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One of the most effective strategies to fight viruses and handle health diseases is vaccination. Recent studies and current applications are moving on antigen, DNA and RNA-based vaccines to overcome the limitations related to the conventional vaccination strategies, such as low safety, necessity of multiple injection, and side effects. However, due to the instability of pristine antigen, RNA and DNA molecules, the use of nanocarriers is required. Among the different nanocarriers proposed for vaccinal applications, three types of nanovesicles were selected and analysed in this review: liposomes, transfersomes and niosomes. PubMed, Scopus and Google Scholar databases were used for searching recent papers on the most frequently used conventional and innovative methods of production of these nanovesicles. Weaknesses and limitations of conventional methods (i.e., multiple post-processing, solvent residue, batch-mode processes) can be overcome using innovative methods, in particular, the ones assisted by supercritical carbon dioxide. SuperSomes process emerged as a promising production technique of solvent-free nanovesicles, since it can be easily scaled-up, works in continuous-mode, and does not require further post-processing steps to obtain the desired products. As a result of the literature analysis, supercritical carbon dioxide assisted methods attracted a lot of interest for nanovesicles production in the vaccinal field. However, despite their numerous advantages, supercritical processes require further studies for the production of liposomes, transfersomes and niosomes with the aim of reaching well-defined technologies suitable for industrial applications and mass production of vaccines., (© 2024. The Author(s).)

Background and objectives: Liposomal structures are artificial vesicles composed of one or several lamellae of phospholipids which surround an inner aqueous core. Given the amphoteric nature of phospholipids, liposomes are promising systems for drug delivery. The present review provides an updated synthesis of the main techniques for the production of liposomes for orthopedic applications, focusing on the drawbacks of the conventional methods and on the advantages of high pressure techniques. Materials and Methods: Articles published in any language were systematically retrieved from two major electronic scholarly databases (PubMed/MEDLINE and Scopus) up to March 2020. Nine articles were retained based on the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines. Results: Liposome vesicles decrease the rate of inflammatory reactions after local injections, and significantly enhance the clinical effectiveness of anti-inflammatory agents providing controlled drug release, reducing toxic side effects. Conclusions: This review presents an update on the improvement in musculoskeletal ailments using liposome treatment.

Supercritical fluid extraction using a high-pressure packed tower is proposed not only to remove the ethanol residue from liposome suspensions but also to affect their size and distribution leading the production of nanosomes. Different operating pressures, temperatures, and gas to liquid ratios were explored and ethanol was successfully extracted up to a value of 400 ppm; liposome size and distribution were also reduced by the supercritical processing preserving their integrity, as confirmed by Z-potential data and Trasmission Electron Microscopy observations. Operating at 120 bar and 38°C, nanosomes with a mean diameter of about 180 ± 40 nm and good storage stability were obtained. The supercritical processing did not interfere on drug encapsulation, and no loss of entrapped drug was observed when the water-soluble fluorescein was loaded as a model compound. Fluorescein encapsulation efficiency was 30% if pure water was used during the supercritical extraction as processing fluid; whereas an encapsulation efficiency of 90% was obtained if the liposome suspension was processed in water/fluorescein solution. The described technology is easy to scale up to an industrial production and merge in one step the solvent extraction, liposome size engineering, and an excellent drug encapsulation in a single operation unit., (© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.)

Vesicles are intriguing candidates for the topical administration of cosmetics as they can act as skin penetration stimulators, the individual components of the vesicles can impart additional desired properties to cosmetics, and are biodegradable and minimally toxic. Among the vesicular systems proposed for this application, liposomes are widely investigated. They are constituted of an inner aqueous core and an outer lipid bilayer. This configuration allows the encapsulation of both lipophilic and hydrophilic bioactive drugs. However, the traditional processes proposed for the production of these vesicles suffer from several limits: they are batch and time-consuming techniques, require post-treatments for the purification of vesicles from organic solvent residues and/or for reducing their mean size, do not favour a high encapsulation efficiency of drugs. In this work, SuperSomes, a sustainable and continuous process assisted by supercritical CO2, was used to produce nanometric liposomes loaded with ascorbic acid for cosmetic applications. Operating at 100 bar and 40 °C, stable liposomes characterized by a spherical morphology and a mean diameter lower than 250 nm, were obtained. An ascorbic acid encapsulation efficiency of 85% was measured and the supercritical process preserved the antioxidant activity of the drug. [ABSTRACT FROM AUTHOR]

Liposomes have been used for several decades for the encapsulation of drugs and bioactives in cosmetics and cosmeceuticals. On the other hand, the use of these phospholipid vesicles in food applications is more recent and is increasing significantly in the last ten years. Although in different stages of technological maturity—in the case of cosmetics, many products are on the market—processes to obtain liposomes suitable for the encapsulation and delivery of bioactives are highly expensive, especially those aiming at scaling up. Among the bioactives proposed for cosmetics and food applications, vitamins are the most frequently used. Despite the differences between the administration routes (oral for food and mainly dermal for cosmetics), some challenges are very similar (e.g., stability, bioactive load, average size, increase in drug bioaccessibility and bioavailability). In the present work, a systematic review of the technological advancements in the nanoencapsulation of vitamins using liposomes and related processes was performed; challenges and future perspectives were also discussed in order to underline the advantages of these drug-loaded biocompatible nanocarriers for cosmetics and food applications. [ABSTRACT FROM AUTHOR]

Encapsulation of antibodies represents a significant advance to protect and deliver these therapeutics in a controlled manner, increasing the stability requested to cover the temporal gap between particle production and their administration. Furthermore, using encapsulation, extracellular, cell surface, and intracellular targets can be reached. This work examines the feasibility of encapsulating mouse IgG isotype control antibodies within phosphatidylcholine-based liposomes using a supercritical fluid-based process called SuperLip (Supercritical-assisted Liposome formation). This process allows a continuous production of both nano- and micrometric liposomes with high encapsulation efficiency working under mild operative conditions. The effect of some operative parameters has been studied on liposome mean diameter, particle size distribution, and antibody entrapment efficiency, comparing these data with those collected working with liposomes obtained by the thin-layer hydration technique. In particular, the effect of water flow rate and of the antibody loading were studied. Antibody-loaded liposomes with mean diameters in the range between 205 and 501 nm have been obtained by using a supercritical fluid-assisted process. High entrapment efficiencies up to 94% have been calculated. [ABSTRACT FROM AUTHOR]

In this work, a lipophilic ophthalmic drug, lutein, has been entrapped in liposomes, using a supercritical assisted process. Effects of pressure, temperature, and drug to lipid ratio variation were studied on mean diameters and lutein encapsulation efficiency. Liposomes with diameters between 153 ± 38 and 267 ± 56 nm were produced, and lutein encapsulation efficiencies between 86.5 ± 0.4% and 97.8 ± 1.2% were obtained. A Scanning Electron Microscope confirmed spherical shape and mean dimensions of vesicles. The variation of temperature for the production of liposomes showed a significant impact on lutein retention time in the double lipidic layer. Lutein drug release from liposomes produced at 35 °C ended in almost 4.5 days; whereas, liposomes produced at 40 °C showed a faster lutein release in 3 days; then, vesicles obtained at 45 °C released their lutein content in only 2 days. Drug release raw data were well-fitted using Weibull model (R2 up to 99%). [ABSTRACT FROM AUTHOR]

• Supercritical assisted method for the production of PEGylated liposomes. • PEG-coverage of liposomes confirmed by SEM observations. • Entrapment efficiency up to 92 % of artesunate in PEGylated liposomes. • Controlled drug release of artesunate from PEGylated liposomes. Liposomes are spherical vesicles, characterized by spontaneous aggregation tendency. To overcome this problem, in this work, liposomes coating was attempted, using polyethylene glycol (PEG), at different polymer to lipid ratios (1, 5, 10 % w/w) and proposing two experimental protocols, based on a supercritical assisted process. Only one protocol was successful; in that case, size and SEM analysis confirmed that vesicles did not aggregate thanks to the repulsion created by PEG surface, as confirmed by zeta potential measurements (about -25 mV). Liposomes with mean size ranging between 134 ± 30 and 166 ± 45 nm, stable for at least 70 day, were produced. The efficiency of SuperLip to produce PEG-coated liposomes was also tested, entrapping artesunate, obtaining encapsulation efficiencies up to 92 %. Drug release tests for standard and PEG-coated liposomes were compared: PEGylated vesicles produced a controlled release at least three times longer, without a significant initial burst release. [ABSTRACT FROM AUTHOR]

Supercritical assisted Liposome formation (SuperLip) is a lab-scale process for the production of liposomes. SuperLip was recognized as being a versatile supercritical assisted technique for the encapsulation of molecules for different industrial applications, such as pharmaceutic, cosmetic, textile, and nutraceutic purposes. The aim of this work was to perform an economic analysis to assess the profitability of the SuperLip process. The liposomes market was analyzed and the SuperLip process was compared to other techniques in terms of manufacturing advantages using the Canvas and Strengths, Weaknesses, Opportunities, and Treats (S.W.O.T.) models. SuperLip Plant Capital Expenditures (CAPEX) were estimated, and plant Operating Expenditures (OPEX) were also evaluated and integrated with personnel cost and other plant goods and services. A profit and loss statement was generated, together with a cash flow analysis. According to the market average selling price, liposome price is 1.8 €/mL; in order to join the market rapidly, the selling price of liposomes produced using SuperLip was set at 1.1 €/mL. A payback time has been identified at the fourth year of business. Economic indexes such as ROI and ROS were calculated on a 10-year business prospect, obtaining about a 230% return on investment and a 26.7% return on sales. [ABSTRACT FROM AUTHOR]

Liposomes are spherical vesicles made up of an aqueous core surrounded by phospholipids. These delivery systems (DS) are largely employed as drug carriers in several industrial fields, such as pharmaceutical and nutraceutical fields. The aim of this short review is to provide a fast overview on the main fundamentals of liposomes, thought as a compact guide for researchers and students that want to approach this topic for the first time. The mini-review will focus on the definitions, production methods and characterization protocols of the liposomes produced, making a critical comparison of the main conventional and supercritical based manufacturing methods available. The literature was analyzed deeply from the first works by Dr. Bangham in 1965 to the most recent supercritical fluid applications. The advantages and disadvantages of conventional and high-pressure processes will be described in terms of solvent elimination, production at the nanometric (50–300 nm) and micrometric level (1–100 μm) and encapsulation efficiency (20–90%). The first proposed methods were characterized by a low encapsulation efficiency (20–40%), resulting in drug loss, a high solvent residue and high operating cost. The repeatability of conventional processes was also low, due to the prevalent batch mode. Supercritical-assisted methods were developed in semi-continuous layouts, resulting in an easy process scale-up, better control of liposome dimensions (polydispersity index, PDI) and also higher encapsulation efficiencies (up to 90%). [ABSTRACT FROM AUTHOR]

• Ampicillin loaded liposomes were entrapped in alginate aerogels to create a meta-carrier. • SuperLip favored the production of liposomes at nanometric level. • Alginate gel nanoporous structure was preserved by supercritical drying. • Ampicillin release time from meta-carriers was twice than its release from liposomes alone. Ampicillin loaded liposomes were entrapped in alginate aerogels to create a meta-carrier (a carrier within another carrier), to obtain a prolonged drug release. Liposomes with a diameter of 200 ± 77 nm and with an encapsulation efficiency of 69.5 ± 1.2% were produced using a supercritical assisted formation process (SuperLip). Then, they were entrapped into alginate gels, and the final loaded aerogels were obtained by supercritical CO 2 drying. The successful entrapment of liposomes into aerogels was confirmed by EDX analysis. Drug release tests demonstrated that ampicillin release time from these meta-carriers was about 4 days; i.e., about twice than its release time from liposomes alone. Two mass transfer resistances in series operated in the overall drug release: one related to liposomes lipidic layers and one due to the presence of the alginate aerogel matrix. [ABSTRACT FROM AUTHOR]

A supercritical CO 2 assisted process was used to perform a comparative study between liposomes and niosomes. Process operating conditions were fixed at 100 bar and 40 °C, and the produced vesicles were characterized in terms of mean diameter, size distribution, ζ-potential, and stability over time. Mean diameters of liposomes and niosomes were similar (130 ± 37 nm for liposomes and 141 ± 36 nm for niosomes) and both systems were stable after 1 month from production. Ascorbic acid (AA) was loaded in both kinds of formulation. AA encapsulation efficiency was equal to 92 % and 99 % for liposomes and niosomes, respectively, and DPPH-activity was larger than 90 % in both vesicular systems. Drug release tests revealed that AA was released in 120 min and 240 min from liposomes and niosomes, respectively, due to a different compactness of the vesicle bilayer. [Display omitted] • Successful production of nanoliposomes and nanoniosomes using a supercritical CO 2 assisted process. • Mean diameters of liposomes and niosomes were similar. • Ascorbic Acid (AA) encapsulation efficiency of 92 % and 99 % for liposomes and niosomes, respectively. • Longer AA release time in the case of niosomes due to the compactness of the vesicle bilayer. [ABSTRACT FROM AUTHOR]

To preserve benefic effects of antioxidants, they can be protected using a drug carrier. Conventional processes for the production of antioxidants-loaded carriers suffer of some drawbacks that can be overcome using Supercritical Assisted Liposome Formation (SuperLip). In this work, SuperLip was used to encapsulate an amphiphilic (eugenol, EUG) and a lipophilic (α-lipoic acid, ALA) antioxidant in liposome vesicles. EUG loaded liposomes were produced with a mean diameter of about 200 nm and demonstrated to be stable for at least 40 days. Eugenol was entrapped in the inner core and in the lipophilic double layer, with Encapsulation Efficiencies (EE) up to 94.2 ± 2.9%. Liposomes with a mean diameter of about 230 nm loaded with ALA in the lipidic layer were also successfully produced, with EE up to 68.1 ± 6.1%. Free-radical scavenging assay results indicated that EUG and ALA antioxidant power was preserved after processing; a reduction of the inhibition power, compared to the un-processed molecule, in the range between 6% and 13% was obtained. Drug release tests were also performed at 30 °C and 60 °C, showing that these liposomes are temperature sensitive. [ABSTRACT FROM AUTHOR]

Recently a new supercritical assisted process was proposed in the literature for the production of liposomes, called Supercritical Assisted Liposome formation (SuperLip) process. It has been demonstrated that, using this new process, it is possible to produce liposomes based on phosphatidylcholine (PC) with a controlled particle size distribution. Also a preliminary encapsulation test revealed a high encapsulation efficiency of bovine serum albumin (BSA), used as model hydrophilic compound. Being convinced of the great potential of the SuperLip process, in this work it has been studied the possibility of producing liposomes with a different composition of the bilayer membrane using the SuperLip process. Phosphatidylcholine (PC) and phosphatidylglycerol (PG) were used in a mixture and the production of liposomes was tested under different operative conditions: pressure, temperature and lipid composition. Results obtained using only PC and PC/PG mixture have been systematically compared. Furthermore a deepened study about the possibility to encapsulate BSA as model compound was performed. SuperLip experiments using different amount of BSA dissolved in the water internal phase were performed and the relative encapsulation efficiencies of produced liposomes were estimated. A comparison of encapsulation efficiency of liposomes produced, at the same BSA loadings, using a conventional preparation process (Bangham method) was also performed. The stability of entrapped protein was investigated. Sub-micrometric liposomes of soybean phosphatidylcholine (PC) of different size and distribution ranging between 250 ± 58 nm and 330 ± 82 nm were successfully produced. When using PG coupled with PC, larger liposomes were produced, ranging between 280 ± 70 nm and 350 ± 101 nm. Both PC and PC/PG liposomes were stable over one month, thanks to the large and negative surface charge (zeta potential ranging between −20 mV and −30 mV). For the drug encapsulation tests different BSA theoretical loadings with respect to the lipid amount (10–30–60%, w/w) were tested. In the case of SuperLip process, very high encapsulation efficiencies (92–98%) were obtained at all the drug loadings; lower encapsulation efficiencies were instead obtained using the Bangham method (2–57%). Results reported in this work demonstrated that using SuperLip process, the protein contained in the water phase can be efficiently entrapped without damaging the protein structure as confirmed by FTIR analysis of processed BSA. [ABSTRACT FROM AUTHOR]

Highlights: [•] A new supercritical assisted process for liposomes production is proposed. [•] Liposome suspensions with diameters ranging between 120 and 300nm are obtained. [•] An interpretation of liposome formation mechanism is attempted. [ABSTRACT FROM AUTHOR]

In this study, SuperLip, an innovative technology assisted by supercritical carbon dioxide (SC–CO 2), was used to produce unloaded and vitamin D 3 (VD3)-loaded nanoliposomes. Vesicles were produced using hydrogenated and nonhydrogenated phosphatidylcholine from food-grade lecithins at ratios of 30:70, 20:80 and 0:100. SuperLip was operated at 100 bar and 40 °C using water flow rates ranging from 2.5 to 10 mL/min. The results showed that unloaded liposomes produced by SuperLip presented a unimodal size distribution at a water flow rate of 10 mL/min, regardless of the phospholipid ratio, and mean diameters ranging from 125 to 141 nm. VD3-loaded liposomes also presented a unimodal size distribution at this water flow rate, but slightly higher diameters that ranged from 144 to 252 nm. Furthermore, the addition of 20% purified phospholipids to liposomes led to an increase in the mean size of VD3-loaded vesicles from 144 to 218 nm and an increase in the encapsulation efficiency from 66.7 to 88.9%. [Display omitted] • Mixed phospholipid liposomes were produced using a supercritical assisted process. • Nanosized vesicles with unimodal size distribution were obtained. • Higher water flow rates contributed to the formation of more stable nanoliposomes. • The amount of saturated phospholipids influenced vesicle size and PDI. • Vitamin D 3 was efficiently entrapped into nanoliposomes up to 88.9%. [ABSTRACT FROM AUTHOR]

• A combined process for bioactive extraction and preservation was proposed. • High pressure and temperature extraction allowed spent coffee grounds valorization. • Extract was rich in polyphenols and caffeine exhibiting high scavenging activity. • Produced loaded liposomes showed small size and high encapsulation efficiency. Valorization of agro-industrial waste by the extraction of bioactive molecules and their activity preservation by encapsulation is an open topic in process engineering. In this work, a combined approach for the recovery of antioxidants from spent coffee grounds by High Pressure and Temperature Extraction and the entrapment of extract into liposomes using the Supercritical assisted Liposome formation process was proposed. High Pressure and Temperature Extraction showed that high extraction performances (43 ± 2.3 mg Caffeic Acid Equivalents /g Dried Spent Coffee Grounds , 59 ± 3 μg Trolox Equivalents /L extract) can be obtained working under inert atmosphere at 150 °C, 60 min using ethanol 54 % (v/v) as solvent. For extract preservation, liposomes were produced by Supercritical assisted liposome formation, investigating different operating pressures and varying the extract cargo into liposomes. Results indicated that 100 bar as operative pressure and 18 mg Caffeic Acid Equivalents /g liposomes as total polyphenol loading allowed to obtain high encapsulation efficiency (89 %), small liposome size (about 200 nm) and without significant reduction of loading antioxidant activity (7%). [ABSTRACT FROM AUTHOR]