Polymerized Albumin Research Articles

Physicochemical Stability of Nab-Paclitaxel (Pazenir) Infusion Dispersions in Original Glass Vials and EVA Infusion Bags

Background/Objectives: The study objective was to determine the physicochemical stability of nab-paclitaxel (Pazenir) ready-to-use (RTU) dispersion for infusion in original glass vials and ready-to-administer (RTA) infusion dispersion in EVA infusion bags. Methods: Triplicate test dispersions were prepared and stored light protected for a maximum of 28 days either in the original glass vials (RTU) at 2–8 °C or in EVA infusion bags (RTA) at 2–8 °C and at 25 °C. Directly after reconstitution and on days 1, 3, 5, 7, 14, 21, and 28 samples were withdrawn and paclitaxel concentrations assayed by a stability-indicating HPLC method. In parallel, pH and osmolality were measured. In a second series, test dispersions were stored over a 14-day period and inspected daily for visible particles and colour changes. Samples were taken daily for particle size analysis. Integrity and particle size distribution of the nanoparticles were determined by dynamic light scattering (DLS) and albumin monomers, dimers, oligomers, or polymers by size-exclusion-chromatography (SEC). Results: Non-redispersible particles were observed in test dispersions on day 5 (RTA 25 °C), day 7 (RTA 2–8 °C), and day 11 (RTU 2–8 °C). DLS analysis revealed out-of-specification results for the polydispersity index from day 7 (RTA 25 °C) and day 12 (RTU, RTA refrigerated). Paclitaxel concentrations remained >95% of the initial concentrations for 7 days (RTU 2–8 °C, RTA 25 °C) and for 14 days (RTA 2–8 °C). All test dispersions met the specifications regarding the oligomeric status of albumin, pH, and osmolality over the investigation periods. Conclusions: Stability of nab-paclitaxel dispersions is limited by the release of water-insoluble paclitaxel from the nanoparticles and subsequent crystallisation and by formation of insoluble albumin aggregates. Based on our overall results, shelf life of refrigerated RTU and RTA nab-paclitaxel dispersions is limited to 7 days. Shelf life of RTA nab-paclitaxel dispersions stored at room temperature is limited to 4 days. Careful visual inspection of nab-paclitaxel dispersions after reconstitution and prior to administration is highly recommended to detect non-redispersible particles.

Hybrid Albumin-Decorated Lipid-Nanocarrier-Mediated Delivery of Polyphenol-Rich Sambucus nigra L. in a Potential Multiple Antitumoural Therapy.

The current research attempted to address the suitability of bioactive Sambucus nigra extract entrapped in albumin-decorated nanostructured lipid carriers (NLCs) as a promising "adjuvant" in improving tumour penetration for multiple antitumour therapy. The new hybrid albumin-decorated NLCs were characterised based on, e.g., the particle size, zeta electrokinetic potential, SambucusN entrapment efficiency, and fluorescence spectroscopy and tested for different formulation parameters. The antioxidant activity of NLC-SambucusN was significantly enhanced by a bovine serum albumin (BSA) polymer coating. According to the real-time cell analysis (RTCA) results, NLC-I-SambucusN-BSA behaved similarly to the chemotherapeutic drug, cisplatin, with cell viability for LoVo tumour cells of 21.81 ± 1.18%. The new albumin-NLC-SambucusN arrested cancer cells in G1 and G2 cycles and intensified the apoptosis process in both early and late phases. An advanced induction, over 50% apoptosis in LoVo colon cells, was registered for 50 μg/mL of NLC-II-SambucusN-BSA, a fourfold increase compared to that of untreated cells. RTCA and flow cytometry results showed that concentrations of the hybrid NLC-SambucusN up to 50 μg/mL do not affect the proliferation of normal HUVEC cells. This approach provides insightful information regarding the involvement of phytochemicals in future therapeutic strategies. Albumin-decorated NLCs can be considered a noteworthy strategy to be connected to antitumour therapeutic protocols.

Self-Assembled Micelles Based on Ginsenoside Rg5 for the Targeted Treatment of PTX-Resistant Tumors.

Paclitaxel (PTX) is one of the first-line drugs for prostate cancer (PC) treatment. However, the poor water solubility, inadequate specific targeting ability, multidrug resistance, and severe neurotoxicity are far from being fully resolved, despite diverse PTX formulations in the market, such as the gold-standard PTX albumin nanoparticle (Abraxane) and polymer micelles (Genexol-PM). Some studies attempting to solve the multiple problems of chemotherapy delivery fall into the trap of an extremely complicated formulation design and sacrifice druggability. To better address these issues, this study designed an efficient, toxicity-reduced paclitaxel-ginsenoside polymeric micelle (RPM). With the aid of the inherent amphiphilic molecular structure and pharmacological effects of ginsenoside Rg5, the prepared RPM enhances the water solubility and active targeting of PTX, inhibiting chemotherapy resistance in cancer cells. Moreover, the polymeric micelles demonstrated favorable anti-inflammatory and neuroprotective effects, providing ideas for the development of new clinical anti-PC preparations.

Magnetic ferrite nanoparticles coated with bovine serum albumin and glycine polymers for controlled release of curcumin as a model

To conquer the low water solubility and bioavailability of curcumin (CUR), to corroborate its functional qualities and to broaden its applicability in the pharmaceutical sector, numerous nanoscale methods have been widely exploited for its administration. Because of its polycystic, biodegradable, biocompatibility, non-toxicity, and non-allergenic properties, bovine serum albumin (BSA) and glycine (Gly) have been actively investigated as natural biopolymers for decades. Various BSA and Gly-based nanocarriers with unique features for CUR delivery, such as magnetic ferrite nanoparticles, are being developed (MNPs). In this work, magnesium ferrite (MgFe2O4)/BSA and nickel ferrite (NiFe2O4)/Gly nanocomposites loaded with CUR (drug model) were manufactured for the first time using a chemical co-precipitation approach to create biocompatible drug nanocarriers. It was found that the synthesized MgFe2O4/BSA and NiFe2O4/Gly nanoparticles have a uniform particle distribution and their size is much less than 100 nm. Saturation magnetization in MgFe2O4 and NiFe2O4 reaches 13.07 and 33.4 emu/g the remarkable peak of magnetization decreases to 10.99 and 32.36 emu/g after the addition of polymers. These analyses also showed the presence of chemical bonds in the structure of the nanocomposite. The curcumin diffusion process in NPs were determined using a mathematical modeling. The yielding of the product for MgFe2O4/BSA and NiFe2O4/Gly in 200 h is about 72 and 63%, respectively. Also, regressed relative diffusivities (D/R2), including effective steric hindrance, were determined as 5.75 × 10−4 and 2.72 × 10−4 h−1 for MgFe2O4/BSA and NiFe2O4/Gly, respectively. It shows that there is a significant steric barrier that significantly deviates from the molecular diffusion of the liquid. As a result, the low effective release of curcumin in the particles is more noticeable. Our study demonstrated the effective relationship between the polymer architecture and the biophysical properties of the resulting nanoparticles and shed light on new approaches for the design of efficient NP-based drug carriers.

Enhanced Ionic Polymer-Metal Composites with Nanocomposite Electrodes for Restoring Eyelid Movement of Patients with Ptosis.

The present study aims to use enhanced ionic polymer-metal composites (IPMC) as an artificial muscle (a soft-active actuator) to restore eyelid movement of patients with ptosis. The previous eyelid movement mechanisms contained drawbacks, specifically in the lower eyelid. We used finite element analysis (FEA) to find the optimal mechanism among two different models (A and B). In addition to common electrodes of IPMC (gold and platinum), the bovine serum albumin (BSA) and microcrystalline cellulose (MCC) polymers, with optimal weight percentages of carbon nanotube (CNT) nanofiller, were also utilized as non-metallic electrodes to improve the efficiency of the IPMC actuator. In both models, IPMC with nanocomposite electrodes had higher efficiency as compared to the metallic electrodes. In model A, which moved eyelids indirectly, IPMC with MCC-CNT electrode generated a higher force (25.4%) and less stress (5.9 times) as compared to IPMC with BSA-CNT electrode. However, the use of model A (even with IPMCs) with nanocomposite electrodes can have limitations such as possible malposition issues in the eyelids (especially lower). IPMC with MCC-CNT nanocomposite electrode under model B, which moved eyelids directly, was the most efficient option to restore eyelid movement. It led to higher displacements and lower mechanical stress damage as compared to the BSA-CNT. This finding may provide surgeons with valuable data to open a window in the treatment of patients with ptosis.

Attenuating ischemia-reperfusion injury with polymerized albumin.

Ischemia-reperfusion injury increased vascular permeability, resulting in fluid extravasation from the intravascular compartment into the tissue space. Fluid and small protein extravasation lead to increased interstitial fluid pressure and capillary collapse, impairing capillary exchange. Polymerized human serum albumin (PolyHSA) has an increased molecular weight (MW) compared with unpolymerized human serum albumin (HSA) and can improve intravascular fluid retention and recovery from ischemia-reperfusion injury. To test the hypothesis that polymerization of HSA can improve recovery from ischemia-reperfusion injury, we studied how exchange transfusion of 20% of the blood volume with HSA or PolyHSA immediately before reperfusion can affect local ischemic tissue microhemodynamics, vascular integrity, and tissue viability in a hamster dorsal window chamber model. Microvascular flow and functional capillary density were maintained in animals exchanged with PolyHSA compared with HSA. Likewise, exchange transfusion with PolyHSA preserved vascular permeability measured with extravasation of fluorescently labeled dextran. The intravascular retention time of the exchanged PolyHSA was significantly longer compared with the intravascular retention time of HSA. Lastly, the viability of tissue subjected to ischemia-reperfusion injury increased in animals exchanged with PolyHSA compared with HSA. Therefore maintenance of microvascular perfusion, improvement in vascular integrity, and reduction in tissue damage resulting from reperfusion with PolyHSA suggest that PolyHSA is a promising fluid therapy to improve outcomes of ischemia-reperfusion injury.NEW & NOTEWORTHY Polymerized human serum albumin reduced reperfusion injury and preservers microvascular hemodynamics. Polymerized human serum albumin reduces fluid extravasation and prevents fluid extravasation. Consequently, the tissue viability of ischemic tissue is preserved by polymerized human serum.

An Antibody-like Polymeric Nanoparticle Removes Intratumoral Galectin-1 to Enhance Antitumor T-Cell Responses in Cancer Immunotherapy.

Antibodies have shown potential to deplete immunosuppressive factors in tumor tissues. However, intrinsic drawbacks, including time-consuming processes in preparation, high cost, and short half-life time, greatly restrict their applications. In this work, we report an antibody-like polymeric nanoparticle (APN) that is capable of specifically capturing and removing galectin-1 in tumor tissues, thereby enhancing the antitumor T-cell responses. The APN is composed of an albumin-polymer hybrid nanoparticle (core) and an acid-responsive PEG shell. The core of the APN contains multiple recognition units and Tuftsin peptides to capture target factors and activate macrophage-mediated phagocytosis, respectively. By employing galactose as recognition units, the APN facilitated the phagocytosis of galectin-1 in tumor tissues, thereby improving the antitumor responses of tumor-infiltrating T cells. Since the recognition units in the APN can be further replaced to capture and remove other peptides/proteins, the APN provides a feasible approach for the development of synthetic nanoformulations to regulate biological systems and treat diseases.

Polymerized Albumin Receptor of Hepatitis B Virus for Evading the Reticuloendothelial System.

Various strategies, such as optimization of surface chemistry, size, shape, and charge, have been undertaken to develop nanoparticles (NPs) as DDS (drug delivery system) nanocarriers for evading the reticuloendothelial system (RES) in vivo. We previously developed a hollow NP composed of hepatitis B virus (HBV) surface antigen L proteins and lipid bilayers, hereinafter referred to as bio-nanocapsule (BNC), as a nonviral DDS nanocarrier. Such a BNC harbors the HBV-derived human hepatic cell-specific infection mechanism, and intravenously injected BNCs by themselves were shown to avoid clearance by RES-rich organs and accumulate in target tissues. In this study, since the surface modification with albumins is known to prolong the circulation time of nanomedicines, we examined whether the polymerized albumin receptor (PAR) of BNCs contributes to RES evasion in mouse liver. Our results show that NPs conjugated with peptides possessing sufficient PAR activity were captured by Kupffer cells less efficiently in vitro and were able to circulate for a longer period of time in vivo. Comparing with polyethylene glycol, PAR peptides were shown to reduce the recognition by RES to equal content. Taken together, our results strongly suggest that the PAR domain of BNCs, as well as HBV, harbors an innate RES evasion mechanism. Therefore, the surface modification with PAR peptides could be an alternative strategy for improving the pharmacodynamics and pharmacokinetics of forthcoming nanomedicines.

Tumor-Targeted Delivery of Bufalin-Loaded Modified Albumin-Polymer Hybrid for Enhanced Antitumor Therapy and Attenuated Hemolysis Toxicity and Cardiotoxicity.

A novel albumin polymer hybrid with a core-shell structure was designed to target delivery of bufalin, which is an antineoplastic monomer with serious cardiotoxicity. The sheath layer was composed of ursodeoxycholic acid (UA)-modified bovine serum albumin (UA-BSA), while the stable core consisted of poly n-butyl cyanoacrylate (PBCA) nanoparticles. The UA-BSA was synthetized, and the substitution degree was characterized. The physical properties of bufalin-loaded UA-modified protein-PBCA nanocomplexes (BF-uPPNCs), such as morphology, particle size, and encapsulation efficiency, were evaluated. FTIR and DSC revealed the bufalin to be in an amorphous state. Furthermore, the in vitro release study indicated a sustained release profile of BF-uPPNCs. The MTT and cellular uptake study demonstrated that BF-uPPNCs significantly improved the inhibitory effect of the bufalin accompanied with an enhanced cell uptake capacity on HepG2 cells. In addition, in vivo research demonstrated that BF-uPPNCs had a better antitumor effect coupled with improved therapeutic effect, and reduced hemolysis, vascular irritation, and cardiotoxicity. This work therefore presented a novel albumin polymer hybrid with favorable stability, efficient tumor-targeted delivery potential, and side effect reduction ability, which can be a potential vehicle for an anticancer drug.

Biocompatible SWCNT Conductive Composites for Biomedical Applications.

The efficiency of devices for biomedical applications, including tissue engineering and neuronal stimulation, heavily depends on their biocompatibility and performance level. Therefore, it is important to find adequate materials that meet the necessary requirements such as (i) being intrinsically compatible with biological systems, (ii) providing a sufficient electronic conductivity that promotes efficient signal transduction, (iii) having “soft” mechanical properties comparable to biological structures, and (iv) being degradable in physiological solution. We have developed organic conducting biocompatible single-walled carbon nanotubes (SWCNT) composites based on bovine serum albumin, carboxymethylcellulose, and acrylic polymer and investigated their properties, which are relevant for biomedical applications. This includes ζ-potential measurements, conductivity analyses, and SEM micrographs, the latter providing a local analysis of SWCNT distribution in the base material. We observed the development of the electrical conductivity of the SWCNT composites exposed to 1 mM KCl electrolyte for 40 days, representing a high stability of the samples. The conductivity of samples reaches 1300 S/m for 0.45 wt.% nanotubes. Moreover, we demonstrated the biocompatibility of the composites via cultivating fibroblast cell culture. Finally, we showed that composite coating results in the longer lifespan of cells on the surface. Overall, the SWCNT-based conductive composites might be a promising material for extended biomedical applications.

Formulation, Optimization, and Evaluation of Allopurinol-Loaded Bovine Serum Albumin Nanoparticles for Targeting Kidney in Management of Hyperuricemic Nephrolithiasis : Formulation, optimization, and evaluation of ABNPs for kidney targeting.

The aim of present research work was to design, fabricate, optimize, and evaluate allopurinol (ALLO)-loaded bovine serum albumin nanoparticles (ABNPs) for kidney targeting of the drug and exploring the potential of fabricated ABNPs for management of hyperuricemia-related nephrolithiasis. ABNP formulation was prepared by employing desolvation technique, and its optimization was conducted by 2-factor-3-level central composite design (CCD) in order to achieve minimum particle size (PSA) and polydispersity index (PDI), maximum entrapment efficiency (EE), and zeta potential (ZP). Further, the optimized formulation (ABNPsopt) was also assessed for in vitro drug release study, TEM, DSC, XRD analysis, FTIR spectroscopy, and in vivo animal study. The in vivo study revealed that after 2h of ABNPsopt administration, a significant concentration of ALLO was present in kidney (21.26-fold) as compared with serum while in case of standard pure drug group; no drug was seen in mice kidney and serum post 2h administration, which indicates successful targeting of ALLO by formulating its albumin nanoparticles. Also, uric acid and pH levels were measured in serum and urine samples of mice which showed significant (P < 0.01) efficacy of ABNPsopt formulation in management of hyperuricemia-related nephrolithiasis. Histological studies on kidney samples also confirmed these outcomes. Findings of present study indicate higher kidney uptake of allopurinol from formulated ABNPsopt, which could be due to the specificity of albumin polymer for cubilin and megalin receptors, and it also serves as effective strategy in management of hyperuricemic-related nephrolithiasis.

Mechanisms by Which Organic Solvent Exchange Transforms Responsive Pure Protein Hydrogels into Responsive Organogels.

Responsive pure protein organogel sensors and catalysts are fabricated by replacing the aqueous mobile phase of protein hydrogels with pure ethylene glycol (EG). Exchanging water for EG causes irreversible volume phase transitions (VPT) in bovine serum albumin (BSA) polymers; however, BSA hydrogel and organogel sensors show similar volume responses to protein-ligand binding. This work elucidates the mechanisms involved in this enabling irreversible VPT by examining the protein secondary structure, hydration, and protein polymer morphology. Organogel proteins retain their native activity because their secondary structure and hydration shell are relatively unperturbed by the EG exchange. Conversely, the decreasing solvent quality initiates polymer phase separation to minimize the BSA polymer surface area exposed to EG, thus decreasing distances between BSA polymer strands. These protein polymer morphology changes promote interprotein interactions between BSA polymer strands, which increase the effective polymer cross-link density and prevent organogel swelling as the mobile phase is exchanged back to water.

Peroxidase-Mimicking Nanoassembly Mitigates Lipopolysaccharide-Induced Endotoxemia and Cognitive Damage in the Brain by Impeding Inflammatory Signaling in Macrophages.

Oxidative stress during sepsis pathogenesis remains the most-important factor creating imbalance and dysregulation in immune-cell function, usually observed following initial infection. Hydrogen peroxide (H2O2), a potentially toxic reactive oxygen species (ROS), is excessively produced by pro-inflammatory immune cells during the initial phases of sepsis and plays a dominant role in regulating the pathways associated with systemic inflammatory immune activation. In the present study, we constructed a peroxide scavenger mannosylated polymeric albumin manganese dioxide (mSPAM) nanoassembly to catalyze the decomposition of H2O2 responsible for the hyper-activation of pro-inflammatory immune cells. In a detailed manner, we investigated the role of mSPAM nanoassembly in modulating the expression and secretion of pro-inflammatory markers elevated in bacterial lipopolysaccharide (LPS)-mediated endotoxemia during sepsis. Through a facile one-step solution-phase approach, hydrophilic bovine serum albumin reduced manganese dioxide (BM) nanoparticles were synthesized and subsequently self-assembled with cationic mannosylated disulfide cross-linked polyethylenimine (mSP) to formulate mSPAM nanoassembly. In particular, we observed that the highly stable mSPAM nanoassembly suppressed HIF1α expression by scavenging H2O2 in LPS-induced macrophage cells. Initial investigation revealed that a significant reduction of free radicals by the treatment of mSPAM nanoassembly has reduced the infiltration of neutrophils and other leukocytes in a local endotoxemia animal model. Furthermore, therapeutic studies in a systemic endotoxemia model demonstrated that mSPAM treatment reduced TNF-α and IL-6 inflammatory cytokines in serum, in turn circumventing organ damage done by the inflammatory macrophages. Interestingly, we also observed that the reduction of these inflammatory cytokines by mSPAM nanoassembly further prevented IBA-1 immuno-positive microglial cell activation in the brain and consequently improved the cognitive function of the animals. Altogether, the administration of mSPAM nanoassembly scavenged H2O2 and suppressed HIF1α expression in LPS-stimulated macrophages and thereby inhibited the progression of local and systemic inflammation as well as neuroinflammation in an LPS-induced endotoxemia model. This mSPAM nanoassembly system could serve as a potent anti-inflammatory agent, and we further anticipate its successful application in treating various inflammation-related diseases.

Affinity study on bovine serum albumin’s peptides to amphiphilic gold nanoparticles: A test of epitopes and non-epitopes

It is an inevitable event that nanoparticles (NPs) will encounter proteins/peptides in nano-medicine, so it has been significant to know their interaction mechanism before in vivo applications. Previously, a 105-amino-acid sequence had been reported as the binding site between bovine serum albumin (BSA) and amphiphilic polymer coated gold nanoparticles (AP-AuNPs) along with a mortise-tenon joint hypothesis. This article tested the affinity difference between two epitope peptide sequences such as: LGEYGFQNALIVR (S1), DAFLGSFLYEYSR (S2) and one non-epitope peptide sequence as: FDEHVKLVNELTEF (S3). With the photoluminescent amino acid residues, the fluorescence quenching method based on the nanometal surface energy transfer (NSET) principle was able to study the thermodynamics of the current binding system. The binding constants (Ka) were determined and followed the order as: Ka-S1>Ka-S2>>Ka-S3. Moreover, Hill constants indicated that cooperativity only presented in the interactions of AP-AuNP with either S1 or S2, but not for S3. Moreover, gel electrophoresis, surface plasmon resonance, atomic force microscopy and three dimensional fluorescence microscopy were all also used to comprehensively analyse the binding interaction mechanism. These results further provided useful information to better understand the mortise-tenon joint, which might find applications to nanofabrication and biomedicine.

Influencing Selectivity to Cancer Cells with Mixed Nanoparticles Prepared from Albumin–Polymer Conjugates and Block Copolymers

Albumin-based nanoparticles are widely used to delivery anticancer drug because they promote the accumulation of drugs in tumor sites. Nanoparticles with surface immobilized albumin are widely described in literature, although mixed nanoparticles with systematically modified ratios between albumin and PEG-based material are less common. In this work, hybrid nanoparticles were prepared by coassembly of a PEG-based amphiphilic block copolymer together with a polymer-protein conjugate. Poly(oligo(ethylene glycol) methyl ether acrylate)-poly(ε-caprolactone) (POEGMEA-PCL) was prepared by a combination of ring-opening polymerization and reversible addition-fragmentation chain transfer (RAFT) polymerization, while the polymer-protein conjugate was obtained by reacting poly(ε-caprolactone) with bovine serum albumin (BSA-PCL). Co-assembly of both amphiphiles at different ratios, with and without curcumin as a drug, led to hybrid nanoparticles with various amount of albumin on the particle surface. The resulting hybrid nanoparticles were similar in size (100-120 nm), but increasing the amount of albumin on the surface led to a more-negative ζ potential. The cytotoxicity of the curcumin-loaded nanoparticles was examined on several cell lines. The curcumin-loaded nanoparticles with high amount of albumin led to high cytotoxicity against breast cancer cell lines (MDA-MB-231 and MCF-7), which coincided with high cellular uptake. However, the cytotoxicity of the curcumin-loaded nanoparticles against CHO cells and RAW264.7 cells was reduced, suggesting that albumin can facilitate selectivity toward cancer cells.

Astaxanthin conjugated polypyrrole nanoparticles as a multimodal agent for photo-based therapy and imaging

Polymeric nanoparticles are emerging as promising candidates for photo-based therapy and imaging due to their versatile chemical properties and easy fabrication and functionalization. In the present study we synthesized polypyrrole nanoparticles by stabilization with astaxanthin conjugated bovine serum albumin polymer (PPy@BSA-Astx). The synthesized nanoparticles were biocompatible with MBA-MD-231 and HEK-293 cells. Interestingly, the fabricated nanoparticles produced reactive oxygen species under 808-nm laser exposure and exerted a hyperthermic effect when the power density of the laser was increased. The photodynamic efficiency of PPy@BSA-Astx was measured by DPBF assay, and it was found to generate sufficient amount of reactive radicals to kill the cells at a power density of 0.3W/cm2. In photothermal aspect, the temperature level was reached to 57°C within 5min at 1W/cm2 power density, at the concentration of 50μg/mL. The in vitro cell toxicity studies showed concentration dependent photothermal and photodynamic toxicity. Fluorescence microscopic investigation explored the cell death and intra-cellular organ destruction by photodynamic treatment. In addition, we observed a strong photoacoustic signal from a tissue mimicking phantom study of nanoparticle treated MBA-MD-231 cells. In conclusion, the fabricated PPy@BSA-Astx nanoparticles can be used as photoacoustic imaging based prognostic agents for photothermal or photodynamic treatment.

Preparation and Self-Assembly Mechanism of Bovine Serum Albumin-Citrus Peel Pectin Conjugated Hydrogel: A Potential Delivery System for Vitamin C.

In this study, a novel hydrogel (BSA-pectin hydrogel, BPH) was prepared via a self-assembly method by using the natural polymers of bovine serum albumin (BSA) and citrus peel pectin (pectin). The rheological properties and gel conformational structures were determined and showed that electrostatic and covalent interactions between BSA and pectin were the main mechanisms for the formation of BPH. The morphological characteristics of BPH included a stable and solid three-dimensional network structure with a narrow size distribution (polydispersity index <0.06). BPH was used as a delivery system to load the functional agent vitamin C (Vc). The encapsulation efficiency (EE) and release properties of Vc from BPH were also investigated. The results revealed that the EE of Vc into BPH was approximately 65.31%, and the in vitro Vc release from BPH was governed by two distinct stages (i.e., burst release and sustained release) in different pH solutions, with release mechanisms involving diffusion, swelling, and erosion. Meanwhile, the stability results showed that BPH was a stable system with an enhanced Vc retention (73.95%) after 10 weeks of storage. Thus, this three-dimensional network system of BPH may be a potential delivery system to improve the stability and bioavailability of functional agents in both food and non-food fields.

Understanding the Robust Physisorption between Bovine Serum Albumin and Amphiphilic Polymer Coated Nanoparticles.

The robust physisorption between nanoparticles (NPs) and proteins has attracted increasing attention due to the significance for both conjugation techniques and protein's corona formation at the bionano interface. In the present study, we first explored the possible binding sites of the bovine serum albumin (BSA) on amphiphilic polymer coated gold nanoparticles (AP-AuNPs). By using mass spectrometry, a 105-amino-acid peptide (12.2 kDa) is discovered as the possible "epitope" responsible for the robust physisorption between BSA and AP-AuNPs. Second, with the help of nanometal surface energy transfer (NSET) theory, we further found that the epitope peptide could insert at least 2.9 nm into the organic molecular layers of AP-AuNPs when the robust conjugates formed, which indicates how such a long epitope peptide can be accommodated by AP-AuNPs and resist protease's digestion. These findings might shed light on a new strategy for studying interactions between proteins and NPs, and further guide the rational design of NPs for safe and effective biomedical applications.

Albumin-polymer conjugate nanoparticles and their interactions with prostate cancer cells in 2D and 3D culture: comparison between PMMA and PCL.

Using proteins as the hydrophilic moiety can dramatically improve the biodegradability and biocompatibility of self-assembled amphiphilic nanoparticles in the field of nanomedicine. In this study, we fabricated and evaluated curcumin loaded albumin-polycaprolactone nanoparticles as a novel drug delivery system for prostate carcinoma therapeutics and compared their performance to poly(methyl methacrylate) (PMMA), a non-degradable and amorphous polymer. The maleimide functionalized poly(ε-caprolactone) (PCL) was obtain using ring opening polymerization (ROP) of ε-caprolactone where N-(2-hydroxyethyl)maleimide was used as an initiator. The resorbable albumin-polymer conjugate was prepared by conjugating the hydrophobic maleimide-terminated PCL to the hydrophilic bovine serum albumin (BSA) via a simple Michael addition reaction. PMMA was conjugated in a similar manner. The amphiphilic BSA-polymer conjugates can self-assemble into nanoparticles, displaying well-defined structure, prolonged storage stability, and excellent biocompatibility. The BSA nanoparticles, with encapsulated curcumin, exhibited highly enhanced antitumor activity compared to free curcumin. Furthermore, the high efficacy of the curcumin loaded nanoparticles was verified by effectively inhibiting the growth of three-dimensional LNCaP multicellular tumour spheroids. The cytotoxicity was attributed to the efficient cellular uptake of the nanoparticles through caveolic endocytosis. The direct comparison between PCL and the PMMA revealed that drug loading and release as well as cytotoxicity is not significantly affected by the nature of the polymer. However, it seems that nanoparticles based on PMMA penetrate quicker into LNCaP multicellular tumour spheroids thanks to the increased stability. The faster penetration was found to reduce the toxicity of the nanoparticles as evidenced by the lower number of dead cells. In contrast, the fully degradable PCL-based nanoparticles were more efficient in delivering the drug, thus limiting the growth of LNCaP multicellular tumour spheroids.

Evaluation of anti-metastatic potential of Cisplatin polymeric nanocarriers on B16F10 melanoma cells

Nanoparticles are being increasingly used in the field of cancer treatment due to their unique properties and advantages. The aim of the present research work was to prepare and characterize a polymeric albumin nanosystem for Cisplatin and evaluate its in-vitro efficacy against B16F10 melanoma. The developed nanoparticles were almost spherical in shape with a particle size in the range of 150–300nm, low polydispersity values and about 80% drug entrapment efficiency. Albumin nanocarriers sustained the release of Cisplatin for more than 48h, suggesting the reduction in dosing schedule for this drug. The results from in-vitro cell line studies indicated the dose dependent cytotoxic potential of drug loaded albumin nanoparticles, their potential to inhibit cell proliferation and induce morphological changes. In addition, these nanoparticles exhibited superiority to Cisplatin in hampering the cell migration. Developed nanoparticles caused cell cycle arrest along with time and concentration dependent cellular uptake in B16F10 cell line. These results signify that the prepared Cisplatin albumin nanoparticles could serve as a promising approach for B16F10 melanoma treatment.