Albumin Nanoparticles Research Articles

Drug-Loaded Albumin Nanoparticles: A Short Review

Albumin is derived from plasma and it is the most abundant protein in plasma, which is an ideal material for the preparation of nanoparticles because of its good biocompatibility, noncytotoxicity, nonimmunogenicity, biodegradability, and so on. Albumin amplifies the targeting of drugs, brings down the deadliness of free drugs, and amplifies water solubility of free drugs. The methods of preparation of albumin nanoparticles exhibit benefits and drawbacks due to contrasts in principles and preparation conditions.

Fabrication of Doxorubicin Nanoparticles Mediated by Folic Acid and Its Effect on the Wnt/β-Catenin Signaling to Improve Precancerous Lesions in Gastric Cancer

Doxorubicin hydrochloride (DOX) is an anthracycline broad-spectrum antitumor drug, but it can produce a wide range of cytotoxicities in the body. Intravenous injection of a high dose of DOX causes serious toxicity and side effects in the heart and spinal cord. These shortcomings limit the clinical adoption of DOX. In this work, folic acid was coupled to DOX albumin nanoparticles (NPs) by chemical modification so that the preparation could actively target tumor site accumulation and release DOX to inhibit tumor cells. Albumin NPs were prepared by the desolvation method, and the formulation and preparation process were optimized. The particle size and granularity were taken as evaluation indexes. The in vitro antitumor activity of folic acid-mediated DOX albumin NPs against human hepatoma cell HepG2 and human gastric cancer cell SGC7901 was evaluated by using the methyl tetrazolium (MTT) assay with commercial DOX as a reference. Twenty SD rats were utilized to participate in the efficacy analysis of folic acid-mediated DOX albumin NPs for gastric precancerous lesions (GPLs). The results showed that the average particle size of folate-mediated doxorubicin albumin NPs was 267.28±0.38 nm, and 90% of them were less than 280.00 nm, showing a uniform particle size distribution. The drug release rate of the NPs within 24 h was 27.3%, and the NPs had sustained release properties. The IC50 values of the NPs and DOX aqueous solution on the highly expressed HepG2 cells were 4.78 μmol/L and 5.26 μmol/L, respectively, and those on the SGC7901 cells were 4.62 μmol/L and 5.06 μmol/L, respectively. After the establishment of the GPL model, the gene levels in the Wnt/β-catenin signaling were markedly upregulated (P <0.05). Folic acid-mediated doxorubicin albumin NPs greatly inhibited the abnormal expression of the above genes (P <0.01), i.e., they could effectively prevent further precancerous lesions of gastric cancer.

Bacteria engineered with intracellular and extracellular nanomaterials for hierarchical modulation of antitumor immune responses.

Induction of immunogenic cell death (ICD) by hyperthermia can initiate adaptive immune responses, emerging as an attractive strategy for tumor immunotherapy. However, ICD can induce proinflammatory factor interferon-γ (IFN-γ) production, leading to indoleamine 2,3-dioxygenase 1 (IDO-1) activation and an immunosuppressive tumor microenvironment, which dramatically reduces the ICD-triggered immunotherapeutic efficacy. Herein, we developed a bacteria-nanomaterial hybrid system (CuSVNP20009NB) to systematically modulate the tumor immune microenvironment and improve tumor immunotherapy. Attenuated Salmonella typhimurium (VNP20009) that can chemotactically migrate to the hypoxic area of the tumor and repolarize tumor-associated macrophages (TAMs) was employed to intracellularly biosynthesize copper sulfide nanomaterials (CuS NMs) and extracellularly hitchhike NLG919-embedded and glutathione (GSH)-responsive albumin nanoparticles (NB NPs), forming CuSVNP20009NB. After intravenous injection into B16F1 tumor-bearing mice, CuSVNP20009NB could accumulate in tumor tissues and repolarize TAMs from the immunosuppressive M2 to immunostimulatory M1 phenotype and release NLG919 from extracellular NB NPs to inhibit IDO-1 activity. Under further near infrared laser irradiation, intracellular CuS NMs of CuSVNP20009NB could photothermally induce ICD including calreticulin (CRT) expression and high mobility group box 1 (HMGB-1) release, promoting intratumoral infiltration of cytotoxic T lymphocytes. Finally, CuSVNP20009NB with excellent biocompatibility could systematically augment immune responses and significantly inhibit tumor growth, holding great promise for tumor therapy.

Phospholipid-based nanodrill technology for enhanced intracellular delivery of nano-sized cargos

Nanosized drug delivery systems typically enter the cell via endocytosis. However, a significant amount of the endocytosed cargo cannot effectively escape from the endosome, resulting in drug degradation. Therefore, there are several ongoing efforts to develop transmembrane delivery systems that could circumvent endocytosis. In this study, phospholipid nanotube nanodrills (LDs) were formed onto the surface of a human serum albumin nanoparticle via self-assembling phospholipids. The nanodrill technology enhanced the intracellular uptake efficiency of nanoparticles via energy-independent direct cell membrane permeation. The length of the nanodrills according to the DSPE-PEG to DSPC ratio was investigated both experimentally and theoretically. Our findings demonstrated that longer nanodrills were formed on the surface of the nanoparticles as the ratio of DSPC (i.e., a strongly hydrophobic lipid) in the two phospholipids increases. Moreover, the intracellular uptake efficiency increased as the length of phospholipid nanodrills increased. In addition to enhancing intracellular delivery, the phospholipid nanodrills could penetrate the extracellular matrix and enable the introduction of nanoparticles, thus highlighting the promising tissue penetration capacity of phospholipid nanodrill technology. The improved cell permeability of LD technology was demonstrated by effectively inhibiting specific genes via siRNA-based therapeutic delivery. Moreover, this approach enhanced the efficacy of chemotherapeutics against chemo-resistant cancer cells. Therefore, LD technology could be used to deliver genetic materials and chemical-based therapeutics both in vitro and in vivo.

Use of nanoparticles in animal models for prostate cancer treatment: a systematic review.

To conduct a systematic review of nanoparticles' use in the treatment of prostate cancer in animals. A systematic review was conducted in the databases PubMed, Scientific Electronic Library Online (SciELO), Latin American and Caribbean Health Sciences Literature (LILACS), Cochrane Library, and EMBASE, and the descriptors were chosen based on terms indexed in Health Sciences Descriptors (DeCS)/Medical Subject Headings (MESH), which are: nanoparticles, nanomedicine, and prostate cancer. The systematic review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with ID CRD42021271008. A total of 3,897 articles was chosen; after reading the inclusion and exclusion criteria, six scientific articles with themes involving nanoparticles carrying medications were reached. Among the nanoparticles found, there were carboxymethylcellulose polymer, micellar casein nanoparticles, liquid crystal nanoparticles, serum albumin nanoparticles, and poly(ethylene glycol)-block-polylactide (mPEG-PLA) conjugated nanoparticles encapsulating cabazitaxel, docetaxel, and flutamide, which were nanoparticles used to treat prostate cancer in animals. Through using nanoparticles to encapsulate medications for treating prostate cancer in animals, studies show a decrease in weight and tumor reduction, with nanoparticles resulting in greater survival time than free medications. The improved permeability and retention effect of nanoparticles in the bloodstream contribute to their effectiveness.

Nanoparticles based composite coatings with tunable vascular endothelial growth factor and bone morphogenetic protein-2 release for bone regeneration.

Bone healing is a complex cascade involving precisely coordinated spatiotemporal presentation of multiple growth factors (GFs), including osteogenic and angiogenic GFs, and each stage of bone healing requires varying types and content of GFs. In this study, we fabricated a composite nanocoating with tunable vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) that was coated on the surface of a polydopamine (PDA)-decorated tertiary calcium phosphate (TCP) scaffold using VEGF-loaded chitosan/bovine serum albumin nanoparticles (CS/BSA-NPs) and BMP-2-loaded poly-L-lysine/oxidized alginate nanoparticles (PLL/OALG-NPs). It was found that VEGF could be efficiently released to promote vascularization in early bone repair stages due to the rapid biodegradation of CS/BSA-NPs, while bone formation can be promoted by a sustained release of BMP-2 from the slowly degrading PLL/OALG-NPs. The composite coating and TCP scaffold can be conjugated due to the excellent adhesive property of PDA. The composite coating can achieve the rapid release of VEGF and sustained release of BMP-2, which can activate GFs for accelerating bone healing.

BSA-AIE Nanoparticles with Boosted ROS Generation for Immunogenic Cell Death Immunotherapy of Multiple Myeloma.

The main obstacle of multiple myeloma (MM) therapy is the compromised immune microenvironment, which leads to MM relapses and extramedullary disease progression. In this study, a novel strategy is reported of enhanced immunogenic cell death (ICD) immunotherapy with aggregation-induced emission (AIE) photosensitizer-loaded bovine serum albumin (BSA) nanoparticles (referred as BSA/TPA-Erdn), which can activate T cells, convert the cold tumor to hot, and reverse T cell senescence to restore the immune microenvironment for MM treatment. Loading AIE photosensitizer into the hydrophobic domain of BSA proteins significantly immobilizes the molecular geometry, which massively increases reactive oxygen species (ROS) generation and elicits a promising ICD immune response. Employing a NOD-SCID IL-2receptor gamma null mice model with MM patients' monocytes, it is shown that BSA/TPA-Erdn can simulate human dentric cell maturation, activate functional T lymphocytes, and increase additional polarization and differentiation signals to deliver a promising immunotherapy performance. Intriguingly, for the first time, it is shown that BSA/TPA-Erdn can greatly reverse T cell senescence, a main challenge in treating MM. Additionally, BSA/TPA-Erdn can effectively recruit more functional T lymphocytes into MM tumor. As a consequence, BSA/TPA-Erdn restores MM immune microenvironment and shows the best MM tumor eradication performance, which shall pave new insights for MM treatment in clinical practices.

The Loading of Epigallocatechin Gallate on Bovine Serum Albumin and Pullulan-Based Nanoparticles as Effective Antioxidant.

Due to its poor stability and rapid metabolism, the biological activity and absorption of epigallocatechin gallate (EGCG) is limited. In this work, EGCG-loaded bovine serum albumin (BSA)/pullulan (PUL) nanoparticles (BPENs) were successfully fabricated via self-assembly. This assembly was driven by hydrogen bonding, which provided the desired EGCG loading efficiency, high stability, and a strong antioxidant capacity. The encapsulation efficiency of the BPENs was above 99.0%. BPENs have high antioxidant activity in vitro, and, in this study, their antioxidant capacity increased with an increase in the EGCG concentration. The in vitro release assays showed that the BPENs were released continuously over 6 h. The Fourier transform infrared spectra (FTIR) analysis indicated the presence of hydrogen bonding, hydrophobic interactions, and electrostatic interactions, which were the driving forces for the formation of the EGCG carrier nanoparticles. Furthermore, the transmission electron microscope (TEM) images demonstrated that the BSA/PUL-based nanoparticles (BPNs) and BPENs both exhibited regular spherical particles. In conclusion, BPENs are good delivery carriers for enhancing the stability and antioxidant activity of EGCG.

Effect of folate-targeted Erlotinib loaded human serum albumin nanoparticles on tumor size and survival rate in a rat model of glioblastoma

The aim of this study was to prepare folate-targeted Erlotinib loaded human serum albumin nanoparticles (FA-ERL-HSA NPs) and investigate in vitro cytotoxic and apoptotic effects using cell lines (U87MG and C6 cells) and an in vivo rat bearing C6 glioma model. The mean size of the FA-ERL-HSA NPs prepared using a desolvation method was 135 nm. In vitro MTT assays demonstrated that FA-ERL-HSA NPs had an IC50 value of 52.18 μg/mL and 17.53 μg/mL compared to free ERL which had an IC50 value of 119.8 μg/mL and 103.2 μg/mL for U87MG and C6 cells for 72 h, respectively. Flow cytometry results showed the apoptosis rate with FA-ERL-HSA NPs (100 μg/mL, 72 h) was higher compared to free ERL for both U87MG and C6 cells. Experiments using a rat glioblastoma model via TUNEL assay indicated that the apoptosis index of FA-ERL-HSA NPs was 48 % compared to 21 % for free ERL and the tumor size effectively decreased after a daily injection of 220 μg (2.5 mg/kg) from 87.45 mm3 (19th day) to 1.28 mm3 (60th day). The median survival rate of the rats increased after treatment to >100 days which was greater than controls.

PEGylation of genistein-loaded bovine serum albumin nanoparticles and its effect on in vitro cell viability and genotoxicity properties

Self-assembled bovine serum albumin nanoparticles loaded with the isoflavone genistein have shown apoptosis-mediated cytotoxicity against murine mammary adenocarcinoma F3II cells. Due to their protein nature and small particle size (13–15 nm), their parenteral administration could be affected by possible immunogenic reactions and rapid clearance from the bloodstream. To avoid these problems, PEGylation of the systems was achieved in this work by using a 30 kDa methoxy-polyethylene glycol carbonyl imidazole derivative through the reaction between the carbonyl imidazole group and the amino groups of Lys residues on the protein surface, which was confirmed by a 17% reduction in the available amino groups content measured by the o-phthaldialdehyde method. PEGylated isoforms were obtained, showing an increase of particle size from 13 to 15 nm to around 260 nm, and were purified by SEC-FPLC and characterized by SDS-PAGE, DLS and AFM techniques. The effect of PEGylation on BSAnp-Gen cytotoxicity and genotoxicity against F3II cells was evaluated in vitro by MTT assay, flow cytometry analysis and micronucleus assay. From the results, PEGylation produced an improvement of the biological properties of genistein-loaded nanoparticles in terms of cytotoxicity (lower IC50), not affecting the induction of apoptosis, decreasing the genotoxicity of the systems (less induction of micronucleus formation).

Co-delivery of ibrutinib and hydroxychloroquine by albumin nanoparticles for enhanced chemotherapy of glioma

Ibrutinib (IBR) is an oral covalent inhibitor of Bruton’s tyrosine kinase (BTK) that has been approved for the treatment of hematological malignancies. It was reported that IBR exhibited great therapeutic potential for glioma. However, the poor water solubility and high hepatic first-pass effect restrict its anti-glioma application. Meanwhile, IBR induces cytoprotective autophagy through Akt/mTOR signaling pathway, thus leading to a compromised antitumor effect. Herein, we aimed to develop a human serum albumin (HSA) based co-delivery system (IBR&HCQ HSA NPs) encapsulating IBR and hydroxychloroquine (HCQ). The bioavailability of IBR was largely improved, and enhanced sensitivity of glioma to IBR was achieved due to inhibition effect of HCQ on IBR-induced pro-survival autophagy. The physicochemical properties of IBR&HCQ HSA NPs were characterized to optimize the formulation. Biodistribution investigation revealed that HSA NPs (20 mg/kg, i.v.) dramatically increased the accumulation of IBR in glioma, which was 5.59 times higher than that of free IBR (100 mg/kg, i.g.). CCK-8 and apoptosis assays demonstrated that IBR&HCQ HSA NPs showed maximal cytotoxicity to C6 cells. In vivo studies indicated that the survival time was significantly prolonged in IBR&HCQ HSA NPs treated mice compared to those treated with IBR HSA NPs. Taken together, the HSA-based drug delivery system of IBR and HCQ opens a new avenue for efficient treatment of glioma.

Pharmacometabolomic assessment of vitamin E loaded human serum albumin nanoparticles on HepG2 cancer cell lines

Pharmacometabolomics is a novel metabolomics tool to provide information about how a subject will respond to drug treatment in metabolome level. In this study, a Q-TOF LC/MS based untargeted metabolomics approach was performed to evaluate the metabolomic profile change on HepG2 hepatocellular carcinoma cells treated with vitamin E in free form, vitamin E loaded in human serum albumin nanoparticles, and blank nanoparticles.Vitamin E loaded human serum albumin nanoparticles, and blank nanoparticles were prepared and characterized with particle size distribution, surface charge and cytotoxicity against L929 and HepG2 cell lines. The metabolite and lipid fractions of the cells treated with vitamin E, vitamin E loaded human serum albumin nanoparticles, and blank nanoparticles were analyzed using Q-TOF LC/MS. XCMS and MetaboAnalyst 5.0 were used to process the data and identify the peaks. Principal component analysis (PCA) was performed to visualize the differences between groups.Totally 247 peaks for metabolites and 788 peaks for lipid were found to be statistically in different ratios (p < 0.05 and fold change >1.5) between groups. Some metabolites (histidine, aspartylglycosamine, glutathione, prostaglandin, alpha-tocotrienol, urobilinogen, coproporphyrinogen, and glucosylceramide) involved in liver activity and/or known as diagnostic and prognostic biomarker(s) were the effected ones upon Vitamin E treatment.The metabolomic profiles for vitamin E loaded human serum albumin nanoparticles treated cells were different than the ones treated with vitamin E alone. This study concluded that both vitamin E and vitamin E loaded human serum albumin nanoparticles may provide effects on liver regeneration pathways but with different responses. According to the results in the present study, it can be considered that the pharmacometabolomics profile of the nanoparticle-based drug delivery for vitamin E can be different in clinical practice.

Evaluation of the hepatoprotective effect of naringenin loaded nanoparticles against acetaminophen overdose toxicity

Acute liver injury is a common clinical disease, which easily leads to liver failure and endangers life, seriously threatening human health. Naringenin is a natural flavonoid that holds therapeutic potential against various liver injuries; however it has poor water solubility and bioavailability. In this study, we aimed to develop naringenin-loaded bovine serum albumin nanoparticles (NGNPs) and to evaluate their hepatoprotective effect and underlying mechanisms against acetaminophen overdose toxicity. In vitro data indicated that NGNPs significantly increased the drug solubility and also more effectively protected the hepatocyte cells from oxidative damage during hydrogen peroxide exposure or lipopolysaccharide (LPS) stimulation. In vivo results confirmed that NGNPs showed an enhanced accumulation in the liver tissue. In the murine model of acetaminophen-induced hepatotoxicity, NGNPs could effectively alleviate the progression of acute liver injury by reducing drug overdose-induced levels of oxidative stress, inflammation and apoptosis in hepatocytes. In conclusion, NGNPs has strong hepatoprotective effects against acetaminophen induced acute liver injury.

Chitosan-coated bovine serum albumin nanocarriers mediate efficient delivery of methotrexate in breast cancer therapeutics

Methotrexate (MTX) is highly investigated for the treatment of various malignancies, including breast cancer. However, its use is limited because of its drawbacks related to high toxicity, poor solubility, and permeability as well as short plasma half-life. Therefore, in this study, we suggested MTX-loaded novel protein and polysaccharide-based nanovehicles in order to enhance the effect of MTX for breast cancer treatment. We prepared MTX-loaded uncoated and chitosan-coated bovine serum albumin (BSA) nanoparticles and characterized by particle size and distribution, surface charge, encapsulation efficiency and morphological structure. Furthermore, we compared the cellular uptake, cytotoxic effect and apoptosis induction properties of free MTX, MTX-loaded uncoated and chitosan-coated BSA nanoparticles on MCF-7 breast cancer cells. The chitosan-coating turned the surface charge of the uncoated BSA nanoparticles from −25.5 mV up to 53.3 mV and the cellular uptake performances of nanoparticles were significantly changed according to the surface charge of nanoparticles. The positively charged chitosan-coated nanoparticles were more efficiently internalized than negatively charged uncoated BSA nanoparticles. Besides, in line with cellular uptake experiments, the cytotoxic effect as well as apoptosis induction properties of chitosan-coated BSA nanoparticles were found to be greater than both uncoated BSA nanoparticles and free MTX. The analyses showed that the MCF7 cell viability was decreased to 58 and 35% at the end of 48-h treatment at 5 μg mL−1 dose MTX by uncoated and coated BSA nanoparticles, respectively. Moreover, chitosan-coated BSA nanoparticles lead to 3.67- and 2.23-folds higher apoptosis-related cellular death than that of free drug and uncoated nanoparticles, respectively. Based on our findings, the designed MTX-loaded chitosan-coated BSA nanoparticles can be suggested as a novel and efficient strategy for the treatment of breast cancer.

Preparation, physicochemical characterization, and bioactivity evaluation of berberine-entrapped albumin nanoparticles

Berberine (BBR) is an isoquinoline alkaloid with several clinical therapeutic applications. Its low water solubility, absorption, and cellular bioavailability diminish BBR's therapeutic efficacy. In this study, BBR was encapsulated into bovine serum albumin nanoparticles (BSA NPs) core to reduce BBR limitations and enhance its clinical therapeutic properties. Several physicochemical characterization tools, such as Dynamic Light Scattering and Ultraviolet–Visible spectroscopic measurements, field emission transmission electron microscopy surface morphology, Fourier transforms infrared spectroscopy, thermal stability analysis, and releasing studies, were used to evaluate the BBR-BSA NPs. Compared to BBR, BBR-BSA nanoparticles demonstrated superior free radical scavenging and antioxidant capacities, anti-hemolytic and anticoagulant efficacies, and antimicrobial activities, as demonstrated by the findings of the in vitro studies. Furthermore, a stressed pancreatic rat model was induced using a high-fat, high-sucrose diet plus carbon tetrachloride injection. The in vivo results revealed that BBR-BSA NPs substantially restored peripheral glucose metabolism and insulin sensitivity. Oral administration of BBR-BSA NPs also improved pancreatic β-cells homeostasis, upregulated pancreatic antioxidant mechanisms, inhibited oxidants generation, and attenuated oxidative injury in the stressed pancreatic tissues. In conclusion, our in vitro and in vivo results confirmed that BBR-BSA NPs demonstrated more potent antioxidant properties and restored pancreatic homeostasis compared to BBR.

Corrigendum: Characterization of Water Solubility and Binding of Spin Labeled Drugs in the Presence of Albumin Nanoparticles and Proteins by Electron Paramagnetic Resonance Spectroscopy

Corrigendum: Characterization of Water Solubility and Binding of Spin Labeled Drugs in the Presence of Albumin Nanoparticles and Proteins by Electron Paramagnetic Resonance Spectroscopy

Synthesis of albumin nanoparticles in a water-miscible ionic liquid system, and their applications for chlorambucil delivery to cancer cells

Serum albumin has been a preferred protein to generate biodegradable and non-toxic nanoparticles (NPs) for drug delivery applications. Different methods applied for the preparation of serum albumin NPs mostly used organic solvents. Here, we prepared serum albumin NPs in an ionic liquid (IL) system. ILs are considered to be green and designer solvents with unique properties that can replace organic solvents in the synthesis of albumin NPs. Bovine serum albumin (BSA) proteins dissolved in water were transformed into BSA NPs in a water/ Triton™X (TX-100), 1-butanol/1-butyl-3-methylimidazolium trifluoromethanesulfonate (BmimCF3SO3) microemulsion-like system by using a high-speed homogenizer and crosslinker glutaraldehyde. The obtained BSA NPs have been used in drug loading and release studies with a hydrophobic anticancer drug chlorambucil (Chl). Drug loading increased as increasing the ratio of Chl incubated with BSA NPs. Monitoring the drug release by UV–Vis spectroscopy revealed a burst release at first 4 h, but two-thirds of drugs stayed with NPs upon diffusion method. On the other hand, cellular uptake of Chl loaded BSA NPs caused a significant MCF7 breast cancer cell death, whereas free Chl and unloaded BSA NPs did not have a significant effect on the cell viability. Furthermore, in vivo toxicity assessment of BSA NPs obtained in the IL system was conducted in the zebrafish animal model. It showed that zebrafish body is able to eliminate BSA NPs without any toxic side effects and encapsulation of Chl into NPs reduced the toxicity of free Chl. In summary, we showed that BSA NPs with size smaller than 200 nm could be prepared in BmimCF3SO3 mediated system. They can be used for Chl loading (up to 6.9 wt%) with a sustainable release and they induce significant cell death in Chl sensitive cancer cells up to 45% in 24 h. These results indicate that BSA NPs could be prepared alternatively in IL systems and used in drug delivery studies.

Increased blood-brain barrier permeability of neuroprotective drug by colloidal serum albumin carriers

Encapsulation possibilities of two neuroprotective drugs of slightly different structures, kynurenic acid (KYNA) and its more hydrophilic analogue (SzR72), are studied in bovine serum albumin (BSA) nanoparticles (NPs) to increase their permeability through the blood-brain barrier (BBB). The effect of various preparation conditions such as protein concentration, protein-to-drug ratio, pH, ionic strength, type, and amount of desolvation agent and cross-linker concentration are discussed. It was found that the encapsulation proved to be successful only if the drugs are added to the pre-prepared BSA NPs. If the pH of the medium is adjusted to 4.0 instead of 7.4 the drug loading increased (from 4.5 % to 20.7 % for KYNA) due to the electrostatic interaction between the oppositely charged functional groups accompanied by significant secondary structural changes verified by circular dichroism spectroscopy (CD) suggesting the drug insertion in the hydrophobic pockets of BSA. The in vitro polar brain lipid extract (porcine) based permeability test proved the aimed three-, or fourfold higher BBB specific penetration for KYNA in the carrier relative to the unformatted drug.

Generation of curcumin-loaded albumin nanoparticles by using off-the-shelf microfluidics driven by gravity

The generation albumin-based nanocarriers by precipitation from solution has great interest in the formulation of advanced nutritional products. Microfluidic techniques enable the implementation of low energy and continuum processes, with fast mass transfer and homogeneous mixing at the microscale. Here we describe the microfluidic generation of curcumin-loaded alpha lactalbumin nanoparticles in a simple and inexpensive way, by using off-the-shelf devices designed to produce solvent-shifting nanoprecipitation in core-sheath flows driven by gravity, which has not been reported before. Nanoparticles were characterized by dynamic light scattering, electron microscopy, and infrared spectroscopy. The microfluidic operating conditions were defined by theory and experiments, and the critical parameters controlling the nanoparticles diameter were identified. The prepared nanoparticles resulted practically monodisperse, the curcumin entrapment efficiency was about 40 %, and almost 70 % of the bioactive was gradually delivered in release experiments. The proposed methodology is a promising route to scale up the microfluidic elaboration of nanoparticles for the entrapment of active ingredients.

Lyophilization of Curcumin-Albumin Nanoplex with Sucrose as Cryoprotectant: Aqueous Reconstitution, Dissolution, Kinetic Solubility, and Physicochemical Stability.

An amorphous curcumin (CUR) and bovine serum albumin (BSA) nanoparticle complex (nanoplex) was previously developed as a promising anticancer nanotherapy. The CUR-BSA nanoplex had been characterized in its aqueous suspension form. The present work developed a dry-powder form of the CUR-BSA nanoplex by lyophilization using sucrose as a cryoprotectant. The cryoprotective activity of sucrose was examined at sucrose mass fractions of 33.33, 50.00, and 66.66% by evaluating the lyophilized nanoplex’s (1) aqueous reconstitution and (2) CUR dissolution and kinetic solubility. The physicochemical stabilizing effects of sucrose upon the nanoplex’s 30-day exposures to 40 °C and 75% relative humidity were examined from (i) aqueous reconstitution, (ii) CUR dissolution, (iii) CUR and BSA payloads, (iv) amorphous form stability, and (v) BSA’s structural integrity. The good cryoprotective activity of sucrose was evidenced by the preserved BSA’s integrity and good aqueous reconstitution, resulting in a fast CUR dissolution rate and a high kinetic solubility (≈5–9× thermodynamic solubility), similar to the nanoplex suspension. While the aqueous reconstitution, CUR dissolution, and amorphous form were minimally affected by the elevated heat and humidity exposures, the treated nanoplex exhibited a lower BSA payload (≈7–26% loss) and increased protein aggregation postexposure. The adverse effects on the BSA payload and aggregation were minimized at higher sucrose mass fractions.