Solution-enhanced Dispersion Research Articles

SUBLIMATION-BASED CUTTING-EDGE TECHNOLOGY (SUSTAINABLE DEVELOPMENT GOALS 9 and 15) TO DEVELOP CURCUMIN NANOPARTICLES BY SOLVENT-FREE GREEN CHEMISTRY METHOD FOR THEIR ANTIOXIDANT AND ANTICANCER ACTIVITY

Objective: This research aimed to develop a new, cost-effective, solvent/surfactant/supercritical carbon dioxide-free, sublimation-based method to prepare curcumin nanoparticles. The research objective was to meet Sustainable Development Goals (SDG-3,9 and 15). The problem of poor absorption of curcumin is sorted out by micro or nanonization, solid dispersion, solid solution, β-cyclodextrin complexation, micelle formation, and solution-enhanced dispersion by supercritical carbon dioxide. Methods: The curcumin, mixed with menthol, was allowed to melt at 29 °C and placed under vacuum for 6 H (h). The menthol sublimates and leaves the curcumin particles as residue. The residual curcumin particles were characterised, and stability studies were also performed. Results: The curcumin nanoparticles were stable, in the nano-size range (10-300 nm); Fourier Transform Infrared Spectroscopy (FTIR) showed the presence of CH3 and CH2 bending, aromatic C=C and C=O stretching, aromatic CC and OH stretching, aliphatic C-H bending, aromatic-OH bending with both pure curcumin and curcumin nanoparticles, that no change in bonds and groups, and differential scanning calorimetry (DSC) showed the temperature (T) =162.03, 185.64 and peak maximum is 177.986 for pure curcumin while T=164.43, 185.68 and peak maximum is 177.784 for curcumin nanoparticles that indicated compatibility between curcumin and menthol. The curcumin nanoparticles showed improved solubility, dissolution, and antioxidant activity by calculating Inhibitory Concentration50 (IC50) value 114.51 and in vitro cytotoxicity (IC50=165.6±0.084 µg/ml) of curcumin nanoparticles against MCF-7, a human breast cancer cell line with estrogen, progesterone, and glucocorticoid receptors. Conclusion: It concluded that the sublimation technique can used to prepare the nanoparticles of drugs or might be for thermo-labile drugs.

Eco-friendly encapsulation: Investigating plant-based protein-alginate shells for efficient delivery and digestion of hemp seed oil encapsulated via supercritical CO2 dispersion

In this study, supercritical carbon dioxide solution-enhanced dispersion (SEDS) was used to encapsulate hemp seed oil (HSO) within matrices of hemp seed protein isolate (HPI), pea protein (PPI) and soy protein (SPI) (0.5 % w/v) in complex with alginate (AL) (0.01 % w/v). The effects of different pH levels (3–9), NaCl concentrations (0–200 mmol/L) and simulated gastrointestinal conditions on HSO release and digestion patterns were analyzed. The findings revealed that SPI/AL microcapsules effectively maintained structural integrity and controlled oil release across diverse pH levels and salt concentrations. During gastrointestinal phases, minimal oil release was observed during oral digestion (<25 % for all samples), while significant (P < 0.05) gastric release occurred in PPI/AL (55.4 %) and SPI/AL (78.1 %) microcapsules. Surprisingly, HPI/AL microcapsules exhibited delayed and sustained release (27.9 %), indicating their potential as ideal wall material for delivering sensitive food and pharmaceutical ingredients to the intestinal stage while minimizing damage in the harsh gastric environment.

Innovative microencapsulation of hemp seed oil using plant-based biopolymers: A comparative analysis of dehydration techniques on core stability, digestibility and release pattern

This study explores various dehydration methods, including freeze drying (FD), spray drying (SD), and the supercritical carbon dioxide solution-enhanced dispersion (SEDS) process, to encapsulate hemp seed oil (HSO) within a complex matrix of hemp seed protein isolate and alginate. One noteworthy aspect of this study involves the in-depth analysis of the structural characteristics of the delivery systems, highlighting their pivotal role in shaping HSO release patterns. The findings indicate that SEDS microcapsules (SEDS-M), with their smallest particle size and smooth, spherical morphology, effectively preserved structural integrity and provided controlled oil release across diverse pH levels (3–9) and salt concentrations (0–200 mM). During the gastrointestinal phases, minimal oil release occurred during oral digestion (<25%) for all samples, while the significant gastric release occurred in FD (39.8%) and SD microcapsules (33.4%). With their highest storage stability, SEDS-M demonstrated superior delayed and sustained release (27.9%) during gastric transit, making them ideal for protecting sensitive ingredients and ensuring targeted intestinal delivery.

Advanced fabrication of complex biopolymer microcapsules via RSM-optimized supercritical carbon dioxide solution-enhanced dispersion: A comparative analysis of various microencapsulation techniques

This work aimed to enhance hemp seed oil encapsulation within a hemp seed protein-alginate complex by optimizing parameters in the solution-enhanced dispersion process, employing supercritical carbon dioxide (SEDS) without reliance on organic solvents or elevated temperatures. By response surface methodology (RSM), the microencapsulation efficacy (MEE), particle size (PS) and peroxide value (PV) was determined with respect to three parameters; temperature (°C), pressure (bar) and feed flow rate (mL/min). The optimum conditions were predicted at temperature (40 °C), pressure (150 bar) and feed flow rate (2 mL/min) to offer an MEE of 89.47%, PS of 7.81 μm and PV of 2.91 (meq/kg oil). In addition, the SEDS method was compared with spray- and freeze-drying for encapsulating hemp seed oil. The findings demonstrated SEDS' superiority, exhibiting exceptional attributes such as the highest MEE, smallest PS and the production of spherical, smooth microcapsules. This highlights its effectiveness in comparison to spray- and freeze-drying methods.

An in-depth comparative study of various plant-based protein-alginate complexes in the production of hemp seed oil microcapsules by supercritical carbon dioxide solution-enhanced dispersion

This study focuses on the microencapsulation of hemp seed oil (HSO) using a range of wall materials derived from plant-based proteins including hemp seed protein isolate (HPI), pea protein (PPI) and soy protein (SPI) in complexation with alginate (AL). The microencapsulation process was accomplished through the utilization of supercritical carbon dioxide solution-enhanced dispersion with water as a co-solvent. According to the results, both HPI/AL and PPI/AL microcapsules exhibited comparable and satisfactory properties in terms of water activity (5.26% and 5.33%), particle size (7.86 μm and 9.61 μm) and bulk density (0.363 g/mL and 0.349 g/mL). However, the overall findings highlighted the superiority of HPI/AL complex in producing microcapsules with the highest microencapsulation efficiency (90.56%), a spherical shape free from pores or fissures and an exceptional glass transition temperature. Furthermore, HPI/AL microcapsules displayed stronger antioxidant activities and oxidative stability, enhancing product shelf life significantly when compared to PPI/AL and SPI/AL microcapsules.

Encapsulation of olive leaf (Olea europaea) extract using solution-enhanced dispersion by supercritical fluids (SEDS) technique

Olive leaves are considered a byproduct or agroindustry waste, although they contain several bioactive compounds. The objective of this work was to encapsulate olive leaf extract in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) PHBV using the SEDS technique using supercritical CO2 as an antisolvent. The materials were characterized by DSC, SEM, and FTIR, and the stability (antioxidant activity, total phenolic, and total flavonoid) was monitored over time. The highest encapsulation efficiency (EE) was 86.0%. The mean particle size changed from 0.30 to 0.71 µm depending on the experimental condition. The generated particles remained stable about the residual contents of total phenolic and flavonoids in the encapsulated extract, with values greater than 70% on the 210th day. SEDS proved to be an efficient and reliable technique for the encapsulation of active olive leaf compounds in PHBV.

Particle preparation of pharmaceutical compounds using supercritical antisolvent process: current status and future perspectives.

The low aqueous solubility and subsequently slow dissolution rate, as well as the poor bioavailability of several active pharmaceutical ingredients (APIs), are major challenges in the pharmaceutical industry. In this review, the particle engineering approaches using supercritical carbon dioxide (SC CO2) as an antisolvent are critically reviewed. The different SC CO2-based antisolvent processes, such as the gas antisolvent process (GAS), supercritical antisolvent process (SAS), and a solution-enhanced dispersion system (SEDS), are described. The effect of process parameters such as temperature, pressure, solute concentration, nozzle diameter, SC CO2 flow rate, solvent type, and solution flow rate on the average particle size, particle size distribution, and particle morphology is discussed from the fundamental perspective of the SAS process. The applications of the SAS process in different formulation approaches such as solid dispersion, polymorphs, cocrystallization, inclusion complexation, and encapsulation to enhance the dissolution rate, solubility, and bioavailability are critically reviewed. This review highlights some areas where the SAS process has not been adequately explored yet. This review will be helpful to researchers working in this area or planning to explore SAS process to particle engineering approaches to tackle the challenge of low solubility and subsequently slow dissolution rate and poor bioavailability.

Dispersion of the Thermodynamically Immiscible Polypropylene and Ethylene—Propylene Triple Synthetic Rubber Polymer Blends Using Supercritical SEDS Process: Effect of Operating Parameters

In this paper, we present the results of dispersion of thermodynamically immiscible polypropylene (PP) and ethylene-propylene triple synthetic rubber (EPTSR) polymer blends using the Solution-Enhanced Dispersion by Supercritical Fluid (SEDS) technique at operation conditions in the pressure range of (8 to 25) MPa and at temperatures t = 40 °C and 60 °C. The kinetics of crystallization and phase transformation in polymer blends obtained by conventional method (melt blending) and by mixing in the SEDS process have been studied using the DSC technique. The effects of the SEDS operation process on the physical—chemical (melting temperature, heat of fusion) and mechanical (microparticle size) characteristics of the SEDS-produced polymer blends were studied.

Supercritical Fluid-Assisted Fabrication of PDA-Coated Poly (l-lactic Acid)/Curcumin Microparticles for Chemo-Photothermal Therapy of Osteosarcoma

After traditional osteosarcoma resection, recurrence of tumor is still a major clinical challenge. The combination of chemotherapy and photothermal therapy (PTT) has great potential in improving therapeutic effect. However, the studies using polydopamine (PDA) as photothermal transducing agent to improve the anti-cancer activity of curcumin (CM)-loaded poly (l-lactic acid) (PLLA) microparticles (PLLA/CM) have seldom been investigated. In this study, we reported the synthesis of PDA-coated PLLA/CM microparticles (PDA-PLLA/CM) prepared by PDA coating on the surface of the PLLA/CM microparticles fabricated by solution-enhanced dispersion by supercritical CO2 (SEDS) for chemo-photothermal therapy of osteosarcoma. The average particle sizes of PLLA/CM and PDA-PLLA/CM microparticles with a spherical shape were (802.6 ± 8.0) nm and (942.5 ± 39.5) nm, respectively. PDA-PLLA/CM microparticles exhibited pH- and near-infrared (NIR)-responsive release behavior to promote CM release in the drug delivery system. Moreover, PDA-PLLA/CM microparticles displayed good photothermal conversion ability and photothermal stability attributed to PDA coating. Additionally, the results of in vitro anti-cancer experiment showed that 500 μg/mL PDA-PLLA/CM microparticles had good anti-cancer effect on MG-63 cells and no obvious toxicity to MC3T3-E1 cells. After incubation with PDA-PLLA/CM microparticles for 2 days, NIR irradiation treatment improved the anti-cancer activity of PDA-PLLA/CM microparticles obviously and reduced the cell viability of osteosarcoma from 47.4% to 20.6%. These results indicated that PDA-PLLA/CM microparticles possessed a synergetic chemo-photothermal therapy for osteosarcoma. Therefore, this study demonstrated that PDA-PLLA/CM microparticles may be an excellent drug delivery platform for chemo-photothermal therapy of tumors.

Synthesis of curcumin and indocyanine green co-loaded PLLA microparticles via solution-enhanced dispersion using supercritical CO2 for chemo-photothermal therapy of osteosarcoma

The therapy of tumor recurrence resulting from surgical resection of osteosarcoma is still a significant challenge for clinicians. In this study, we designed curcumin (CM) and indocyanine green (ICG) co-loaded poly(L-lactic acid) (PLLA) (PLLA-CM-ICG) composite microparticles, combining photothermal therapy with chemotherapy to enhance osteosarcoma therapy synergistically. PLLA-CM-ICG microparticles of sizes of (838.3 ± 5.4) nm were prepared by solution-enhanced dispersion by a supercritical CO2 process. ICG in the PLLA-CM-ICG microparticles was more stable than free ICG. The PLLA-CM-ICG microparticles displayed pH- and near-infrared (NIR)-responsive CM release behavior. Moreover, NIR irradiation improved the anticancer activity of the PLLA-CM-ICG microparticles at a concentration of 250 μg/mL on MG-63 cells. Therefore, PLLA-CM-ICG microparticles could be employed as promising drug delivery systems for synergic photothermo-chemotherapy in osteosarcoma treatment.

Improving Solubility and Bioavailability of Breviscapine with Mesoporous Silica Nanoparticles Prepared Using Ultrasound-Assisted Solution-Enhanced Dispersion by Supercritical Fluids Method.

BackgroundBreviscapine (BRE) has significant efficacy in cardiovascular disease, but the poor water solubility of breviscapine affects its oral absorption and limits its clinical application. In this study, supercritical carbon dioxide (SCF-CO2) technology was used to improve the solubility and bioavailability of BRE loaded into mesoporous silica nanoparticles (MSNs).MethodsThe solubility of BRE in SCF-CO2 was measured under various conditions to investigate the feasibility of preparing drug-loaded MSNs by using ultrasound-assisted solution-enhanced dispersion by supercritical fluids (USEDS). The preparation process of drug-loaded MSNs was optimized using the central composite design (CCD), and the optimized preparation was comprehensively characterized. Furthermore, the drug-loaded MSNs prepared by the conventional method were compared. Finally, the dissolution and bioavailability of the preparations were evaluated by in vitro release and pharmacokinetics study.ResultsThe solubility of BRE in SCF-CO2 was extremely low which was suitable to prepare BRE-loaded MSNs by USEDS technology. The particle size of the preparation was 177.24 nm, the drug loading was 8.63%, and the specific surface area was 456.3m2/g. As compared to the conventional preparation method of solution impregnation-evaporation (SIV), the formulation prepared by USEDS technology has smaller particle size, higher drug loading, less residual solvent and better stability. The results of the in vitro release study showed that drug-loaded MSNs could significantly improve drug dissolution. The results of pharmacokinetics showed that the bioavailability of drug-loaded MSNs was increased 1.96 times compared to that of the BRE powder.ConclusionDrug-loaded MSNs can significantly improve the solubility and bioavailability of BRE, indicating a good application prospect for MSNs in improving the oral absorption of drugs. In addition, as a solid dispersion preparation technology, USEDS technology has incomparable advantages.

Spectroscopic Analysis and Dissolution Properties Study of Tosufloxacin Tosylate/Hydroxypropyl-β-Cyclodextrin Inclusion Complex Prepared by Solution-Enhanced Dispersion with Supercritical CO2

The aim of this study was to prepare tosufloxacin tosylate (TFLX) and hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complexes by solution-enhanced dispersion with supercritical CO2 (SEDS) and optimize process parameters, in vitro dissolution evaluation, and determination of inclusion sites. The effects of operating pressure, operating temperature, drug concentration, and solution flow rate on the particle size and morphology of the inclusion complex were analyzed by a single factor design experiment. The SEDS-prepared inclusion complex was characterized by TG/DSC, XRD, SEM, FT-IR, 1H NMR, 2D-ROESY, and MD and measured for in vitro dissolution, solubility, and antibacterial activity. The optimum drug concentration was 40 mg/mL and pressure 16 MPa, temperature 35 °C, and solution flow rate 1 mL/min; under this condition, the mean particle size of the inclusion complex was 1.91 μm. All characterization results confirmed the formation of an amorphous inclusion complex and the sites where TFLX and HP-β-CD bind through the H-bond were located on the aromatic B ring, pyrrolidine, and naphthyridine ring protons. Furthermore, the solubility of the inclusion complex (489.87 μg/mL) was significantly higher than that of TFLX, and the dissolution rate of TFLX increased from the initial 13.99 to 61.04% in ultrapure water. In vitro study showed that the inclusion complex maintained the antibacterial effect of TFLX. TFLX/HP-β-CD inclusion complex prepared by manipulating SEDS process conditions could significantly improve the dissolution and solubility of the water-insoluble TFLX.

Storage stability and degradation kinetics of bioactive compounds in red palm oil microcapsules produced with solution-enhanced dispersion by supercritical carbon dioxide: A comparison with the spray-drying method

Solution-enhanced dispersion by supercritical carbon dioxide (SEDS) and spray drying (SD) were used to microencapsulate red palm oil (RPO) to prolong the functionality of carotenes and vitamin E. The protective effects provided by SEDS and SD were evaluated in terms of the oxidative stability (65 °C for 35 days), fatty acid compositions, color change and degradation kinetics of carotenes and vitamin E (25 °C, 45 °C, 65 °C, and 85 °C for up to 198 days). SEDS microcapsules (SEDS-M) were the most oxidatively stable (total oxidation (Totox): 26.5), followed by SD microcapsules (SD-M) (34.9) and RPO (56.7). Degradation of carotenes and vitamin E fitted well a first-order kinetic model (average absolute relative deviation = 2–16%). SEDS-M offered better protection to vitamin E (Ea = 36 kJ/mol), whereas SD-M provided better protection for α + β carotene (Ea = 29 kJ/mol). Overall, encapsulation protected RPO during storage, with SEDS-microencapsulated RPO performing better than SD-microencapsulated RPO.

Recent Progress of Supercritical Carbon Dioxide in Producing Natural Nanomaterials.

Natural medicines are widely utilized in human healthcare. Their beneficial effects have been attributed to the existence of natural active ingredients (NAI) with a positive impact on disease treatment and prevention. Public awareness about the side effects of synthetic chemical compounds increased the need for NAI as well. Clinical applications of NAI are limited by their instability and poor water solubility, while micronization is a major strategy to overcome these drawbacks. Supercritical carbon dioxide (sc-CO2) based nano techniques have drawn great attention in nanomedicinal area for many years, due to their unique characters such as fast mass transfer, near zero surface tension, effective solvents elimination, non-toxic, non-flammable, low cost and environmentally benign. In terms of functions of sc-CO2, many modified sc-CO2 based techniques are developed to produce NAI nanoparticles with high solubility, biological availability and stability. 5 types of promising methods, including gas-assisted melting atomization, CO2-assisted nebulization with a bubble dryer, supercritical fluidassisted atomization with a hydrodynamic cavitation mixer, supercritical CO2-based coating method and solution-enhanced dispersion by sc-CO2 process, are summarized in this article followed by a highlight of their fundamental synthesis principles and important medicinal applications.

Role of polymers as crystal growth inhibitors in coprecipitation via solution-enhanced dispersion by supercritical fluids (SEDS) to improve andrographolide dissolution from standardized Andrographis paniculata extract

The poor aqueous solubility and dissolution rate of andrographolide in aqueous gastrointestinal fluids often cause low oral bioavailability. In this work, Andrographis paniculata extract containing 16% andrographolide was coprecipitated with Pluronic F127, Eudragit EPO, and Eudragit L100-55 via solution-enhanced dispersion by supercritical fluids (SEDS) to improve andrographolide dissolution in simulated intestinal fluid (pH 7.4). The SEDS working parameters were set constant as follows: 150 bar, 40 °C, CO2 flow rate 15 L/min (1 bar, 25 °C), liquid feed flow rate 0.5 mL/min, and 25 mg/mL of A. paniculata extract. SEDS coprecipitates formulated with lower Eudragit L100-55:A. paniculata mass ratios exhibited improved andrographolide dissolution in SIF (pH 7.4), while SEDS coprecipitates formulated with either Pluronic F127:A. paniculata or Eudragit EPO:A. paniculata at any mass ratio exhibited poorer andrographolide dissolution (<0.03 mg/mL released in 90 min) than SEDS-precipitated A. paniculata extract powder (0.06 mg/mL released in 90 min). In particular, SEDS coprecipitates formulated with a Eudragit L100-55:A. paniculata mass ratio of 6:25 were found to have the highest andrographolide release and dissolution rate in SIF (pH 7.4) (0.09 mg/mL released in 30 min). SEDS coprecipitation was successful, as indicated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and Fourier-transform infrared (FTIR) analysis.

Nanoparticle Formation of Puerarin-beta-Cyclodextrin Inclusion Complex Using SEDS: Dissolution Enhancement

Inclusion complex nanoparticles of puerarin and β-cyclodextrin were prepared using solution-enhanced dispersion by supercritical fluids to improve the dissolution rate of puerarin. The factors that influenced particle size and inclusion yield such as, pressure, temperature, flow rate of CO2, and flow rate of the solution, were investigated. Scanning electron microscopy, X-ray diffraction and Fourier-transform infrared spectroscopy were used to characterize the products. Release behavior of inclusion complex nanoparticles of puerarin was also studied. Elevated temperatures increased the inclusion yield. Elevated pressures reduced the particle size. Scanning electron microscopy, X-ray diffraction and Fourier-transform infrared spectroscopy confirmed the formation of inclusion complex nanoparticles of puerarin. The accumulated release rate of inclusion complex nanoparticles of puerarin reached 98 % within 5 min, markedly higher than that of the puerarin powder and its physical mixture. Inclusion complex nanoparticles of puerarin prepared by solution-enhanced dispersion by supercritical fluids can greatly improve the in vitro release of puerarin.

Crystallization of Polymer Mixtures in the Course of Their Solution-Enhanced Dispersion by Supercritical Fluids

The characteristics of phase equilibria for systems including toluene, supercritical CO2, and ethylene–vinyl acetate copolymers (EVACs) were studied experimentally. Solution enhanced co-dispersion of EVAC and low-density polyethylene mixtures by supercritical fluids (SEDS) was performed under pressures of 8.0–25.0 MPa at 313, 323, and 333 K. The comparison of melting and crystallization in the resulting copolymer mixtures with those in the same-composition mixtures obtained by melt mixing showed SEDS to result in an increase in the degree of crystallinity of the polymer mixtures.

Precise Dissolution Control and Bioavailability Evaluation for Insoluble Drug Berberine via a Polymeric Particle Prepared Using Supercritical CO₂.

It is still controversial whether poor aqueous solubility is the most primary reason for the low oral bioavailability of insoluble drugs. Therefore, in this study, berberine-loaded solid polymeric particles (BPs) of varied dissolution profiles with β-cyclodextrin (β-CD) as carrier were fabricated using solution-enhanced dispersion by supercritical fluids (SEDS), and the relationship between dissolution and berberine (BBR) bioavailability was evaluated. Dissolution property was controlled via particle morphology manipulation, which was achieved by adjusting several key operating parameters during the SEDS process. Characterization on BP using infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction indicated that BBR was dispersed in amorphous form, while nuclear magnetic resonance spectroscopy showed that methoxy groups of BBR were included into the cavities of β-CD. In vivo pharmacokinetic studies showed that oral bioavailability increased by about 54% and 86% when the dissolution rate of BBR was increased by 51% and 83%, respectively. The entry speed of BBR into the bloodstream was also advanced with the degree of dissolution enhancement. It seemed that dissolution enhancement gave positive effect to the oral bioavailability of berberine, but this might not be the crucial point. Meanwhile, supercritical CO2 technology is a promising method for pharmaceutical research due to its advantages in regulating drug-dosage properties.

Solution-enhanced dispersion by supercritical fluids: an ecofriendly nanonization approach for processing biomaterials and pharmaceutical compounds.

In recent years, the supercritical fluid (SCF) technology has attracted enormous interest from researchers over the traditional pharmaceutical manufacturing strategies due to the environmentally benign nature and economically promising character of SCFs. Among all the SCF-assisted processes for particle formation, the solution-enhanced dispersion by supercritical fluids (SEDS) process is perhaps one of the most efficient methods to fabricate the biomaterials and pharmaceutical compounds at an arbitrary gauge, ranging from micro- to nanoscale. The resultant miniature-sized particles from the SEDS process offer enhanced features concerning their physical attributes such as bioavailability enhancement due to their high surface area. First, we provide a brief description of SCFs and their behavior as an anti-solvent in SCF-assisted processing. Then, we aim to give a brief overview of the SEDS process as well as its modified prototypes, highlighting the pros and cons of the particular modification. We then emphasize the effects of various processing constraints such as temperature, pressure, SCF as well as organic solvents (if used) and their flow rates, and the concentration of drug/polymer, among others, on particle formation with respect to the particle size distribution, precipitation yield, and morphologic attributes. Next, we aim to systematically discuss the application of the SEDS technique in producing therapeutic nano-sized formulations by operating the drugs alone or in combination with the biodegradable polymers for the application focusing oral, pulmonary, and transdermal as well as implantable delivery with a set of examples. We finally summarize with perspectives.

Nanoparticle formation of PVP/astaxanthin inclusion complex by solution-enhanced dispersion by supercritical fluids (SEDS): Effect of PVP and astaxanthin Z-isomer content

The effects of operating conditions and Z-isomer content of astaxanthin on coprecipitate formation of polyvinylpyrrolidone (PVP) and astaxanthin by solution-enhanced dispersion by supercritical fluids (SEDS) process were investigated. Using this process, nano-sized (100–200 nm) and water-soluble PVP/astaxanthin inclusion complex was successfully prepared. As the operating pressure increased from 8 to 15 MPa at a constant temperature, astaxanthin content in the coprecipitates decreased, and increasing the operating temperature from 40 to 60 °C at a constant pressure, the particle size and the astaxanthin content increased. Increasing the PVP ratio for astaxanthin in the range of 5:1 to 20:1, the particle size decreased and when 10:1 of the ratio, the astaxanthin content in the coprecipitates was the highest (60 °C, 10 MPa). Additionally, as the Z-isomer content of astaxanthin increased, the astaxanthin content decreased slightly. However, the coprecipitates rich in astaxanthin Z-isomers, which have higher bioavailability and antioxidant capacity, were obtained.