pharmacotherapy.

Prof. Dr. Paul W S Heng
Dr. Tze Ning Hiew
Guest Editors

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Keywords

  • encapsulation
  • drug delivery
  • nanoparticles
  • microparticles
  • pellets
  • coatings

Published Papers (11 papers)

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Research

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16 pages, 2747 KiB  
Article
Hyaluronic Acid-Based Nanoparticles for Protein Delivery: Systematic Examination of Microfluidic Production Conditions
by Enrica Chiesa, Antonietta Greco, Federica Riva, Rossella Dorati, Bice Conti, Tiziana Modena and Ida Genta
Pharmaceutics 2021, 13(10), 1565; https://doi.org/10.3390/pharmaceutics13101565 - 26 Sep 2021
Cited by 10 | Viewed by 2687
Abstract
Hyaluronic acid-based nanoparticles (HA NPs) can be used to deliver a protein cargo to cells overexpressing HA receptors such as CD44 since they combine the low toxicity of the carrier and the retention of the protein integrity with the receptor-mediated internalization. HA properties [...] Read more.
Hyaluronic acid-based nanoparticles (HA NPs) can be used to deliver a protein cargo to cells overexpressing HA receptors such as CD44 since they combine the low toxicity of the carrier and the retention of the protein integrity with the receptor-mediated internalization. HA properties play a crucial but sometimes unclear role in managing the formation and stability of the meshwork, cell interactions, and ultimately the protein entrapment efficacy. Nowadays, microfluidic is an innovative technology that allows to overcome limits linked to the NPs production, guaranteeing reproducibility and control of individual batches. Taking advantage of this technique, in this research work, the role of HA weight average molecular weight (Mw) in NPs formation inside a microfluidic device has been specifically faced. Based on the relationship between polymer Mw and solution viscosity, a methodological approach has been proposed to ensure critical quality attributes (size of 200 nm, PDI ≤ 0.3) to NPs made by HA with different Mw (280, 540, 710 and 820 kDa). The feasibility of the protein encapsulation was demonstrated by using Myoglobin, as a model neutral protein, with an encapsulation efficiency always higher than 50%. Lastly, all NPs samples were successfully internalized by CD44-expressing cells. Full article
(This article belongs to the Special Issue Encapsulation Techniques Applied to Pharmaceutics)
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10 pages, 4264 KiB  
Article
A New Approach for the Microencapsulation of Clitoria Ternatea Petal Extracts by a High-Pressure Processing Method
by Hua-Wei Chen, Yu-Wei Chang and Wu-Po Fang
Pharmaceutics 2021, 13(1), 23; https://doi.org/10.3390/pharmaceutics13010023 - 24 Dec 2020
Cited by 7 | Viewed by 2187
Abstract
Toxic organic solvent residues and the active substances of thermal degradation (such as anthocyanin and polyphenols) are always a concern with the liposomes produced by traditional techniques. The present study focuses on a new approach for the microencapsulation of Clitoria ternatea petal (CTP) [...] Read more.
Toxic organic solvent residues and the active substances of thermal degradation (such as anthocyanin and polyphenols) are always a concern with the liposomes produced by traditional techniques. The present study focuses on a new approach for the microencapsulation of Clitoria ternatea petal (CTP) extracts, which contain anthocyanins, by high-pressure processing (HPP) at room temperature. Thus, a series of CTP liposomes were prepared and their physicochemical properties were analyzed by laser granulometry and by scanning electron microscopy (SEM). The results revealed that the average particle size of the liposomes after HPP treatment increased gradually from 300 MPa to 600 MPa, possibly due to the aggregation of liposomes and damage to the phospholipid bilayers. For the preparation of liposomes by the HPP method at 300 MPa, the mean particle size, polydispersity index (PDI), and encapsulation efficiency were 240.7 nm, 0.37, and 77.8%, respectively. The HPP method provided a number of advantages over conventional methods (magnet stirring and ultrasonication) as it could allow liposome preparation with higher encapsulation efficiency, smaller size, and narrower, more reproducible particle size distribution. Conclusively, microencapsulation in the liposomes was successfully achieved with the fast-adiabatic expansion of HPP. Full article
(This article belongs to the Special Issue Encapsulation Techniques Applied to Pharmaceutics)
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16 pages, 42394 KiB  
Article
Encapsulation of Activated Carbon into a Hollow-Type Spherical Bacterial Cellulose Gel and Its Indole-Adsorption Ability Aimed at Kidney Failure Treatment
by Toru Hoshi, Masahito Endo, Aya Hirai, Masashige Suzuki and Takao Aoyagi
Pharmaceutics 2020, 12(11), 1076; https://doi.org/10.3390/pharmaceutics12111076 - 11 Nov 2020
Cited by 5 | Viewed by 2708
Abstract
For reducing side effects and improvement of swallowing, we studied the encapsulation of activated carbon formulations with a hollow-type spherical bacterial cellulose (HSBC) gel using two kinds of encapsulating methods: Methods A and B. In Method A, the BC gelatinous membrane was biosynthesized [...] Read more.
For reducing side effects and improvement of swallowing, we studied the encapsulation of activated carbon formulations with a hollow-type spherical bacterial cellulose (HSBC) gel using two kinds of encapsulating methods: Methods A and B. In Method A, the BC gelatinous membrane was biosynthesized using Komagataeibacter xylinus (K. xylinus) at the interface between the silicone oil and cell suspension containing activated carbon. In Method B, the bacterial cellulose (BC) gelatinous membrane was formed at the interface between the cell suspension attached to the alginate gel containing activated carbon and the silicone oil. After the BC gelatinous membrane was biosynthesized by K. xylnus, alginate gel was removed by soaking in a phosphate buffer. The activated carbon encapsulated these methods could neither pass through the BC gelatinous membrane of the HSBC gel nor leak from the interior cavity of the HSBC gel. The adsorption ability was evaluated using indole, which is a precursor of the uremic causative agent. From curve-fitting, the adsorption process followed the pseudo-first-order and intra-particle diffusion models, and the diffusion of the indole molecules at the surface of the encapsulated activated carbon within the HSBC gel was dominant at the initial stage of adsorption. It was observed that the adsorption of the encapsulated activated carbon by the intraparticle diffusion process became dominant with longer adsorption times. Full article
(This article belongs to the Special Issue Encapsulation Techniques Applied to Pharmaceutics)
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18 pages, 2364 KiB  
Article
Design and Characterization of Ethosomes for Transdermal Delivery of Caffeic Acid
by Supandeep Singh Hallan, Maddalena Sguizzato, Paolo Mariani, Rita Cortesi, Nicolas Huang, Fanny Simelière, Nicola Marchetti, Markus Drechsler, Tautgirdas Ruzgas and Elisabetta Esposito
Pharmaceutics 2020, 12(8), 740; https://doi.org/10.3390/pharmaceutics12080740 - 06 Aug 2020
Cited by 49 | Viewed by 4682
Abstract
The present investigation describes a formulative study aimed at designing ethosomes for caffeic acid transdermal administration. Since caffeic acid is characterized by antioxidant potential but also high instability, its encapsulation appears to be an interesting strategy. Ethosomes were produced by adding water into [...] Read more.
The present investigation describes a formulative study aimed at designing ethosomes for caffeic acid transdermal administration. Since caffeic acid is characterized by antioxidant potential but also high instability, its encapsulation appears to be an interesting strategy. Ethosomes were produced by adding water into a phosphatidylcholine ethanol solution under magnetic stirring. Size distribution and morphology of ethosome were investigated by photon correlation spectroscopy, small-angle X-ray spectroscopy, and cryogenic transmission electron microscopy, while the entrapment capacity of caffeic acid was evaluated by high-performance liquid chromatography. Caffeic acid stability in ethosome was compared to the stability of the molecule in water, determined by mass spectrometry. Ethosome dispersion was thickened by poloxamer 407, obtaining an ethosomal gel that was characterized for rheological behavior and deformability. Caffeic acid diffusion kinetics were determined by Franz cells, while its penetration through skin, as well as its antioxidant activity, were evaluated using a porcine skin membrane–covered biosensor based on oxygen electrode. Ethosome mean diameter was ≈200 nm and almost stable within three months. The entrapment of caffeic acid in ethosome dramatically prolonged drug stability with respect to the aqueous solution, being 77% w/w in ethosome after six months, while in water, an almost complete degradation occurred within one month. The addition of poloxamer slightly modified vesicle structure and size, while it decreased the vesicle deformability. Caffeic acid diffusion coefficients from ethosome and ethosome gel were, respectively, 137- and 33-fold lower with respect to the aqueous solution. At last, the caffeic acid permeation and antioxidant power of ethosome were more intense with respect to the simple solution. Full article
(This article belongs to the Special Issue Encapsulation Techniques Applied to Pharmaceutics)
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19 pages, 2939 KiB  
Article
Formulation and Characterisation of a Combination Captopril and Hydrochlorothiazide Microparticulate Dosage Form
by Mellisa T. R. Chikukwa, Roderick B. Walker and Sandile M. M. Khamanga
Pharmaceutics 2020, 12(8), 712; https://doi.org/10.3390/pharmaceutics12080712 - 30 Jul 2020
Cited by 13 | Viewed by 4701
Abstract
Cardiovascular diseases such as hypertension and cardiac failure in South African children and adolescents are effectively managed long term, using a combination treatment of captopril and hydrochlorothiazide. The majority of commercially available pharmaceutical products are designed for adult patients and require extemporaneous manipulation, [...] Read more.
Cardiovascular diseases such as hypertension and cardiac failure in South African children and adolescents are effectively managed long term, using a combination treatment of captopril and hydrochlorothiazide. The majority of commercially available pharmaceutical products are designed for adult patients and require extemporaneous manipulation, prior to administration to paediatric patients. There is a need to develop an age appropriate microparticulate dosing technology that is easy to swallow, dose and alter doses whilst overcoming the pharmacokinetic challenges of short half-life and biphasic pharmacokinetic disposition exhibited by hydrochlorothiazide and captopril. An emulsion solvent evaporation approach using different combinations of polymers was used to manufacture captopril and hydrochlorothiazide microparticles. Design of experiments was used to develop and analyse experimental data, and identifyoptimum formulation and process conditions for the preparation of the microparticles. Characterisation studies to establish encapsulation efficiency, in vitro release, shape, size and morphology of the microparticles were undertaken. The microparticles produced were in the micrometre size range, with an encapsulation efficiency >75% for both hydrochlorothiazide and captopril. The microparticulate technology is able to offer potential resolution to the half-life mediated dosing frequency of captopril as sustained release of the molecule was observed over a 12-h period. The release of hydrochlorothiazide of >80% suggests an improvement in solubility limited dissolution. Full article
(This article belongs to the Special Issue Encapsulation Techniques Applied to Pharmaceutics)
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17 pages, 1644 KiB  
Article
Pharmacological and Advanced Cell Respiration Effects, Enhanced by Toxic Human-Bile Nano-Pharmaceuticals of Probucol Cell-Targeting Formulations
by Susbin Raj Wagle, Bozica Kovacevic, Daniel Walker, Corina Mihaela Ionescu, Melissa Jones, Goran Stojanovic, Sanja Kojic, Armin Mooranian and Hani Al-Salami
Pharmaceutics 2020, 12(8), 708; https://doi.org/10.3390/pharmaceutics12080708 - 29 Jul 2020
Cited by 24 | Viewed by 2725
Abstract
Bile acids have recently been studied for potential applications as formulation excipients and enhancers for drug release; however, some bile acids are not suitable for this application. Unconjugated lithocholic acid (ULCA) has recently shown drug formulation-stabilizing and anti-inflammatory effects. Lipophilic drugs have poor [...] Read more.
Bile acids have recently been studied for potential applications as formulation excipients and enhancers for drug release; however, some bile acids are not suitable for this application. Unconjugated lithocholic acid (ULCA) has recently shown drug formulation-stabilizing and anti-inflammatory effects. Lipophilic drugs have poor gut absorption after an oral dose, which necessitates the administration of high doses and causes subsequent side effects. Probucol (PB) is a highly lipophilic drug with poor oral absorption that resulted in restrictions on its clinical prescribing. Hence, this study aimed to design new delivery systems for PB using ULCA-based matrices and to test drug formulation, release, temperature, and biological effects. ULCA-based matrices were formulated for PB oral delivery by applying the jet-flow microencapsulation technique using sodium alginate as a polymer. ULCA addition to new PB matrices improved the microcapsule’s stability, drug release in vitro (formulation study), and showed a promising effect in ex vivo study (p < 0.05), suggesting that ULCA can optimize the oral delivery of PB and support its potential application in diabetes treatment. Full article
(This article belongs to the Special Issue Encapsulation Techniques Applied to Pharmaceutics)
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16 pages, 2508 KiB  
Article
Assessment of Residual Solvent and Drug in PLGA Microspheres by Derivative Thermogravimetry
by Hyunjin Shim and Hongkee Sah
Pharmaceutics 2020, 12(7), 626; https://doi.org/10.3390/pharmaceutics12070626 - 04 Jul 2020
Cited by 11 | Viewed by 2512
Abstract
Thermogravimetry does not give specific information on residual organic solvents in polymeric matrices unless it is hyphenated with the so-called evolved gas analysis. The purpose of this study was to apply, for the first time, derivative thermogravimetry (DTG) to characterize a residual solvent [...] Read more.
Thermogravimetry does not give specific information on residual organic solvents in polymeric matrices unless it is hyphenated with the so-called evolved gas analysis. The purpose of this study was to apply, for the first time, derivative thermogravimetry (DTG) to characterize a residual solvent and a drug in poly-d,l-lactide-co-glycolide (PLGA) microspheres. Ethyl formate, an ICH class 3 solvent, was used to encapsulate progesterone into microspheres. DTG provided a distinct peak, displaying the onset and end temperatures at which ethyl formate started to evolve from to where it completely escaped out of the microspheres. DTG also gave the area and height of the solvent peak, as well as the temperature of the highest mass change rate of the microspheres. These derivative parameters allowed for the measurement of the amount of residual ethyl formate in the microspheres. Interestingly, progesterone affected not only the residual solvent amount but also these derivative parameters. Another intriguing finding was that there was a linear relationship between progesterone content and the peak height of ethyl formate. The residual solvent data calculated by DTG were quite comparable to those measured by gas chromatography. In summary, DTG could be an efficient and practical quality control tool to evaluate residual solvents and drugs in various polymeric matrices. Full article
(This article belongs to the Special Issue Encapsulation Techniques Applied to Pharmaceutics)
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19 pages, 4045 KiB  
Article
High Efficiency Vibrational Technology (HEVT) for Cell Encapsulation in Polymeric Microcapsules
by Silvia Pisani, Rossella Dorati, Ida Genta, Enrica Chiesa, Tiziana Modena and Bice Conti
Pharmaceutics 2020, 12(5), 469; https://doi.org/10.3390/pharmaceutics12050469 - 21 May 2020
Cited by 6 | Viewed by 2595
Abstract
Poly(methyl-methacrylate) (PMMA) is a biocompatible and non-biodegradable polymer widely used as biomedical material. PMMA microcapsules with suitable dimension and porosity range are proposed to encapsulate live cells useful for tissue regeneration purposes. The aim of this work was to evaluate the feasibility of [...] Read more.
Poly(methyl-methacrylate) (PMMA) is a biocompatible and non-biodegradable polymer widely used as biomedical material. PMMA microcapsules with suitable dimension and porosity range are proposed to encapsulate live cells useful for tissue regeneration purposes. The aim of this work was to evaluate the feasibility of producing cell-loaded PMMA microcapsules through “high efficiency vibrational technology” (HEVT). Preliminary studies were conducted to set up the process parameters for PMMA microcapsules production and human dermal fibroblast, used as cell model, were encapsulated in shell/core microcapsules. Microcapsules morphometric analysis through optical microscope and scanning electron microscopy highlighted that uniform microcapsules of 1.2 mm with circular surface pores were obtained by HEVT. Best process conditions used were as follows: frequency of 200 Hz, voltage of 750 V, flow rate of core solution of 10 mL/min, and flow rate of shell solution of 0.5 bar. Microcapsule membrane allowed permeation of molecules with low and medium molecular weight up to 5900 Da and prevented diffusion of high molecular weight molecules (11,000 Da). The yield of the process was about 50% and cell encapsulation efficiency was 27% on total amount. The cell survived and growth up to 72 h incubation in simulated physiologic medium was observed. Full article
(This article belongs to the Special Issue Encapsulation Techniques Applied to Pharmaceutics)
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13 pages, 2464 KiB  
Article
Synthesis and Characterization of Polyfumarateurethane Nanoparticles for Sustained Release of Bupivacaine
by Soo-Yong Park, Jiin Kang, Ji-Young Yoon and Ildoo Chung
Pharmaceutics 2020, 12(3), 281; https://doi.org/10.3390/pharmaceutics12030281 - 21 Mar 2020
Cited by 4 | Viewed by 2965
Abstract
Biodegradable polyfumarateurethane (PFU) for use as a bupivacaine delivery vehicle, synthesized using di-(2-hydroxypropyl fumarate) (DHPF), polyethylene glycol (PEG) and 1,6-hexamethylene diisocyanate (HMDI), was designed to be degradable through the hydrolysis and enzymatic degradation of the ester bonds in its polymer backbone. Using a [...] Read more.
Biodegradable polyfumarateurethane (PFU) for use as a bupivacaine delivery vehicle, synthesized using di-(2-hydroxypropyl fumarate) (DHPF), polyethylene glycol (PEG) and 1,6-hexamethylene diisocyanate (HMDI), was designed to be degradable through the hydrolysis and enzymatic degradation of the ester bonds in its polymer backbone. Using a water-in-oil-in-water double emulsion techniques, nanoparticles encapsulating water or fluorescein isothiocyanate (FITC) were fabricated to avoid the immune system owing to the presence of PEG on their surface. The morphologies of these nanoparticles were characterized by DLS, TEM, FE-SEM, and fluorescent microscopies. The present study explored the encapsulation, loading efficiency and in vitro drug release of bupivacaine encapsulated with biodegradable PFU nanoparticles for the treatment of local anesthesia. Various concentrations of bupivacaine were encapsulated into nanoparticles and their encapsulation efficiencies and drug loading were investigated. Encapsulation efficiency was highest when 2.5% bupivacaine was encapsulated. Drug release behavior from the bupivacaine-loaded PFU nanoparticles followed a sustained release profile. Full article
(This article belongs to the Special Issue Encapsulation Techniques Applied to Pharmaceutics)
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28 pages, 4419 KiB  
Article
Improved Stability of Rifampicin in the Presence of Gastric-Resistant Isoniazid Microspheres in Acidic Media
by Chiluba Mwila and Roderick B. Walker
Pharmaceutics 2020, 12(3), 234; https://doi.org/10.3390/pharmaceutics12030234 - 05 Mar 2020
Cited by 17 | Viewed by 4941
Abstract
The degradation of rifampicin (RIF) in an acidic medium to form 3-formyl rifamycin SV, a poorly absorbed compound, is accelerated in the presence of isoniazid, contributing to the poor bioavailability of rifampicin. This manuscript presents a novel approach in which isoniazid is formulated [...] Read more.
The degradation of rifampicin (RIF) in an acidic medium to form 3-formyl rifamycin SV, a poorly absorbed compound, is accelerated in the presence of isoniazid, contributing to the poor bioavailability of rifampicin. This manuscript presents a novel approach in which isoniazid is formulated into gastric-resistant sustained-release microspheres and RIF into microporous floating sustained-release microspheres to reduce the potential for interaction between RIF and isoniazid (INH) in an acidic environment. Hydroxypropyl methylcellulose acetate succinate and Eudragit® L100 polymers were used for the manufacture of isoniazid-loaded gastric-resistant sustained-release microspheres using an o/o solvent emulsification evaporation approach. Microporous floating sustained-release microspheres for the delivery of rifampicin in the stomach were manufactured using emulsification and a diffusion/evaporation process. The design of experiments was used to evaluate the impact of input variables on predefined responses or quality attributes of the microspheres. The percent degradation of rifampicin following 12 h dissolution testing in 0.1 M HCl pH 1.2 in the presence of isoniazid gastric-resistant sustained-release microspheres was only 4.44%. These results indicate that the degradation of rifampicin in the presence of isoniazid in acidic media can be reduced by encapsulation of both active pharmaceutical ingredients to ensure release in different segments of the gastrointestinal tract, potentially improving the bioavailability of rifampicin. Full article
(This article belongs to the Special Issue Encapsulation Techniques Applied to Pharmaceutics)
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Review

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23 pages, 851 KiB  
Review
Transfersomes: A Promising Nanoencapsulation Technique for Transdermal Drug Delivery
by Shakthi Apsara Thejani Opatha, Varin Titapiwatanakun and Romchat Chutoprapat
Pharmaceutics 2020, 12(9), 855; https://doi.org/10.3390/pharmaceutics12090855 - 09 Sep 2020
Cited by 221 | Viewed by 13805
Abstract
Transdermal delivery systems have gained much interest in recent years owing to their advantages compared to conventional oral and parenteral delivery systems. They are noninvasive and self-administered delivery systems that can improve patient compliance and provide a controlled release of the therapeutic agents. [...] Read more.
Transdermal delivery systems have gained much interest in recent years owing to their advantages compared to conventional oral and parenteral delivery systems. They are noninvasive and self-administered delivery systems that can improve patient compliance and provide a controlled release of the therapeutic agents. The greatest challenge of transdermal delivery systems is the barrier function of the skin’s outermost layer. Molecules with molecular weights greater than 500 Da and ionized compounds generally do not pass through the skin. Therefore, only a limited number of drugs are capable of being administered by this route. Encapsulating the drugs in transfersomes are one of the potential approaches to overcome this problem. They have a bilayered structure that facilitates the encapsulation of lipophilic and hydrophilic, as well as amphiphilic, drug with higher permeation efficiencies compared to conventional liposomes. Transfersomes are elastic in nature, which can deform and squeeze themselves as an intact vesicle through narrow pores that are significantly smaller than its size. This review aims to describe the concept of transfersomes, the mechanism of action, different methods of preparation and characterization and factors affecting the properties of transfersomes, along with their recent applications in the transdermal administration of drugs. Full article
(This article belongs to the Special Issue Encapsulation Techniques Applied to Pharmaceutics)
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