Ethanol Injection Method Research Articles

Simvastatin-Loaded PEGylated Solid Lipid Nanoparticles: Lipid Functionalization to Improve Blood Circulation

The aim of the present work was to formulate simvastatin-loaded PEGylated solid lipid nanoparticles (PEG-SLNs) for prolonging blood circulation. Plain solid lipid nanoparticles (P-SLNs) were prepared by ethanol injection method. Prepared P-SLNs were PEGylated using carbodiimide chemistry by coupling the amine group of bis-amine PEG with the carboxyl group of the phosphatidylcholine present on the surface of previously formed drug-loaded P-SLNs in the presence of 1-ethyl-3(3-dimethylaminopropyl) carbodiimide (EDC). The success of the pegylation of P-SLNs was confirmed by the IR spectra of P-SLNs and PEG-SLNs. The average particle size and zeta potential for P-SLNs and PEG-SLNs were found to be 322.3 ± 3.71 nm; − 32.7 ± 0.15 and 351.6 ± 1.23 nm; − 10.6 ± 0.79, respectively. DSC curves and XRD pattern confirmed the homogenous dispersion of simvastatin and concluding the presence of simvastatin in an amorphous state in both nanoparticle formulations. A biphasic in vitro drug release pattern was found with both the nanoparticles formulations, P-SLNs shows a drug release of 96.02 ± 2.41% within 48 h, while 91.89 ± 1.72% drug was released from PEG-SLNs within 72 h. PEG-SLNs were found to be less hemolytic toxic as compared to P-SLNs. Prepared PEG-SLNs were found to be long-circulating, with low elimination and better serum profiles.

Formulation and Evaluation of Lyophilized Nanocochleates of Paclitaxel – For Cancer Chemotherapy

The nanocochleates are mainly prepared from the liposomes of active pharmaceutical ingredients (APIs) with the help of inactive ingredients like phosphatidylserine (PS) and calcium. The PS shows a considerable binding affinity towards calcium mainly due to the calcium’s tendency to lose part of its hydration shell and to displace water upon complexation. Due to neutralization of the electrostatic charge, calcium causes aggregation & fusion of liposomes composed PS with each other. It has been reported that ca++ has an affinity to form a more tightly packed & highly ordered and less hydrated structure than mg++ with phosphatidylserine, even at a much lower concentration. It is well documented that ca++ plays a vital role in natural membrane fusion phenomena while other cations are ineffective in most such systems. The stability of Nano-cochleate can be increased by doing freeze-drying of finished product which in turn provides a longer shelf life to the product at, where solution form is most unstable. Based on various literature survey and laboratory work, ‘The Ethanol Injection Method’ was selected for the preparation of Nanoliposomes followed by Nanocochleates. For this study; Paclitaxel was selected as an Active Pharmaceutical Ingredient (API) to formulate Phospholipid based Nanocochleate. The developed Nanocochleates exhibited higher encapsulation efficiency and controlled release of Paclitaxel. This technology may bring about a reduction in dose as well as cost and increase patient compliance. These Nanocochleates could therefore advantageously be employed to improve anticancer activity of Paclitaxel and an alternative to present intravenous administration. From the present study, it can be concluded that the developed Nanocochleates exhibited higher encapsulation efficiency and controlled release of Paclitaxel which may prove to be a suitable & potential candidate for healing a Cancer at a lower concentration.

Preparation of Berberin Proliposomes by Film Deposition on Carrier Surface Method

This study aims to formulate berberin (BBR) proliposomes by film-deposition on carrier surface to increase BBR’s solubility and permeability through biological membranes. Proliposomes were hydrated in water to form BBR liposomes for determining the size and distribution of the vesicles. Differential thermal analysis was used to evaluate the BBR proliposomes. The study results show that berberin proliposomes prepared with hydrogenated soy phosphatidylcholine: cholesterol: berberin with a molar ratio of 9:1:6 using sorbitol as carrier with a weight ratio to lipid of 10:1. The obtained BBR proliposomes in the form of a dry yellowish powder were hydrated in water to form BBR liposomes with an average diameter of about 8.41μm. The results of the differential thermal analysis show that BBR was dispersed in molecular form into proliposomes. 
 Keywords:
 Berberin, proliposomes, sorbitol, film-deposition on the carrier method.
 References
 [1] J. Plessis, C. Ramachandran, N. Weiner, D.G Müller, The influence of lipid composition and lamellarity of liposomes on the physical stability of liposomes upon storage, International Journal of Pharmaceutics, 2 (1996) 273-278. https://doi.org/10.1016/0378-5173(95)04281-4[2] A.V. Yadav, M.S. Murthy, Stability Aspects of Liposomes, Indian Journal of Pharmaceutical Education and Research 24 (2011) 402413 – 43. [3] V. Nekkanti, N. Venkatesan, G.V. Betageri, Proliposomes for Oral Delivery: Progress and Challenges, Current Pharmaceutical Biotechnology, 16(2015) 303-312. 10.2174/1389201016666150118134256[4] M. Khayam, S. Umar, Berberine nanoparticles with enhanced in vitro bioavailability: characterization and antimicrobial activity, Drug Design, Development and Therapy, 12 (2018) 303-312. https://doi.org/10.2147/DDDT.S156123[5] S.J. Jia, G.Y. Ningning, L. Zhang, Y. Zhao, Release-controlled curcumin proliposome produced by ultrasound-assisted supercritical antisolvent method, Journal of Supercritical Fluids, 113 (2016) 150-157. https://doi.org/10.1016/j.supflu.2016.03.026.[6] K.G.B. Sharan, R.V. Prabhakar, Formulation, evaluation, and pharmacokinetics of isradipine proliposomes for oral delivery, Journal of liposome research, 4(2012) 285-294. https://doi.org/10.3109/08982104.2012.697067.[7] Q. Fu, H.L. Fu, L. Huan, Preparation of cefquinome sulfate proliposome and its pharmacokinetics in rabbit, Iranian journal of pharmaceutical research, 4 (2013) 611-21. [8] T.T. H. Yen, T.T. Loan, D.T. Thuan, P.T.M. Hue, Preparation of berberin liposomes by ethanol injection method, Pharmaceutical journal, 59 (2019) 54-58 (in Vietnamese). [9] P. Elahehnaz, R. Marzieh, K. Maryam, Design and development of vitamin C-encapsulated proliposome with improved in-vitro and ex-vivo antioxidant efficacy, Journal of microemulsion 3(2018) 301 – 311. https://doi.org/10.1080/02652048.2018.1477845[10] I. Khan, S. Yousaf, S. Subramanian, Proliposome tablets manufactured using a slurry-driven lipid-enriched powders: Development, characterization and stability evaluation, J Int Pharm 1-2 (2018) 250 – 262. doi: 10.1016/j.ijpharm.2017.12.049[11] N.I. Payne, P. Timmins, V.A. Cheryl, Proliposomes: A Novel Solution to an Old Problem, Journal of Pharmaceutical Sciences 4 (1986) 325-329. https://doi.org/10.1002/jps.2600750402.
 
 
 

Antioxidant activity and absorption of cyanidin-3-O-glucoside liposomes in GES-1 cells in vitro.

The use of anthocyanins are limited by their chemical properties. Recent evidence suggests Cyanidin-3-O-glucoside (C3G) liposomes via the ethanol injection method exhibit improved stability. In the current study, the characterization and cell absorption of C3G liposomes were explored via transmission electron microscopy and flow cytometry. The internalization of the C3G liposomes across the gastric epithelial cell monolayer (GES-1 cells) were investigated. Results showed that the particle size and encapsulation efficiency were 234±9.35nm and 75.0% ± 0.001, respectively. The total antioxidant capacity (T-AOC) and malondialdehyde (MDA) content were used to evaluate the antioxidant activity of C3G liposomes. The C3G liposomes can obviously increased T-AOC and decreased the MDA content.Collectively, C3G liposomes protected human GES-1 cells from gastric mucosal injury induced by H2O2 by activating the related antioxidant pathway. Our research could provide a new effective treatment strategy for the absorption of stomach drugs.Abbreviations: C3G: Cyanidin-3-O-glucoside; LP: Liposome; GES-1 cells: Human gastric epithelial cell lines; FBS: Fetal Bovine Serum; PBS: Phosphate-buffered saline; PC: Phosphatidylcholine; CH: Cholesterol; MDA: Malondialdehyde; TEM: Transmission electron microscope; FCM: Flow cytometry; FITC: Fluorescein isothiocyanate; DAPI: 4', 6-diamidino-2phenylidole; FT-IR: Fourier Transform infrared spectroscopy; PFA: Paraformaldehyde.

Fabrication of Transgelosomes for Enhancing the Ocular Delivery of Acetazolamide: Statistical Optimization, In Vitro Characterization, and In Vivo Study.

Acetazolamide (ACZ) is a potent carbonic anhydrase inhibitor that is used for the treatment of glaucoma. Its oral administration causes various undesirable side effects. This study aimed to formulate transgelosomes (TGS) for enhancing the ocular delivery of ACZ. ACZ-loaded transfersomes were formulated by the ethanol injection method, using phosphatidylcholine (PC) and different edge activators, including Tween 80, Span 60, and Cremophor RH 40. The effects of the ratio of lipid to surfactant and type of surfactant on % drug released after 8 h (Q8h) and entrapment efficiency (EE%) were investigated by using Design-Expert software. The optimized formula was formulated as TGS, using poloxamers as gelling agents. In vitro and in vivo characterization of ACZ-loaded TGS was performed. According to optimization study, F8 had the highest desirability value and was chosen as the optimized formula for preparing TGS. F8 appeared as spherical elastic nanovesicles with Q8h of 93.01 ± 3.76% and EE% of 84.44 ± 2.82. Compared to a free drug, TGS exhibited more prolonged drug release of 71.28 ± 0.46% after 8 h, higher ex vivo permeation of 66.82 ± 1.11% after 8 h and a significant lowering of intraocular pressure (IOP) for 24 h. Therefore, TGS provided a promising technique for improving the corneal delivery of ACZ.

Niosomes for nose-to-brain delivery of bromocriptine: Formulation development, efficacy evaluation and toxicity profiling

The present study aimed to formulate stable non-ionic surfactant vesicles incorporating Bromocriptine Mesylate (BCM) to enhance brain uptake via the direct nose to brain pathway. The optimized formulation prepared by ethanol injection method exhibited a size of 180 ± 4.5 nm, % encapsulation of 75.8 ± 3.6 and zeta potential of −14.2 ± 1.8 mV. Ex vivo study demonstrated 6.4 times enhancement in permeation across goat nasal mucosa at 24 h as compared to BCM drug suspension. The relative brain bioavailability, drug targeting efficiency and direct transport percentage of intranasal (i.n) niosomes was found to be 1045.51%, 1118.10% and 91.06% respectively, suggesting enhanced CNS targeting via the direct olfactory pathway. Group treated with BCM niosomes i.n revealed a marked attenuation of cataleptic time along with reduced lipid oxidation and restored Glutathione (GSH) levels in the brain. Sub-acute toxicity studies carried out for 28 days revealed no mortality or toxicologically significant changes. The combination of above results proved that BCM niosomes were safe to be administered i.n displaying manifold enhancement in brain distribution and improved pharmacodynamic behavior with 10 times dose reduction. Thus, such a system could be positively exploited as an alternative to oral delivery in the management of Parkinson's Disease (PD).

Formulation and characterization of curcumin loaded polymeric micelles produced via continuous processing.

A continuous processing platform was developed to produce polymeric micelles. A block copolymer of mPEG (5kD)-PCL (2kD) was used as the model drug carrier. The polymeric micelles were produced using an innovative co-axial turbulent jet with co-flow continuous technology to precisely control the physicochemical properties of the micelles. A 3×3×4 full factorial design of experiment (DoE) study was conducted to optimize the polymeric micelle processing to achieve the desired critical quality attributes such as particle size and polydispersity index (PDI). Curcumin was used as a hydrophobic model drug as polymeric micelles are traditionally used to improve solubility and chemical stability of hydrophobic drug molecules. A second DoE study was conducted to achieve maximal drug loading. The average size of the optimized curcumin-loaded polymeric micelles was 29.1±0.51 d.nm with a PDI value in the range of 0.05±0.02 and a maximum drug loading of 11.1±0.81% (w/w). When compared to polymeric micelles prepared using a manual ethanol injection method the particle size, PDI and drug loading for curcumin-loaded polymeric micelles was 74.8±8.68 d.nm, and 0.46±0.12 and 8.12±1.23%, respectively. These data show that the continuous processing method provided significant improvement in controlling the key quality attributes. The curcumin-loaded polymeric micelles exhibited a sustained release profile during dissolution of about 50% drug released in 12h compared to the free drug, which was completely released within 10h. The curcumin-loaded polymeric micelles were characterized for other key quality attributes such as critical micelle concentration (CMC), and morphology by transmission electron microscopy, X-ray powder crystallography, polarized light microscopy, and differential scanning calorimetry. A novel method for determining the CMC of the polymer was developed using dynamic light scattering (DLS). Curcumin-loaded polymeric micelles were further processed by lyophilization to prevent hydrolytic cleavage of the polymers and maintain long term stability. The current study highlighted the potential advantages of transitioning from manual batch processing to continuous processing and serves as an example of improving processing efficiency as well as product quality through utilization of advanced processing technologies.

Identification of Abies sibirica L. Polyprenols and Characterisation of Polyprenol-Containing Liposomes.

The needles of conifer trees are one of the richest sources of natural polyprenols. Polyprenol homologs from Abies sibirica L. lipophilic 80% purified extract were analyzed and quantified. In total, 10 peaks (Prenol-11 to Prenol-20) were observed in the ultra-high-performance liquid chromatography–diode array detector (UHPLC-DAD) chromatogram of Siberian fir with the most abundant compound being Prenol-15 (relative amount 37.23 + 0.56% of the total polyprenol yield). Abies sibirica L. polyprenol solubility and incorporation efficiency into liposomes were studied in various commercially available lecithin mixtures (Phosal IP40, Phosal 75SA, and Lipoid P45). The resulting multilamellar polyprenol liposomes were morphologically characterized by Light and Transmission Electron Microscopy, and the liposome size was discovered to be polymodal with the main peak at 1360 nm (90% of the volume). As polyprenols are fully soluble only in lipids, a liposomal formulation based upon co-solubilization and a modified ethanol injection method of polyprenols into the ethanol-phospholipid system was developed for the entrapment and delivery of polyprenols for potential commercial applications in food supplement and cosmetic industries.

Preparation and In Vitro/Vivo Evaluation of Nano-Liposomal Form of Febrifugine Hydrochloride.

Febrifugine hydrochloride (FFH) has strong pharmacological antimalarial effect. However, compared with oral administration, the efficacy of intravenous administration is significantly reduced. In this study, we prepared conventional liposomes and PEGylated liposomes to improve the efficacy of its intravenous injection. Both liposome formulations were prepared using a modified ethanol injection method. Their mean particle sizes were 126.23 and 114.93 nm, mean zeta potentials were -6.25 and -26.33 mV, and entrapment efficiencies (EE) were 89.43 and 96.42%, respectively. The in vitro release profile indicated that the release of FFH from PEGylated liposomes and conventional liposomes was slower than free FFH, with sustained-release effect of PEGylated liposomes being more significant. PEGylated liposomes demonstrated excellent antimalarial activities in vitro superior to free FFH and conventional FFH-loaded liposomes. In addition, the PEGylated liposomes resulted in enhanced antimalarial effect in P. berghei infected mice in vivo with delayed recrudescence and prolonged survival time, compared with free FFH and conventional FFH-loaded liposomes administration. Based on these exciting experimental results, PEGylated liposomes could be a potential drug delivery system for FFH, with enhanced pharmacodynamics of intravenous injection.

Investigation on the Preparation, Characteristics, and Controlled Release Model of Paeonol-Loaded Liposome in Carbomer Hydrogel.

Paeonol is a phenolic compounce that is volatile. In order to decrease its volatility and achieve controlled release, paeonol-loaded liposome in carbomer hydrogel was prepared by coating with soybean phospholipid via ethanol injection method and then added into the carbomer hydrogel. The quality of paeonol-loaded liposome in carbomer hydrogel was evaluated by the degree of roundness, particle size distribution, zeta potential, entrapment efficiency (filtration method and chitosan neutralization method), viscosity, infrared spectrum, etc. Furthermore, the diffusion from paeonolloaded liposome in hydrogel was studied in vitro. The results showed that the average particle size of paeonol-loaded liposome was about 401 nm, the potential was -17.8 mV, and the entrapment efficiency was above 45%. The viscosity of paeonol- loaded liposome in hydrogel was 23.972×10-3 Pa*s, and the diffusion rate from paeonol-loaded liposome in hydrogel in vitro was obviously slower than that from the other paeonol preparations. The conclusions could be drawn that paeonol-loaded liposome in hydrogel was a kind of novel preparation, and its diffusion in vitro had obvious controlled-release characteristics, which further proved that it might improve the bioavailability of paeonol.

Phenylethyl Resorcinol Loaded in Liposomal Cream Formulation for Cosmeceutical Application

Phenylethyl Resorcinol (PR) is a cosmeceutical skin lightening agent and the purpose of this study was to enhance its stability by using liposomal cream formulation which increases local efficacy and safety. Liposome formulation was prepared by modified ethanol injection method, and it contained soy phosphatidyl choline (SPC), cholesterol (CHO), Tween 80 (TW80) and deoxycholic acid (DA) mixed with 2% PR. The physicochemical properties, skin permeation as well as cellular study were evaluated in order to obtain the optimized formulation. The optimized liposome formulation composed of SPC:TW80:DA (84:16:2.5) and exhibited vesicle size, polydispersity index (PDI) and zeta potential of 286.4±8.04 nm, 0.317±0.03 and -39.20±3.85 mV, respectively. Entrapment efficiency (EE) of liposome formulation was 93.55±0.05%. The vesicle was spherical in shape and showed good physicochemical stability for 4 months. The skin permeation study demonstrated that liposome with a negative charge could result in a high PR skin deposition value of 1732.76±216.24 µg/cm2 after 24 h. Cellular study showed that liposome formulation could inhibit melanin content in B16 melanoma cells and enhance cell viability in HaCaT keratinocyte cells. The optimized PR liposome was incorporated in cream and investigated physicochemical properties, stability and skin permeation. Liposomal PR cream showed a good stability and a superior result than PR cream in skin permeation parameters, as well as in tyrosinase inhibition.

Drug-in-hydroxypropyl-β-cyclodextrin-in-lipoid S100/cholesterol liposomes: Effect of the characteristics of essential oil components on their encapsulation and release.

Drug-in-cyclodextrin-in-liposome (DCL) represents a very promising approach for preserving essential oil (EO) components, thereby extending their shelf life and activity. In this study, we examined the effect of chemical structure, octanol/water partition coefficient (log P), and Henry's law constant (Hc) on the encapsulation and the release of monoterpenes (eucalyptol, pulegone, terpineol, and thymol) and phenylpropenes (estragole and isoeugenol) from DCLs. Hydroxypropyl-β-cyclodextrin/EO component (HP-β-CD/EO component) inclusion complexes were prepared in aqueous solution and loaded into liposomes by the ethanol injection method. The phospholipid:cholesterol:EO component molar ratio determined for DCL structures was affected by characteristics of EO components. The presence of a propenyl tail or a hydroxyl group in the structure of EO component may improve its loading into DCLs. Furthermore, low encapsulation efficiency (EE) was obtained for DCLs exhibiting high cholesterol membrane content. In addition, a positive linear relationship was found between the loading ratio of monoterpenes into DCLs and their hydrophobic character expressed as log P. The release of components from DCLs was influenced by their EE into the formulations. Finally, DCL formulations retain considerable amounts of EO components after 10months.

Silymarin Spray-Dried Proliposomes: Preparation, Characterization and Cytotoxic Evaluation

Background: Most liposomes problems are due to stability and consistency. Proliposomes is one of the solutions to overcome the disadvantage of liposomes. They are available in dry powder form, it is easy to distribute, transfer, measure and store. Objective: The aim of the present study was to find a novel method of preparing Silymarin proliposomes and study the effect of cholesterol concentrations and surfactant types on the physicochemical properties of silymarin proliposomes and its in-vitro release. Methods: Silymarin proliposomes were prepared by combining two simple methods ethanol injection method for liposomes preparation followed by the spray drying method to get a dry powder. The physicochemical properties including particle size, TEM, SEM, FTIR, encapsulation efficiency and dissolution studies were studied. Results: The particle size of silymarin liposomes were below 552.36 ± 17.63 nm but after reconstitution of silymarin proliposomes, the particle size was in the micro range due to the influence of the spray drying process. Cholesterol concentration was ranged from 50 to 150 mg per formula. Increasing Cholesterol concentration caused a significant increase in liposomes particle size and reduction in encapsulation efficiency. Three non-ionic surfactants were used to prepare silymarin proliposomes Tween 80, Cremophor RH 40 and Poloxamer 407. Formula F1 prepared with Phosal® 53 MCT (300 mg), Tween 80 (50 mg), cholesterol (50 mg) and Silymarin (140 mg) showed the smallest particle size (2066 ± 164.87 nm) upon reconstitution in water, highest encapsulation efficiency (89.51 ± 0.43%), and fastest in vitro release compared to other formulas. Cytotoxicity of Silymarin, formula F1 and formula F1/blank was assessed using an MTT assay on MCF-7, HepG2 and HBF-4 cells. The cytotoxic effect of silymarin was enhanced by loading it on proliposomes. Conclusion: Silymarin was successfully formulated into proliposomes combining ethanol injection and spray drying methods. The cytotoxicity of silymarin was improved when loaded on proliposomes owing to the formula.

Transfersomes — A Nanoscience in Transdermal Drug Delivery and Its Clinical Advancements

The convenient nanotransdermal delivery system is always likely to have some ideal and unique characteristics, predominantly for safety, desired actions, clinical efficacy, enriched with a therapeutic index with minimal adverse occurrence. One of the most challenging tasks for the formulators is to transfer the medicament, especially macromolecules, through the skin. Some of the ways to achieve this is the use of a painful needle or some other methods which also have economical constraints. A new technology has been developed, that is ultradeformable liposomes, also called as transfersomes. These are an elastic type of lipid vesicle aggregates capable of delivering wide range of active moieties including various biomolecules. It can be manufactured by evaporation, vortexing, reverse-phase evaporation, ethanol injection or freeze-thaw methods, where phospholipids and edge activators are the major ingredients that contribute the main role in their unique mechanism of permeation through less permeable stratum corneum. This review mainly focuses on the clinical trial studies and patents accessible on transfersomal products worldwide, highlights the recent work on transfersomes with various therapeutic agents. An effort to explain the deeper penetration of transfersomes across the epidermis layer by its pharmacokinetics and dynamic properties has been taken.

Ultra-deformable Liposomes as Flexible Nanovesicular Carrier to Penetrate Versatile Drugs Transdermally

Introduction: Transferosomes also known as ultra-deformable liposomes were introduced by Gregor Cevc in 1990. These are deformable vesicles that transport drug across the skin, which is the best route of drug delivery because skin is the largest human organ with 3 kg total weight and a surface area of 1.5-2.0 m2. Methods: Transferosomes are able to efficiently deliver low as well as high molecular weight drug across the skin in terms of quantity and depth. Various methods used for the preparation of transferosomes such as thin film hydration method, reverse phase evaporation method, vortex/sonication method, ethanol injection method and freeze thaw method. Results: The prepared transferosomal preparation will be evaluated for particle shape and size, entrapment efficiency, stability study, penetration ability and skin permeation study. In vitro release studies are to be performed using a specific dissolution medium. Conclusion: Ultra deformable liposomes can be used for delivery of different drugs e.g. analgesic, anesthetic, corticosteroids, anticancer, sex hormone, insulin, gap junction protein, and albumin.

The transdermal performance, pharmacokinetics, and anti-inflammatory pharmacodynamics evaluation of harmine-loaded ethosomes

Harmine (HAR) is a β-carboline alkaloid with anti-inflammatory and antipruritic effect. However, the low bioavailability and side effects of HAR severely limited its clinical application. The main objective of this study was to develop harmine-loaded ethosomes (HLE) drug delivery system for topical application to treat inflammation. HLE were obtained by ethanol injection method and characterized. The morphology of HLE was evaluated by transmission electron microscopy (TEM). HLE exhibited a good biocompatibility with human embryonic skin fibroblasts and rat skin. The in vitro skin penetration studies showed that HLE had the greatest skin deposition than harmine-loaded liposomes (HLL) and harmine solution (HS). In vivo pharmacokinetic study demonstrated that AUC(0–∞) and Cmax of HLE in subcutaneous tissues were much higher than that of in blood. Moreover, for convenience of fixing on skin, HLE were mixed with gel. HLE gel significantly inhibited the overexpression of inflammation cytokines prostaglandin E2, interleuking (IL)-1β, nitric oxide, and tumor necrosis factor-alpha (TNF-α) in the inflammation model of rat paw edema compared with HS gel. In short, HLE was promising formulation for topical delivery in treatment of inflammatory diseases.

Formulation and evaluation of Metformin Hydrochloride-loaded Curcumin–Lycopene Niosomes

Curcumin and lycopene, both are naturally occurring potent antioxidants which can be used in the treatment of oxidative stress. The biological sources to obtain curcumin and lycopene are curcuma longa and Solanum lycopersicum, respectively. The aim of this research study is to develop curcumin–lycopene conjugate-based biguanide niosomes. Span 60 as non-ionic surfactant and cholesterol as a stabilizer were used for the preparation of metformin hydrochloride-loaded niosomes by the ethanol injection method. This research dealt with the composition, formulation, evaluation and optimization of niosomes. The particle size and polydispersity index were found to be in the range from 139.6 to 509 and 0.152 to 0.541 nm, respectively. The entrapment efficiency and drug loading capacity were observed in the range of 40.43–79.02 and 26.954 to 78.17%, respectively. The in vitro drug release studies showed the sustained release of drug in all formulations up to the period of 24 h. Kinetic analysis of in vitro drug release studies showed that when the ratio of Span 60 and cholesterol is 1:1.5 and 1:2, the formulations followed first-order kinetics. When the ratio changed to 1:1, the formulation followed the Korsmeyer–Peppas model and finally at the ratio of 1.5:1 and 2:1, formulations followed the Higuchi kinetics and Hixson–Crowell kinetics, respectively. Formulation S2 is concluded as an optimized formulation on the basis of all evaluation parameters.

Modified Spraying Technique and Response Surface Methodology for the Preparation and Optimization of Propolis Liposomes of Enhanced Anti-Proliferative Activity against Human Melanoma Cell Line A375.

Propolis is a honeybee product that contains a mixture of natural substances with a broad spectrum of biological activities. However, the clinical application of propolis is limited due to the presence of a myriad of constituents with different physicochemical properties, low bioavailability and lack of appropriate formulations. In this study, a modified injection technique (spraying technique) has been developed for the encapsulation of the Egyptian propolis within liposomal formulation. The effects of three variables (lipid molar concentration, drug loading and cholesterol percentage) on the particle size and poly dispersity index (PDI) were studied using response surface methodology and the Box–Behnken design. Response surface diagrams were used to develop an optimized liposomal formulation of the Egyptian propolis. A comparative study between the optimized liposomal formulation prepared either by the typical ethanol injection method (TEIM) or the spraying method in terms of particle size, PDI and the in-vitro anti-proliferative effect against human melanoma cell line A375 was carried out. The spraying method resulted in the formation of smaller propolis-loaded liposomes compared to TEIM (particle sizes of 90 ± 6.2 nm, and 170 ± 14.7 nm, respectively). Furthermore, the IC50 values against A375 cells were found to be 3.04 ± 0.14, 4.5 ± 0.09, and 18.06 ± 0.75 for spray-prepared propolis liposomes (PP-Lip), TEIM PP-Lip, and propolis extract (PE), respectively. The encapsulation of PE into liposomes is expected to improve its cellular uptake by endocytosis. Moreover, smaller and more uniform liposomes obtained by spraying can be expected to achieve higher cellular uptake, as the ratio of liposomes or liposomal aggregates that fall above the capacity of cell membrane to “wrap” them will be minimized.

Formulation and Characterization of Taxifolin‐Loaded Lipid Nanovesicles (Liposomes, Niosomes, and Transfersomes) for Beverage Fortification

AbstractIn this study, nanovesicles such as transfersomes, niosomes, and liposomes prepared by an ethanol injection method (EIM) (EIM) and formulated with soybean lecithin, Tween 80, Span 60, and cholesterol, are used to improve the bioavailability of taxifolin, a natural antioxidant with beneficial properties for health and food preservation. Morphology, stability, and the in‐vitro release of the optimal formulations are fully examined. The obtained results indicate that taxifolin‐loaded nanovesicles present sizes ranging between 98 and 215 nm along with a narrow size distribution (polydispersity index less than 0.250). The zeta potential of nanovesicles is negative and in the range of −20.40 to −32.20 mV. The optimal formulations with the maximum encapsulation efficiency (72–75%) are the transfersomes formulated with lecithin and Tween 80 in the presence and absence of cholesterol. Additionally, in vitro release behavior of nanovesicles shows low taxifolin released (3.68–10.13%) at intestinal conditions, whereas more than 90% of taxifolin is released in gastrointestinal conditions. The compatibility between taxifolin and nanovesicles components is confirmed by FTIR. Transmission electron microscopy demonstrates spherical shaped particles around 200 nm. Backscattering profiles variations show the potential application of taxifolin nanovesicles for producing fortified apple juice with excellent physical stability.Practical Applications: Taxifolin is a flavanonol, which fulfills a particular task in preserving stable functions of the circulatory system owing to its special antioxidant ability and biological activity. Nevertheless, its low bioavailability is a salient drawback for biomedical and food applications. Thus, the current study is conducted to encapsulate taxifolin in nanovesicles (such as liposome, niosome, transfersome) by EIM to improve its bioavailability. Nanocarriers with relatively decent physical stability and high encapsulation efficiency can be brought about through Tween 80, soybean lecithin, and in the presence and absence of cholesterol as stabilizer which ensures the successful delivery of taxifolin to food formats such as beverages.

A novel transdermal nanoethosomal gel of lercanidipine HCl for treatment of hypertension: optimization using Box-Benkhen design, in vitro and in vivo characterization.

Poor bioavailability of drugs via oral route is the greatest challenge facing drug formulation. To overcome this obstacle, transdermal route was commonly used as an alternative route to improve bioavailability. Lercanidipine HCl (LER) is a vasoselective calcium-channel blocker that has a poor oral bioavailability of 10% due to its hepatic metabolism and low solubility. The main objective of this study was to develop nanoethosomal LER gel for transdermal delivery to increase its skin permeation and promote bioavailability. Nanoethosomes were prepared and optimized using a Box-Behnken design employing ethanol injection method. The design studied the influence of Phospholipon 90G (PL90G), LER, and ethanol concentrations on entrapment efficiency (EE%); vesicle size; % cumulative LER release (CLERR); and cumulative LER permeated per unit area at 24h Q24 (μg/cm2). The pharmacokinetic parameters of the optimized formulation were determined in rats. Nanoethosomes showed a mean vesicle size between 210.87 and 400.57nm and EE% ranging from 49.26 to 97.22%. The developed nanoethosomes enhanced % CLERR and Q24 values compared to drug suspension. The experimental parameters of optimized formulation were very close to those calculated by software. The pharmacokinetics study showed three times statistically significant (p < 0.05) enhancement in LER bioavailability following nanoethosomal LER gel transdermal application compared to that of oral LER suspension. Nanoethosomes can be considered as a promising carrier for LER transdermal delivery, thus will be fruitful therapy in hypertension management. Graphical abstract.