Reverse-phase Evaporation Method Research Articles

An Overview of Transferosomal Technology

Abstract: Ever since the invention of liposomes by Bangham in 1963, researchers have been fascinated by the vesicular carriers. Liposomes and niosomes have been used extensively by researchers for various routes such as oral and nasal. However, lately, it has been understood that traditional liposomes are not very significant when it comes to penetration. The use of nanovesicles in transdermal drug delivery systems has been enhanced exponentially ever since the discovery of ultra- deformable liposomes known as transfersomes or transferosomes. Transferosomes have numerous advantages, such as biocompatibility, biodegradability, flexibility, and deformability, so that they can pass through narrow constrictions. They have good entrapment efficiency and can act as a depot to sustain the release of drugs. The methods of preparation include the rotary film evaporation method, reverse phase evaporation method, vortexing sonication method, ethanol injection method, and freeze-thaw method. Transfersomes are characterized by particle size, zeta potential, polydispersity index, surface morphology, and encapsulation efficiency. Transferosomes have been successfully exploited for the enhancement of efficacy of many drugs like Hydroquinone, Itraconazole, Ivabradine, lornoxicam, minoxidil etc., via transdermal and nasal routes. The technology is easy to scale up. Consequently, it can be inferred that transfersomes are the future of transdermal drug delivery systems.

Nanoliposomes Encapsulated Rapamycin/Resveratrol to Induce Apoptosis and Ferroptosis for Enhanced Colorectal Cancer Therapy

Objectives: Monotherapy is often ineffective for treating colorectal cancer. In this study, we developed PEG-modified liposomes loaded with rapamycin (Rapa) and resveratrol (Res) (Rapa/Res liposomes, or RRL) to investigate their therapeutic potential in colorectal cancer.Methods: RRL were constructed using the reversed-phase evaporation method. We assessed the cytotoxicity, apoptosis, and ferroptotic effects of RRL on HCT116 colorectal cancer cells. The anti-tumor efficacy of RRL was evaluated in HCT116 xenograft mice.Results: RRL had a particle size of 86.67 ± 1.10 nm and a zeta potential of -33.13 ± 0.49 mV. The coloaded formulation demonstrated satisfactory performance both in vitro and in vivo, resulting in increased cytotoxicity to HCT116 colorectal cancer cells and significant suppression of HCT116 xenografts tumor growth. Mechanically, RRL significantly increased the apoptosis rate of HCT116 cells, induced ROS accumulation in tumor cells, and effectively downregulated the expression of the ferroptosis-associated proteins GPX4 and SLC7A11, demonstrating its superior efficacy compared to that of Rapa liposomes (Rapa/Lps) or Res liposomes (Res/Lps) alone.Conclusion: Coloading Rapa and Res into liposomes to promote apoptosis and ferroptosis in tumor cells represents a promising strategy for the treatment of colorectal cancer.

Exploring the Antitumor Efficacy of PEGylated Liposomes Loaded with Licorice Extract for Cancer Therapy.

Glycyrrhizic Acid (GA), a compound derived from licorice, has exhibited promising anticancer properties against several cancer types, including Prostate Cancer (PCa) and Gastric Cancer (GCa). This study has introduced a novel approach involving the encapsulation of GA and Licorice extract (Lic) into Polyethylene Glycol Liposomes (PEG-Lip) and assessed their efficacy against AGS (human gastric cancer) and PC-3 (human prostate cancer) cells, marking the first report of this endeavor. We synthesized GA-loaded PEG-Lip (GA PEG-Lip) and Lic-loaded PEG-Lip (Lic PEG-Lip) through the reverse-phase evaporation method. Characterization of these liposomal formulations revealed their size, drug encapsulation, and loading efficiencies to be 110 ± 2.05 nm, 117 ± 1.24 nm; 61 ± 0.81%, 34 ± 0.47%; and 8 ± 0.41% and 4.6 ± 0.21%, respectively. Importantly, the process has retained the chemical structure of both GA and Lic. Furthermore, GA and Lic have been released from the PEG-Lip formulations in a controlled manner. In our experiments, both nanoformulations exhibited enhanced cytotoxic effects against AGS and PC-3 cells. Notably, GA PEG-Lip outperformed Lic PEG-Lip, reducing the viability of PC-3 and AGS cells by 12.5% and 15.9%, respectively. These results have been corroborated by apoptosis assays, which have demonstrated GA PEG-Lip and Lic PEG-Lip to induce stronger apoptotic effects compared to free GA and Lic on both PC-3 and AGS cells. This study has underscored the potential of encapsulating GA and Lic in PEG-Lip as a promising strategy to augment their anticancer efficacy against prostate and gastric cancers.

Abstract 5750: Development of prostate specific membrane antigen-targeted liposomal zinc for the treatment of prostate cancer

Abstract Introduction: Treatment choices for early-stage prostate cancer include mostly watchful waiting, radical prostatectomy, or radiation therapy, whereas for advanced cases hormone therapy followed by chemo/radiotherapy are the preferred options, despite their notable side effects. There is a need for more effective therapy with lower side effects, especially for advanced scenarios. Unlike normal epithelial prostate cells, cancerous ones show reduced zinc (Zn) levels due to ZIP1 zinc transporter downregulation. Zn deficiency allows m-aconitase to remain active, making prostate cancer cells energy efficient and grow. High levels of Zn are needed to inhibit m-aconitase, the enzyme responsible for the first reaction in the Krebs cycle. This study aims to induce energy starvation and cell death of prostate cancer cells by inhibiting m-aconitase using the prostate-specific membrane antigen (PSMA)-targeting liposomal zinc. Methods: Liposomes were prepared by standard reverse phase evaporation method with DSPC, Cholesterol and DSPE-mPEG(2000) lipids. Zinc chloride was used to load Zn+2 into liposome following passive loading method. PSMA-expressing (PC3-PIP) and PSMA-null (PC3-LUC) human prostate cancer cells were used for in vitro studies. In the cell uptake study, cells were incubated with Dil-dye labeled liposomes for 2 hours before analyzing them by microscopy and flow cytometry. For the uptake inhibition study, cells were pre-incubated with PSMA-specific peptide for 2 hours before incubation with liposomes. Cytotoxicity studies were performed with PSMA-targeting Zn-loaded liposomes in PC3-PIP cells. Results: We conjugated the PSMA-specific peptide and control peptide (ASP3) with DSPE-PEG(3400)-NHS, and used them at various amounts (1 to 4 mol% of total lipid) to prepare Zn-loaded PSMA-targeting liposomes (TL) and control liposomes (CL), respectively. The average hydrodynamic diameter of all the liposomes was 120 to 130 nm, and zeta potential ranged from -16 to -12 mV. The encapsulation efficiency and loading capacity of Zn+2 were 0.6% and 8.5%, respectively. Cellular uptake studies showed a higher accumulation of PSMA-targeting liposome (TL) compared to non-targeting liposome (CL) in PSMA-expressing PC3 cells, whereas both liposomes showed low uptake in PSMA non-expressing cell. Furthermore, pre-treatment of PSMA-expressing cells with PSMA-specific peptide reduced the uptake of TL, indicating that the uptake of TL liposome is PSMA dependent. Finally, cytotoxicity studies showed that Zn-loaded TL, induces cell death in the PSMA-expressing cells. Overall, we developed PSMA-targeting Zn-containing liposomes that selectively target and kill PSMA-expressing prostate cancer cells. Future work includes testing the effect of Zn-loaded TL on m-aconitase activity and testing of in vivo efficacy of the formulation in prostate cancer models. Citation Format: Sujan K. Mondal, Alexander L. Klibanov, Anna Moore. Development of prostate specific membrane antigen-targeted liposomal zinc for the treatment of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5750.

A novel strategy for partial purification of alkane hydroxylase from P. chrysogenum SNP5 through reconstituting its native membrane into liposome

Integral proteins or enzymes are still challenging to purify into their native state because of their need for an amphipathic environment and cofactors. Alkane hydroxylase (AlkB) is a membrane-bound enzyme that catalyzes the hydroxylation of a range of alkanes that have a broad spectrum of applications. In the current study, a novel approach has been explored for partial purification of alkane hydroxylase (AlkB) in its native state through restructuring the lipid bilayer of Penicilliumchrysogenum SNP5 into a liposome to extend the native and protective environment to AlkB enzyme. Three different methods i.e., reverse-phase evaporation method (RPEM), detergent-based method (DBM), and ethanol injection method (EIM) have been used for reconstituting its native membrane into liposome. On characterizing liposomes through fluorescence imaging, AFM, and particle size analysis, the reverse-phase evaporation method gave the best results based on the size distribution (i.e., 100–300 nm), the morphology of liposomes, and maximum AlkB specific activity (i.e., 140.68 U/mg). The maximum reconstitution efficiency of 29.48% was observed in RPEM followed by 17.3% in DBM and 12.3% in EIM. On the characterization of the purified AlkB, the molecular weight was measured of 44.6 KDa and the thermostability of liposomes synthesized with the RPEM method was obtained maximum at 55 °C. This approach may open a new strategy for the purification of integral enzymes/proteins in their native state in the field of protein purification and its applications in diversified industries.

LIPOSOMAL DELIVERY OF IMMUNOMODULATORY ANTIGEN OF B. MALAYI: ISOLATION, PREPARATION, CHARACTERIZATION, AND IMMUNE RESPONSES ASSESSMENT

Objective: The present study was aimed on developing and characterizing liposomal delivery system loaded with antigen of filaria parasite Brugia malayi extracted protein for assessment of humoral immune responses of antigen. Methods: Liposomes were prepared by reverse-phase evaporation method with slight modification using molar ratio of Soya PC: PE:Cholesterol in different molar concentrations. Results: The levels of F6 specific immunoglobulin (Ig) G1, IgG2a and IgG2b antibodies were found to be elevated in immunized animals over non-immunized controls. Analysis of IgG-subclasses revealed that all the subclasses at (1:25dilution) increased several folds over the controls with IgG1 showing the greatest increase (25.0-fold) followed by IgG2b (3.0-fold). Antibodies titers showed the many fold increment of titers on liposomized antigen groups (Gr.I; without booster dose and Gr.IV; with booster dose). IgG showed about 2.2 fold increment in Gr.IV than control group (Gr.V). IgG1 after booster dose showed about 25-fold increment followed by IgG2b than IgG2a. Conclusion: These results suggest that the liposomal antigen delivery system shows 25-fold IG-G responses in comparison to plain administrated antigen.

Liposome Encapsulation of the Palmitoyl-KTTKS Peptide: Structural and Functional Characterization.

In this study, the amphiphilic N-palmitoyl-KTTKS peptide was integrated in the bilayer of egg-derived phosphatidylcholine (PC) vesicles using two different preparation methods, namely thin-film evaporation (TLE) and reverse-phase evaporation (REV). Both the REV and TLE methods allowed for the formation of homogeneous liposome dispersions (PdI < 0.20) with mean hydrodynamic diameters of <100 nm and <200 nm, respectively, a net negative surface charge and a percentage of structured phospholipids higher than 90%. The inclusion of the amphiphilic N-palmitoyl-KTTKS peptide within phospholipid-based vesicles could improve peptide stability and skin delivery. Therefore, the obtained liposomes were evaluated via experiments assessing the synthesis of collagen and the ECM in 3T3-NIH fibroblasts. The obtained results showed that, when delivered with PC liposomes, pal-KTTKS stimulated collagen production more than free pentapeptide and 1 mM ascorbic acid, used as a positive control.

Liposomes Enhance the Immunological Activity of Polygonatum Cyrtonema Hua Polysaccharides

Poor stability and difficult uptake of natural polysaccharides have been the main problems in their application. The purpose of this study was to optimize the preparation conditions of Polygonatum cyrtonema Hua polysaccharides liposomes (PCPL) and to investigate the immune enhancement activity of PCPL in vitro and in vivo, with a view to discovering new ways of natural polysaccharide application. The optimal preparation conditions of PCPL were as follows: the adding amount of Tween 80 of 0.5 %, the ultrasound time of 2 min and the ultrasound times of once. Under these conditions, the entrapment efficiency, drug loading rate and particle size of PCPL were 38.033 %±0.050, 2.172 %±0.003 and 146 nm, which indicated that PCPL with small particle size could be prepared by the reverse-phase evaporation method. Furthermore, PCPL promoted proliferation, phagocytosis, and secretion of nitric oxide and related cytokines in RAW264.7 cells. Moreover, PCPL improved spleen and thymus indices, increased the number or proportion of red blood cells, platelets, and lymphocytes in the blood, and ameliorated spleen and thymus atrophy in immunosuppressed mice. This study provides a new idea for applying Polygonatum cyrtonema Hua polysaccharides (PCP) and references for studying other polysaccharides.

Nattokinase Encapsulated Nanomedicine for Targeted Thrombolysis: Development, Improved in Vivo Thrombolytic Effects, and Ultrasound/Photoacoustic Imaging.

Nattokinase (NK), a potent thrombolytic enzyme that dissolves blood clots, is highly used in the treatment of cardiovascular disorders. However, its effective delivery remains demanding because of stability and bioavailability problems owing to its high molecular weight and proteineous nature. In this research, we have developed novel NK-loaded nontargeted liposomes (NK-LS) and targeted liposomes (RGD-NK-LS and AM-NK-LS) by the reverse phase evaporation method. The physiochemical characterizations (particle size, polydispersity index, zeta potential, and morphology) were performed by a Zetasizer, SEM, TEM, and AFM. The Bradford assay and XPS analysis confirmed the successful surface conjugation of the targeting ligands. Platelet interaction studies by CLSM, photon imager optima, and flow cytometry showed significantly higher (P < 0.05) platelet binding affinity of targeted liposomes. In vitro evaluations were performed using human blood and a fibrinolysis study by CLSM imaging demonstrating the potent antithrombotic efficacy of AM-NK-LS. Furthermore, bleeding and clotting time studies revealed that the targeted liposomes were free from any bleeding complications. Moreover, the in vivo FeCl3 model on Sprague-Dawley (SD) rats using a Doppler flow meter and ultrasound/photoacoustic imaging indicated the increased % thrombolysis and potent affinity of targeted liposomes toward the thrombus site. Additionally, in vitro hemocompatibility and histopathology studies demonstrated the safety and biocompatibility of the nanoformulations.

Bilosomes as Soft Nanovesicular Carriers for Ropinirole Hydrochloride: Preparation and In- vitro Characterization

Bilosomes are nanovesicular carriers that contain bile salts and non-ionic surfactants in a bilayer with cholesterol. These are more ultra-deformable, elastic, and flexible than other nanovesicular carrier.Ropinirole hydrochloride (RH) is a non-ergot dopamine D2-agonist. It is used to manage Parkinson's disease and to minimize "on-off" variations in levodopa responsiveness. The oral bioavailability is about 50% due to it being extensively metabolized in the liver, with an elimination half-life of about 6 h.The aim of this study was to enhance oral drug delivery and provide the sustained release of RH by preparing it as soft nanovesicular carriers (bilosomes).Eight formulas of RH bilosomes were prepared by a reverse-phase evaporation method using mixed surfactant (span®60: tween®60 at 1:2 ratio), cholesterol and sodium deoxycholate as bile salt.All formulas were evaluated for their drug content, entrapment efficiency, vesicle size, polydispersity index, zeta potential, drug release, transmission electron microscopy and fourier transform infrared spectroscopy.Results showed all prepared RH bilosomes were in nano-range with vesicle size ranging (from 124.40±10.60 to 294.60±11.50) nm, Zeta potential ranged (from -16.955±7.372 to -23.22±0.880) mV and with entrapment efficiency % ranged (from 57.30±6.48% to 77.77±3.78%).&#x0D; The best formula F5 showed vesicle size (160.60±15.82) nm, Zeta potential (-20.75±0.930) mV, and entrapment efficiency %(77.77±3.78%) with 84.39% in-vitro release of RH after 24 h.It is concluded that bilosomes are good nanovesicular carriers for enhancing oral drug delivery and providing the sustained release of RH and all that may enhance oral bioavailability for RH.

Formulation and Evaluation of Niosomal Gel for Treatment of Acne

A skin disease, like acne, is very common and normally happens to everyone at least once in their lifetime. The structure of the stratum corneum is often compared with a brick wall, with corneocytes surrounded by the mortar of the intercellular lipid lamellae. Acne vulgaris is a chronic inflammatory dermatosis which is notable for open and/or closed comedones (blackheads and whiteheads), and inflammatory lesions including papules, pustules, or nodules. It is a disorder of sebaceous follicles which are special pilosebaceous units located on the face, chest, and back. Skin is one of the most readily available organs on human body for topical management and is the major route of topical drug delivery system. Topical drug administration is a localized drug delivery system everywhere in the body during ophthalmic, vaginal, rectal and skin as topical routes. SA niosomes gel delivery system (SANG1 to SANG5) as a dispersed system, which consists of small droplets and well distributed in to immiscible vehicle. Niosome salicylic acid was prepared by Reverse phase evaporation method using cholesterol and span 80 and tween 20. Niosome were evaluated for vesicle shape, size determination, Entrapment efficiency and in-vitro drug release study. The result concluded that SANG5 was best formulation with Carbopol 940 (2g), PVP, nutmeg oil base. The drug release profile and release kinetics are two important characteristics of the dosage forms, which play an important role for describing dissolution profile of dosage form.&#x0D; Keywords: Topical drug delivery, Acne vulgaris, Niosomes, Gel, Carbopol 940, nutmeg oil

Ultrasound-targeted semaglutide-loaded PEG-nanoliposomes microbubble destruction protects diabetic cardiomyopathy by activating PI3K/Akt/Nrf2 signaling pathway

ObjectiveTo investigate the ameliorative effect of Semaglutide-loaded PEG-nanoliposomes (Sem-PEG-lips) combined with ultrasound-targeted microbubble destruction (UTMD) on streptozotocin (STZ)-induced diabetic cardiomyopathy (DCM) in rodents and its potential mechanisms. MethodsSem-PEG-lips were prepared by the reverse phase evaporation method. Fifty STZ-induced diabetic rats were randomly divided into DCM model group, Sem or Sem-PEG-lips alone treatment group, UTMD + Sem group and UTMD + Sem-PEG-lips group (n = 10), respectively, and used the healthy rats as normal control. During the 12-week intervention, the weight and blood glucose levels of all rats were recorded. Myocardial injury and fibrosis were observed by using H&E and Masson staining. The activity of antioxidant enzymes and the expression levels of oxidative stress-related signaling pathway markers in myocardial tissues were measured by ELISA and western blotting method, respectively. ResultsCompared with DCM rats, the body weight and blood glucose levels of those in the UTMD + Sem-PEG-lips group were significantly increased and decreased, respectively (both p < 0.05). The results of H&E and Masson staining showed that myocardial fibrosis and apoptosis were both significantly improved in combination group (both p < 0.001). Further results of ELISA and Western blot analysis showed that the activity of antioxidant enzymes in ones received combination therapy were significantly higher than that in DCM model group (all p < 0.001), and the expression of PI3K/Akt/Nrf2 signaling pathway related proteins were significantly up-regulated (all p < 0.001), and all these changes were reversed by the treatment of PI3K inhibitor. results ConclusionUTMD combined Sem-PEG-lips can reduce the oxidative stress of myocardial tissue in DCM rats by activating PI3K/Akt/Nrf2 signaling pathway, thereby improving diabetic myocardial injury.

Effects of Different Types of Bile Salts on the Physical Properties of Ropinirole-Loaded

Background: Bilosomes are vesicular nanocarriers that contain bile salts, making them more flexible and resistant to degradation in the gastrointestinal tract. Objective: To evaluate the effect of two bile salts on the physical properties and stability of the ropinirole-loading bilosome. Methods: Sixteen bilosomal formulations were prepared by a reverse-phase evaporation method. Each formula includes a mixture of non-ionic surfactants (Span®60 and Tween®60), along with cholesterol and bile salts (either sodium taurocholate (STC) or sodium glycocholate (SGC). The characteristics of the bilosomal formulations (drug content, entrapment efficiency, vesicle size, polydispersity index, zeta potential, in-vitro drug release, and Fourier transform infrared spectroscopy) were evaluated. Results: The entrapment efficiency of ropinirole was reduced by using sodium glycocholate instead of sodium taurocholate. The vesicle size and zeta potential were also affected by the type of bile salt and its amount. Drug release profiles were sustained, indicating a good entrapment of ropinirole. The STC-containing bilosomes are more stable than the SGC-containing bilosomes. Bilosomal formula F5 showed the highest entrapment efficiency (64.82%), suitable vesicle size (179.8 nm), zeta potential (-9.162 mV), polydispersity index (0.5116), and in vitro drug release (62.33%) after 24 hr. Conclusion: Sodium taurocholate was more suitable for the preparation of ropinirole-loading bilosomes, with more stability of bilosomes in bile salt solution.

Profiling and Evaluation of the Effect of Guarana-Loaded Liposomes on Different Skin Cell Lines: An In Vitro Study

The objective of this study was to analyze the in vitro stability and toxicity of liposomes containing guarana in skin cell lines. The liposomes were produced by the reverse phase evaporation method containing 1 mg/mL guarana. The stability of the liposomes was evaluated by physical-chemical parameters for up to 90 days using three different storage conditions. The cytotoxicity of guarana (GL), liposomes (B-Lip), and guarana-loaded liposomes (G-Lip) was evaluated on spontaneously immortalized human keratinocyte cell lines (HaCaT), murine Swiss albino fibroblasts (3T3), and human fibroblasts (1BR.3.G). The evaluation was performed using cellular viability analysis. The techniques used were 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red capturing (NRU), and the analyses were conducted after 24, 48, and 72 h of exposure of these cells to the different treatments. The G-Lip exhibited physical-chemical stability for 60 days when the samples were stored in a refrigerator. The GL, B-Lip, and G-Lip demonstrated low cytotoxicity in the three different cell cultures tested since a small reduction in cell viability was only observed at the highest concentrations. In addition, greater cell damage was observed for B-Lip; however, guarana protected the cells from this damage. Thus, G-Lip structures can be considered promising systems for topical applications.

Preparation, Characterization and Application of Niosomes for the Delivery of Herbal Bioactive Agents: A Mini Review

The demands of herbal products including Nutraceuticals, cosmetics and drugs increased tremendously globally in recent times. Herbal compounds offer limited toxicity, high biocompatibility with numerous health benefits. The herbal drugs show many health benefits due to their presence of bioactive compounds in it. However, bioactive compounds suffer due to their poor solubility, poor bioavailability and stability. Niosomes, a non-ionic surfactant vesicle, can be a promising aspect to deliver the bioactive compound to enhance the bioavailability and stability. Niosomes have many advantages as it enables encapsulation of either hydrophilic and hydrophobic compounds. Preparation methods of niosomes are also simple and inexpensive. Moreover, encapsulating bioactive compounds in niosome not only improve the bioavailability but also enable it for sustained release or controlled release drug delivery. The review highlights various methods for niosome preparation, including thin-film hydration, reverse-phase evaporation, ether injection, microfluidization and bubble methods along with their advantages and disadvantages. Additionally, the characterization techniques, such as size determination, zeta potential measurement, and morphological evaluation, are also discussed.

Formulation and Characterization of Novel Transfersomes Gel for Enhance TDDS of Losartan Potassium

A transferosome is the first generation of an elastic liposome prepared from phospholipids and edge activators. An edge activator is often a single-chain surfactant with a high radius of curvature that destabilizes the lipid bilayers of vesicles and increases the deformability of the bilayers, thereby making the vehicle ultra-deformable. Losartan potassium is an orally active angiotensin-II receptor antagonist used in the treatment of hypertension due to mainly blockade of AT1 receptor. It is freely soluble in water, slightly soluble in acetonitrile, and soluble in isopropyl alcohol. The aim of the present study was to investigate the potential of transfersomal gel formulations for transdermal delivery of losartan potassium by reverse phase evaporation method. Characterization of transfersomes gel performed by vesicle size, pH measurements, drug content, entrapment efficiency, in vitro drug diffusion study, spreadability and stability study. In the formulations pH is found to be around 6.8 to 6.9, pH is found in the range of 6 which is compatible with skin. In the formulations spreadability is found to be around 6.75 to 10.11 g m cm/sec. The prepared gel containing losartan potassium-loaded transfersomal formulation was optimized and can be use for topical preparation. The results were obtained which showed that transfersomal gel was a promising candidate for transdermal delivery with targeted and prolonged release of a drug. It also enhances skin permeation of many drugs.&#x0D; Keywords: Transferosome gel, Losartan potassium, Antihypertensives, Reverse phase evaporation method

Transfersomes: An Innovative Vesicular Carrier for Boosted Transdermal Delivery System

One may find difficulties with oral and parenteral drug delivery systems in a routine of clinical practice because they do not have sufficient compliance and bioavailability for patients. So, nowadays transdermal route is a greater area of interest of pharmaceutical research for delivering drug. But skin is the most challenging area to cross in transdermal delivery of drug as the stratum corneum &amp; the outer layer of the skin have tight intracellular junctions. Researchers have developed various approaches like micro needle, sonophoresis, electrophoresis, and iontophoresis etc to overcome those complications for the transdermal delivery of drugs. Chemical permeation enhancers are needed in vesicular drug delivery system such as niosomes, liposomes, elastic liposomes (transfersomes and ethosomes) to improve their penetration property. Transferosomes can be prepared by a number of methods like vortexing, sonication method, freeze–thaw method, ethanol injection method, Reverse-phase evaporation method, etc. Transfersomes can carry wide ranges of drugs having a wide range of solubility within it as they are constructed of hydrophobic as well as hydrophilic moieties. The main property of transferosome is deformability. This flexible nature of the vesicle membrane helps transfersome to go across the narrow pores with a maximum amount of drugs present within it. They have high deformable capacity which exhibits advanced penetration capability of intact vesicles. Both high and low molecular weight drugs like albumin, insulin, corticosteroids, sex hormones, anesthetic, anticancer, analgesic can be fused within transfersome.

Preparation and evaluation of niosomal chitosan-based in situ gel formulation for direct nose-to-brain methotrexate delivery

Achieving effective treatments for various brain disorders due to the blood-brain barrier existence and the brain's complex structure has become a challenging goal. To overcome these challenges, one of the non-invasive strategies aimed at direct brain drug delivery is the use of the intranasal route. Novel drug delivery systems can be used to overcome the limitations in this administration route. This study suggested niosomal methotrexate (MTX) in situ gel formulation, which could be a suitable candidate for drug delivery to the brain. Here, niosomal MTX was prepared by a modified reverse-phase evaporation method, optimized with the aid of the design expert® software, and characterized. Optimum niosomal MTX with particle size, zeta potential, and entrapment efficiency (EE%), equal to 130.5 nm, −38.5 mV, and 91.39 %, respectively, were added into the temperature-sensitive in situ gel formulation composed of chitosan and Poloxamer 407. This study demonstrates that the simultaneous use of niosome and in situ gel formulations causes long-term persistence in the nasal cavity and helps us to have a more controlled drug release system with higher brain concentration, lower plasma concentration, higher Kp, and lower side effects compared to the free drug (MTX solution), MTX-gel (MTX-loaded in situ gel), and niosomal MTX formulations.

Carboplatin Niosomal Nanoplatform for Potentiated Chemotherapy

This study aimed to characterize a stable nano-niosome formulation, which could reduce the adverse effects of carboplatin (CB) and improve its therapeutic efficacy in the treatment of breast cancer. For this purpose, CB-loaded polyethylene glycol (PEG)ylated niosome nanoparticles (PEG-NS-CB) were synthesized using the reverse-phase evaporation method. PEG-NS-CB (226.0 ± 10.6 nm) could release CB in a controlled manner and, compared to CB and CB-loaded non-PEGylated niosome (NS-CB), caused higher cytotoxicity effects against mouse breast cancer 4T1 cells (IC50: 83.4, 26.6, and 22.5 µM for CB, NS-CB, and PEG-NS-CB, respectively). Also, PEG-NS-CB demonstrated higher stability, in which its profile of drug release, cytotoxicity, and LE% did not change significantly three months after preparation compared to those at the production time. In addition, the in vivo results demonstrated that PEG-NS-CB caused higher therapeutic (the number of alive mice: 12, 15, and 17 out of 20 in CB, NS-CB, and PEG-NS-CB receiver groups, respectively) and less toxicity effects (weight loss of 17, 12.5, and 10% in CB, NS-CB, and PEG-NS-CB receiver groups, respectively), compared to NS-CB and CB in breast cancer-bearing mice. Overall, the results of this study suggest that PEG-NS-CB could be a promising formulation for the treatment of breast cancer.

In Vitro Nephrotoxicity and Permeation of Vancomycin Hydrochloride Loaded Liposomes.

Drugs can be toxic to the fetus depending on the amount that permeates across the maternal–fetal barrier. One way to limit the amount which penetrates this barrier is to increase the molecular size of the drug. In this study, we have achieved this by encapsulating our model antibiotic (vancomycin hydrochloride, a known nephrotoxic agent) in liposomes. PEGylated and non-PEGylated liposomes encapsulating vancomycin hydrochloride were prepared using two different methods: thin-film hydration followed by the freeze–thaw method and the reverse-phase evaporation method. These liposomes were characterized by their hydrodynamic size and zeta potential measurements, CryoTEM microscopy, loading and encapsulation efficiency studies, in vitro release measurements and in vitro cytotoxicity assays using NRK-52 E rat kidney cells. We also determined the in vitro permeability of these liposomes across the human placental cell and dog kidney cell barriers. Vancomycin hydrochloride-loaded PEGylated liposomes (VHCL-lipo) of a size less than 200 nm were prepared. The VHCL-lipo were found to have the faster release of vancomycin hydrochloride and resulted in greater viability of NRK-52E cells. In vitro, the VHCL-lipo permeated the human placental cell and dog kidney cell barriers to a lesser extent than the free vancomycin hydrochloride. The data suggest a reduction in nephrotoxicity and permeability of vancomycin hydrochloride after encapsulation in PEGylated liposomes.