Progress 05/01/17 to 04/30/21
Outputs
Target Audience:Scientists and engineering with interest in delivery of bioactive materials. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Two post-doctoral associate, one Ph.D. student and one chemical engineering undergraduate were trained in supercritical fluid-based liposome generation technology. How have the results been disseminated to communities of interest?Through publication in scientific journals and presentations at professional meetings. What do you plan to do during the next reporting period to accomplish the goals?The project has been completed.
Impacts
What was accomplished under these goals?
Chitosan (Cs) and beta-lactoglobulin (βlg)decoratedliposomes were synthesized using phophotidal choline (PC), by using our Vent-RESS system. To determine the efficacy of bioactive encapsulation in the synthesized liposomes, vitamin E was used as a model lipophilic bioactive; and vitamin C was used as model hydrophilic bioactives. Synthesized liposomes demonstrated a unimodal size distribution with an average diameter of 392 nm and ζ-potential of −55 mV. Cs-βlg dual-coating resulted in a 2.4-fold increase in diameter and ζ-potential changed to 16 mV due to positive charge of βlg below its isoelectric point (~5.2). The presence of double-layer was also observed by confocal laser scanning microscopy and freeze-fracture cryo-scanning electron microscopy. The EE of vitamins E and C in the liposomes were around 92 and 70 %, respectively. In SGF, the dual Cs-βlg coating was able to resist acid-hydrolysis and pepsin-degradation for 2 h; while in SIF, the βlg coating was degraded by pancreatin causing release of around 80% of encapsulated bioactives. Synthesized liposomes were coated with Cs first. A Cs solution (0.15 % w/v) was prepared, and the pH of the solution was maintained at 4.5 by the addition of 1 % acetic acid solution. Concentrated liposomal solution was then added dropwise to the polymer solution under continuous stirring to achieve an equivolumetric mixture (1:1 volume ratio) at pH 4.5. The suspension was equilibrated overnight at 4 oC. The excess chitosan was separated by ultrafiltration. Next, Ch-L was coated with a secondary wall of native-βlg to produce double wall coated liposomes (βlg-Ch-L). βlg demonstrates a positive charge below its isoelectric point (~5.2) and Ch-L will be coated with βlg (0.05 % w/v) through ionic gelation by the aid of sodium tripolyphosphate (TPP) at pH 4.5. Native-βlg solution (0.15 % w/v) was prepared by adding βlg in deionized water with thorough mixing at room temperature for 1 h. The solution was then equilibrated for 2 h before further treatment to allow a good protein hydration. Concentrated solution of Ch-L was dropwise added to equal volume of βlg solution followed by addition of a TPP solution (1 mg/mL) solution at pH 4.5 under continuous stirring. The suspension was then equilibrated overnight at 4 oC followed by removal of excess βlg by using ultrafiltration membrane. Concentrated βlg-Ch-L was separated in a 6 mM acetic acid-sodium acetate buffer (pH 4.5). The effectiveness of the pH-responsive Cs-βlg coating was evaluated for cargo release under simulated gastric (SGF) and intestinal fluids (SIF). Coated liposomes were also characterized for their EE and morphological features. Synthesized liposomes demonstrated a unimodal size distribution with an average diameter of 392 nm and ζ-potential of −55 mV. Cs-βlg dual-coating resulted in a 2.4-fold increase in diameter and ζ-potential changed to 16 mV due to the positive charge of βlg below its isoelectric point (~5.2). The presence of double-layer was also observed by confocal laser scanning microscopy and freeze-fracture cryo-scanning electron microscopy. The EE of vitamins E and C in the liposomes were around 92 and 70 %, respectively. In SGF, the dual Cs-βlg coating was able to resist acid-hydrolysis and pepsin-degradation for 2 h; while in SIF, the βlg coating was degraded by pancreatin causing release of around 80% of encapsulated bioactives. As an addition to our work related to heatstable liposomes synthesized from MFGM phospholipids; liposomes were synthesized from MFGM too. To facilitate their application as an effective oral delivery vehicle, MFGM-liposomes were coated with a commercially available pH-responsive polymer, Eudragit S100. Eudragit S100 is a Methyl methacrylate methacrylic acid copolymer (1:2 copolymer ratio) and it dissolves over pH 7.0 thus it will protect the core load until reaching the target site in the gastrointestinal tract followed by degradation of the outer membrane and site-specific release of the encapsulated bioactives. Furthermore, Eudragit S 100's high glass transition temperature (161- 167 o C) will provide extra protection during treatment at elevated temperature. To coat bioactive loaded liposomes with Eudragit S100 we used polyethylene glycol (PEG) as a non-toxic solvent. PEG is non-immunogenic, uncharged linear polymer and is generally recognized as safe (GRAS). Liposomes were coated with Eudragit by using a nanoprecipitation method. This method requires two solvents that are miscible and a polymer that dissolves in one solvent and insoluble in the other one (i.e., non-solvent). Nanoprecipitation occurs when the polymer solution is added to the non-solvent. PEG-400 and 6-mM acetic acid-sodium acetate buffer (pH 4.5) were used as solvent and non-solvent, respectively. Eudragit S100 is soluble in PEG 400 at low concentration and is insoluble in acidic buffer. 50 mg of Eudragit S100 was dissolved in 3 mL of PEG-400 followed by adding 2 mL of concentrated liposomal dispersion. After thorough mixing the resultant solution was added dropwise in the acetic acid-sodium acetate buffer (pH 4.5) (non-solvent) under magnetic stirring and was kept at 4 oC for 4 h. Prepared Eudragit coated liposomes (Eu-L) were then separated by centrifugation and, after being washed three times with the acetic acid-sodium acetate buffer (pH 4.5), were kept in the same buffer. Both coated and uncoated liposomes were subjected to heat treatment at three different temperatures (60, 75, and 90 °C) for 30 minutes by immersing them in a constant temperature water bath. Post heat-treatment, all samples were subjected for morphological characterization by CLSM. Their EE%, diameter, and ζ-potential values were also measured as well for comparative analysis. The effectiveness of the pH responsive Eudragit coating was evaluated for cargo release under SGF and SIF. Liposomes synthesized from MFGM demonstrated an average diameter and ζ-potential of 429.4 ± 34 nm and −45.1 ± 4.36 mV. When these liposomes were coated in Eudragit, the diameter increased significantly by a factor of 1.57 to give a diameter of 1104.8 ± 96 nm. Eudragit coated liposomes demonstrated a ζ-potential of −36.7 ± 2.09 mV. The CLSM micrographs of coated liposomes before and after 30 minutes of heat treatment established the presence of intact liposomes even after heat-treatment. No significant change in diameter and ζ-potential of Eudragit coated liposomes was observed after heating at 60, 75, and 90 °C for 30 minutes. Whereas in our previous study when uncoated MFGM liposomes were subjected to heat-treatment; no significant change (p > 0.05) in liposomal diameter was observed after heating at 60 °C for 30 minutes. However, when heated at 75 and 90 °C, the diameter of MFGM liposomes significantly increased by factors of 1.6 and 2.0 respectively. Thus, coating of liposomes with Eudragit helped to sustain liposomal structural integrity. For coated liposomes the EE of vitamin E, held constant after heating to 60 - 90 °C. For vitamin C, the EE held constant at 60 - 75 °C, but decreased significantly after heat treatment at 90 °C.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Jash, A., Ubeyitogullari, A., & Rizvi, S. S. (2021). Liposomes for oral delivery of protein and peptide-based therapeutics: challenges, formulation strategies, and advances. Journal of Materials Chemistry B.
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Progress 05/01/19 to 04/30/20
Outputs
Target Audience:The research and development community in food and pharmaceutical industries. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?The project has supported one graduate student, one post-doctoral fellow and one undergraduate student. How have the results been disseminated to communities of interest?Through four peer-reviewed publications in journals of high impact factors. What do you plan to do during the next reporting period to accomplish the goals?1) Investigate the coating mechanics of cargo loaded liposomes decorated with pH responsive double-wall of chitosan (CS) and beta-Lactoglobulin (beta-Lg). 2) Fortify non-fat yogurt with coated liposomes, loaded with vitamin D3 and iron, and study stability under storage at selected temperatures and evaluate pH-triggered release kinetics of bioactives cargo under simulated gastrointestinal conditions.
Impacts
What was accomplished under these goals?
Phosphatidylcholine (PC) was used to synthesize liposomes encapsulating one lipid soluble micronutrient, vitamin E; and two water soluble micronutrients, vitamin C and iron sulfate. A commercially available PC with minimum purity of 93% was obtained and its solubility in SC-CO2 was measured at different pressure and temperature points by using a dynamic solubility measuring technique as described in our previous year's report.The obtained solubility data was furthermore used to develop a processing protocol to synthesize liposomes as a prospective drug/nutraceutical delivery system. The method involves solubilization of the lipid cargo solely in SC-CO2, followed by rapid expansion of the supercritical solution (RESS) and concomitant vacuum driven cargo loading using a venturi system (Vent-RESS),explained in our previous publications.For liposome synthesis, PC was mixed with cholesterol at a weight ratio of 5:1 at 40 °C. Cholesterol was added to PC to strengthen the rigidity of the phospholipid bilayer. For storage synthesized liposomes were collected in a TRIS buffer solution (pH=7.4). To further elucidate the feasibility of using these liposomes as bioactive carriers, two model hydrophilic (vitamin C and iron sulphate) and one lipophilic (vitamin E) bioactive micronutrients were co-encapsulated in it. Formation of liposomes was vvisualized by using a confocal laser scanning microscope (CLSM) and two different fluorescence dyes, calcein and Nile red, were used. The diameter, size distribution, and ζ-potential of the synthesized liposomes were determined by using a 90 PLUS particle size analyzer equipped with BI- ζ extension. For liposomes with and without bioactives an average diameter of 2.63 and 2.13 μm was observed. Whereas, ζ-potential values were -30.04 and -29.71 mV respectively for liposomes with and without encapsulated bioactives, indicating that stable liposomal dispersion was observed for both kind of liposomes.To measure the encapsulation efficiency (EE) of vitamin C in synthesized liposomes protamine aggregation method was used and the concentration of vitamin C was quantified by measuring the absorbance at 265 nm. A new protocol was developed to measure the EE of vitamin E, 1.5 mL of liposomal dispersion was centrifuged at 4 °C for 20 minutes at 1000xg, and the supernatant was isolated from the concentrated liposome. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was used to measure the ferrous iron content in liposome. For vitamin C, vitamin E, and iron an average EE of 77.83, 95.13, and 63.30 % was observed, respectively. Liposomes synthesized in this study demonstrated EE that is at par with other published literature. Furthermore, the simultaneous loading of three different micronutrients makes this system an appealing bioactive delivery system for the pharmaceutical and food industries. A new strategy to concentrate phospholipids from buttermilk powder was developed using a food-grade green method. The milk fat globule membrane (MFGM) phospholipids were first isolated from buttermilk powder, an undervalued dairy byproduct, by means of a sequential pure SC-CO2 and ethanol-modified SC-CO2 extraction.The highest phospholipid recovery was achieved at 60 °C, 30 MPa, and 15% (w/w) ethanol content.This sequential extraction produced a highly concentrated phospholipid extract (75%, w/w).The MFGM phospholipid concentrate had a significantly different phospholipid composition: 6.7% DHSM, 25.8% SM, 18.7% PE, 2.0% PS, 4.3% PI, and 43.7% PC. The changes in phospholipid composition can mostly be attributed to the higher solubility of PC in ethanol-modified SC-CO2 as compared to the other phospholipids, resulting in an increased percentage of PC in the MFGM phospholipid concentrate (43.7% PC) in comparison to the Folch extract (29.3% PC). Thus, this phospholipid-rich extract can be utilized in the development of functional foods as a food-grade emulsifier. Extracted MFGM concentrate was used to make liposomes by using our Vent-RESS system. Liposome synthesis was also conducted using sunflower phosphatidylcholine (SFPC) for comparison. To test the performance of the liposomes, vitamins E and C were used as model hydrophobic and hydrophilic bioactives, respectively. To study the heat stability, both MFGM and SFPC liposomes were subjected to heat treatment at three different temperatures (60, 75, and 90 °C) for 30 minutes. Post heat-treatment all samples were subjected for morphological characterization. For comparative analysis their EE%, diameter, and ζ-potential values were measured as well. In confocal micrographs for MFGM liposomes mostly presence of unilamellar vesicles (ULV) liposomes were observed; and the liposomes demonstrated an average diameter and ζ-potential values of 532.91 nm and -57.48 mV. Whereas, for SFPC a combination of: ULV, multilamellar vesicles (MLV), and multivesicular vesicles (MVV) liposomes was observed. Even though for MLV's different layers of coating materials were not observed in the micrographs but some of the synthesized liposomes possessed wall thickness substantially higher than that of the ULVs, this validates the concept of MLV formation from SFPC. For SFPC liposomes an average diameter and ζ-potential values of 761.17 nm and -36.56 mV were observed. For both MFGM and SFPC liposomes unimodal diameter distribution was observed. Stable dispersion was obtained from both MFGM and SFPC liposomes as the absolute value of ζ-potential is higher than 30 mV for both of them. However, MFGM liposomes demonstrated a substantially higher absolute value of surface charge compared to its SFPC counterpart. One possible explanation for this could be; in SFPC liposomes the negative surface charge is solely contributed by zwitterionic choline headgroups. Whereas, in MFGM liposomes, along with PC other types of phospholipids (i.e., SM, DHSM, PE, PI and PS) with higher negative charge density are present. In CLSM micrographs, it was observed that MFGM liposomes maintained their structural integrity even when heated at three different temperature levels (i.e., 60, 75 and 90 °C) for 30 minutes. No significant difference was observed in the liposomal diameter when heated at 60 °C for 30 minutes. However, the diameter of MFGM liposomes increased by a factor of 1.59 and 2.01 when heated at 75 and 90 °C, respectively. This increase in diameter can be attributed to osmotic swelling of the aqueous core enabled by the increased permeability of the phospholipid bilayer at elevated temperatures. For SFPC liposomes, disruption in liposomal structure was observed as the sample was subjected to heat treatment. For MFGM liposomes, EE of Vitamin E and C was observed to be 77.40 and 64.56%, respectively. For vitamin C no significant change was observed when liposomes were heated at a temperature of 60 °C. But EE of vitamin C dropped by factor of 1.55 and 2.40 when liposomes were heated at 75 and 90 °C. However, for vitamin E no significant change was observed in EE when liposomes were heated at 60 and 75 °C. But the EE of vitamin E for MFGM liposomes dropped by a factor of 1.39 when heated at 40 °C. SFPC liposomes demonstrated an initial EE of be 88.52 and 72.39%, for vitamin E and C, respectively. The EE values dropped significantly as the liposomes were subjected to heat treatment due to structural disintegration. The heat stability of MFGM liposomes could be attributed towards the presence of other phospholipids apart from PC in it, namely DHSM and SM, as these phospholipids possess higher transition temperature and also contribute to the heat stability of milk as an emulsion. Apart from heat stability MFGM liposomes demonstrated good shelf life as well. No significant change in EE of vitamin E and C was observed after storing the liposomal dispersion at 4 °C for 4 weeks and the respective EE was found to be 70.53 and 52.07%.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Jash,A.,Hatami T. and Rizvi, S. S. H. 2020. Phosphatidylcholine solubility in supercritical carbon dioxide: Experimental data, thermodynamic modeling, and application in bioactive-encapsulated liposome synthesis." The Journal of Supercritical Fluids 158:104720.
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Sharifi, F., Jash, A., Abbaspourrad, A. and Rizvi, S. S. H. 2020. Generation of ironized and multivitamin-loaded liposomes using venturi-based rapid expansion of a supercritical solution (Vent-RESS). Green Chemistry 22.5: 1618-1629.
- Type:
Journal Articles
Status:
Accepted
Year Published:
2020
Citation:
Ubeyitogullari, A. and Rizvi, S. S. H. 2020. Production of high-purity phospholipid concentrate from buttermilk powder using ethanol-modified supercritical carbon dioxide. J. Dairy Science. In press.
- Type:
Journal Articles
Status:
Accepted
Year Published:
2020
Citation:
Jash, A., Ubeyitogullari, A. and Rizvi, S. S. H. 2020. Synthesis of multivitamin-loaded heat stable liposomes from milk fat globule membrane phospholipids by using a supercritical-CO2 based system. Green Chemistry. In press.
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Progress 05/01/18 to 04/30/19
Outputs
Target Audience:Scientists and engineering with interest in delivery of bioactive materials. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?One post-doctoral associate, one Ph.D. student and one chemical engineering undergraduate were trained in supercritical fluid-based liposome generation technology. How have the results been disseminated to communities of interest?Through publication in scientific journals. What do you plan to do during the next reporting period to accomplish the goals? Investigate the coating mechanics of cargo loaded liposomes decorated with pH responsive double-wall of chitosan (CS) and beta-Lactoglobulin. Fortify non-fat yogurt with coated liposomes, loaded with vitamin D3 and iron, and study stability under storage at selected temperatures and evaluate pH-triggered release kinetics of bioactives cargo under simulated gastrointestinal conditions. Extraction of MFGM-phospholipid from butter fat powder by the aid of SC-CO2 and study the feasibility of using this phospholipid in liposome preparation for a pH-responsive delivery mechanism.
Impacts
What was accomplished under these goals?
The solubility of liposome carrier formulations composed ofphosphatidylcholine(PC) in supercritical-CO2(SC-CO2) was measured at three different pressures (i.e. 12.4, 13.8, and 17.2 MPa) and for each pressure level, three different system temperatures were utilized (313, 333, and 353 K).As expected, the equilibrium solubility of PC in SC-CO2increased with increasing pressure at a constant temperature and at a specific pressure it decreased with increasing temperature. The highest solubility value (0.2078 mg/g of SC-CO2) was obtained at a temperature of 313 K and 17.2 MPa pressure; which is around 2.32 times higher than the lowest solubility value (0.0931 mg/g of SC-CO2), which was observed at 353 K and 12.4 MPa. The variation of a solute's solubility in SC-CO2with changing temperature and pressure could be attributed towards two factors: solvating power of SC-CO2, which is dictated by its density; and the vapor pressure of the solute, which demonstrates an increasing pattern with increasing temperature. At a constant temperature density of SC-CO2increases with increasing pressure and this induces higher solvating capacity of SC-CO2, consequentially more dissolution of PC takes places at a higher pressure. At lower pressure region, with increasing temperature solvent density decreases and as a result solvating power of SC-CO2decreases as well. Even though the solute's vapor pressure increases with increasing temperature, the degree of increment gets overpowered by the reduction in SC-CO2density. The equilibrium solubility of PC in SC-CO2was modeled by using three different equations of state (EOS): the van der Waals-modified with Soave's approach (MvdW); Soave-Redlich-Kwong (SRK) and the Peng-Robinson (PR). To extend the application of these cubic EOSs from pure fluids to mixtures, a conventional one-parameter mixing rule was applied. The EOS parameters were converted into composition functions of pure component parameters. The solubilities of PC were predicted using the three EOSs. Experimental data were compared to the EOS predicted results. Overall, SRK EOS produced the highest accuracy results, with the average RD of 0.08%, followed by MvdW EOS (average RD = 0.11%). Ironized multivitamin loaded liposomes were generated via SC-CO2as a green solvent without using any organic solvents. The rapid expansion of supercritical solvent strategy equipped with Bernoulli's principle was employed to bring the lipophilic and hydrophilic phases in an eductor vacuum system and mix them together efficiently in a fraction of second without the aid of an external pump. In our previous research, we used the same strategy to produce glucose-loaded liposomes and studied the effect of operating and geometric parameters on the encapsulation efficiency of the cargo into the liposomes. Based on the optimized processing parameters; here, we modified the system to produce ironized multivitamin-loaded liposomes, which included four nutritional molecules: vitamin C, D3, E, and iron sulfate. The hydrophilic cargo (iron sulfate and vitamin C) were encapsulated into the core, whereas the lipophilic cargo (vitamins D3and E) were entrapped in the coating material. The liposomes were analyzed in terms of type, structure, size, surface charge, and encapsulation efficiency of the cargo in the liposomes. As coating material, soy-lecithin with two different phosphatidylcholine (PC) contents (39% and 13%) were used in this study. The lipophilic part was prepared by mixing soy lecithin, cholesterol, vitamin D3and E, in a 30:3:3:3 weight ratio. Cholesterol was added to the coating material to strengthen its rigidity. The aqueous cargo solution was composed of 0.8 M iron sulfate heptahydrate and 0.125 M ascorbic acid (vitamin C) in TRIS buffer (pH 7.4). Synthesized liposomes were collected in a buffer solution made up of ascorbic acid and iron sulfate (weight ratio 1:10). A cationic exchange resin was added to the buffer (0.1 g/mL) to separate uncoated iron sulfate. Because the oxidation of free iron sulfate in the collecting buffer leads to premature rupture of the produced liposomes. The colloidal stability of the synthesized liposomal suspension was determined by measuring its surface charge density in terms of zeta potential. Due to the presence of phosphatidylcholine in the outer layer, the synthesized liposomes are supposed to demonstrate a negative surface charge, and a higher absolute value of z-potential is synonymous to better colloidal stability. The zeta potential values were measured for the liposomes made from two different types of soy lecithin, at three different operating pressures (12, 15, and 18 MPa). The average zeta potential values were -29 mV and -40 mV for the liposomes made using coating material with PC concentrations of 13% and 39%, respectively. However, for liposomes made from a specific lecithin, no significant difference was observed in the values of zeta potential when the pressure was changed. The colloidal system would be stable as long as the absolute value of zeta potential is above 30 mV. Therefore, the liposomes made with 39% PC were in the stable range and the ones made with 13% PC were at the border. Morphological characterizations of the synthesized liposomes were conducted by using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). For CLSM, two different dyes, Fluorescein isothiocyanate (FITC)and Nile red were used to stain the core and the phospholipid bilayer parts, respectively. It was observed that when lecithin with 39% PC was used, unilamellar vesicles (ULV) and multilamellar vesicles (MLV) liposomes were created, whereas lecithin with 13% PC changed the structure of the liposomes to multivesicular vesicles (MVV). Additionally, it was observed that when the lecithin with 39% PC was mixed with the lipophilic material, i.e. cholesterol, or vitamins D3and E, the liposomes were not formed, which could be attributed towards the phase separation of the coating material (lecithin and cholesterol) and lipophilic cargo (vitamins D3and E) during their precipitation due to their supersaturation in CO2. Therefore, the lecithin with 13% PC was found to be more in line with the goals of this study, mainly because it could form liposomes when two hydrophilic and two hydrophobic cargos were involved in the process. Additionally, this type of lecithin formed MVV liposomes, which are good candidates for encapsulating hydrophilic and entrapping lipophilic cargos. Effect of operating pressure on the average size of the liposomes was measured as well. It was found that liposomes with unimodal size distribution with the average size range of 580-700 nm were formed when the SC-CO2pressure was changed from 12 MPa to 18 MPa. The vitamin (vitamins C, E, and D3) encapsulation efficiency (EE) of the synthesized liposomes was determined by using the protamine aggregation method aided with UV/Vis spectrophotometery. The absorbance values of vitamins D3, C, and E were measured at the wavelengths of 264, 265, and 295 nm, respectively. The EE values were measured for liposomes synthesized at three different pressures (12, 15, 18 MPa). The results show that the EE increased when higher pressure was used for all of the cargos. This could be attributed to the fact that SC-CO2's density increased with increasing pressure, which resulted in higher solubility of the coating material in SC-CO2. Therefore, when the concentration of the coating materials in SC-CO2increased, a higher percentage of the atomized hydrophilic cargo was coated in the eductor during the depressurization of CO2and supersaturation of the coating materials. The EE of Vitamins C, D3, E, and iron sulfate were improved to the maximum values of 54%, 54%, 60%, and 18% from 15%, 14%, 32%, and 12%, respectively when the pressure was increased from 12 MPa to 18 MPa.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Sharifi, F., Zhou, R., Lim, C., Jash, A., Abbaspourrad, A. & Rizvi, S.S.H. 2019. Generation of liposomes using a supercritical carbon dioxide eductor vacuum system: Optimization of process variables. J. CO? Utilization. 29: 163171.
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Progress 05/01/17 to 04/30/18
Outputs
Target Audience:
Nothing Reported
Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?One post-doctoral associate and an undergraduate chemical engineering student were trained in supercritical fluid technology. How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals?1. Using our high-pressure set up, determine the solubility of carrier formulations composed of milk fat globule membrane (MFGM) fraction rich phospholipids in SC-CO2and develop a predictive model using equation of state. 2. Conduct simulation studies to obtain a fundamental understanding of the effects of atomization and RESS mechanics on the size and morphology of liposomes. 3. Complete the encapsulationefficiency foriron sulfateand vitamin D3cargos for their co-delivery
Impacts
What was accomplished under these goals?
A robust, high-pressure system was set up to determine the solubility of different career materials including fat globule membrane. Simultaneously,different parameters such as expansion pressures (2.4 MPa, 13.8 MPa, and 17.2 MPa), nozzle types (converging and converging-diverging), nozzle diameters (0.5, 1.0, and 1.5 mm), and positions of the nozzle in the educatorwere studied fortheir effects on the size, uniformity, and encapsulation efficiency of resulting liposomes. In this phase of the work, glucose was encapsulated, which represents hydrophilic cargo.Theresults showed the robustness of the system that can generate liposome with the size range of 2.3-3.45 µm and 3.02-5.23 µm with the converging-diverging and converging nozzles, respectively. The size distribution of the liposomes was found to be unimodal, and their uniformity increased when the expansion pressure increased to 17.2 MPa. It was found that the converging nozzle can produce liposomes with higher encapsulation efficiency than the converging-diverging nozzle. The maximum encapsulation efficiency was 32.7% with cargo solution flow rate of 5 mL/s when the operating pressure was set at 17.2 MPa and the converging nozzle with a diameter of 1.5 mm was positioned right before the cargo introduction point.
Publications
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