The purpose of this study is to evaluate the influence of phospholipid-polymer nanoparticles (PNPs) on mitogenactivated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling of dopaminergic neurons in degenerated brain. Resveratrol (RES)- and ceftriaxone (CEF)-entrapped PNPs with surface leptin (Lep) and transferrin (Tf) were fabricated to rescue both 1-methyl-4-phenylpyridinium (MPP+)-insulted SH-SY5Y cells and Wistar rats. Based on PNPs, anti-apoptosis of RES and CEF, and targeting of Lep and Tf were investigated. Experimental results revealed that 20-30 % alginic acid (Alg) yielded the maximal particle size, physical stability and entrapment efficiency of CEF, and the minimal release percentage of CEF. Increasing Alg content in PNPs decreased the entrapment efficiency of RES, and facilitated the release of RES. Optimized PNP composition was about 40 % Alg, 15 % phosphatidylserine and 45 % poly-epsilon-caprolactone. Lep-Tf-PNPs ameliorated brain permeability of RES and CEF without jeopardizing the blood-brain barrier, and promoted the viability of MPP+insulted SH-SY5Y cells. Immunofluorescence images and western blots of MPP+-insulted SH-SY5Y cells showed that Lep-Tf-RES-CEF-PNPs upregulated dopamine transporter, tyrosine hydroxylase, B-cell lymphoma 2 (Bcl-2), cyclic AMP response element-binding protein and ERK5 expressions, and downregulated Bcl-2-associated X protein (Bax), alpha-synuclein (alpha-syn), phosphorylated tau protein (p-tau), c-Jun N-terminal kinase and ERK1/2 expressions. Lep-Tf-RES-CEF-PNPs unveiled a strong capacity to recover Bcl-2, Bax, alpha-syn and p-tau levels from MPP+ injury in the substantia nigra of rats. Hence, Lep-Tf-RES-CEF-PNPs can retard alpha-syn fibril formation, prevent tau protein from phosphorylation, and moderate MAPK/ERK and phosphatidylinositol 3-kinase/protein kinase B, and are promising for brain- and neuron-targeted pharmacotherapy to manage Parkinson's disease.

Encapsulated BV6 and SM164, two bivalent second mitochondria-derived activator of caspase (Smac) mimetics, in etoposide (ETO)-lipopolymer nanoparticles (NPs) have been developed to deplete inhibitor of apoptosis proteins (IAP), impair DNA, and produce antagonistic effects on glioblastoma multiforme (GBM) in nude mice. The NPs, composed of cocoa butter (CB) and polyvinyl alcohol (PVA), were stabilized by glycerol monostearate and Pluronic F-127, and grafted with transferrin (Tf) and wheat germ agglutinin (WGA) to dock the blood-brain barrier (BBB) and degenerated dopaminergic neurons. The dual-targeting NPs increased the BBB permeability of BV6, SM164 and ETO via recognizing Tf receptor (TfR) and N-acetylglucosamine that are abundantly expressed on brain microvascular endothelial cells. The sustained release of BV6, SM164 and ETO from CB-PVA-NPs for 48 h resulted in a reduction of about 40 % in the viability of U87MG cells and human brain cancer stem cells. Hematoxylin and eosin staining of the brain in GBM mice revealed atypical mitosis of cancer cells and a considerable decrease in tumor cell density after treatment with Tf-WGA-BV6-SM164-ETO-NPs. Compared to untreated mice, the current ETO preparation carrying Smac mimetics reduced cellular IAP-1 expression to about 33 % and X-linked IAP expression to about 42 %, while enhanced about 3.8-fold caspase-3, indicating the effectiveness of the nanocarriers in accelerating apoptosis of GBM cells. Tf-WGA-CB-PVA-NPs can be promising to upgrade BV6 and SM164 activity by ETO in clinical trials for GBM management.

Background Glioblastoma multiforme (GBM), the most prevalent and deadly tumor in the central nervous system, posed a formidable challenge to healthcare. The prognosis revealed a varied and aggressive characters of malignancy to exacerbate GBM illness with comorbidities like diabetes mellitus (DM) for standard therapy. In addition, the differentiation of cancer stem cells and the blood-brain barrier (BBB) incited the major weakness of radiation and chemotherapy for GBM. Methods With the understanding that DM promoted GBM pathogenesis through mechanisms, such as inflammatory and immune responses, our research aimed to address this complex interplay through innovative nanotechnology. Leveraging the unique properties of biomaterials, including the ability to penetrate the BBB and to selectively conjugate tumor cells, we hypothesized that nanotherapeutics could construct a promising avenue for intervention of GBM with DM. Significant findings Nanomaterial-mediated release of chemotherapeutics surpassed the limitations of conventional preparation for GBM treatment, improved pharmacokinetics, and reduced systemic toxicity with better safety in GBM patients with DM. The strategy to retard GBM propagation focused on targeted delivery of pharmacotherapeutic agents across the BBB with nanoparticles, peptides and monoclonal antibodies. Moreover, type 2 diabetes mellitus (T2DM) was treated with a variety of modalities. T2DM patients must receive strict antidiabetic medication when diet and exercise failed to control hyperglycemia. The main drawbacks of T2DM treatment were fast release and inadequate absorption of the medicine via oral administration, and an increase in the frequency of dose was required. Epidemiologic evidence indicated that GBM was associated with T2DM and with diabetes risk factors. Consensus of biomedical experts suggested the connection of GBM incidence to T2DM, including common pathologic factors in T2DM and GBM, influence of diabetes treatment on GBM risk, and possible biologic links between T2DM and GBM. To enhance bioactivity, biosafety and solubility, prolong release, and boost BBB permeability, biomaterial drug delivery system attracted strong attentions. Through investigating a series of in vitro and in vivo models, this study featured the panorama of recently developed nanocarriers to mitigate GBM evolution in diabetic population with minimized systemic side effects. We also evaluated the up-to-date studies, and emphasized the remained problems related to nano-preparation in clinical trials for GBM therapy.

It is one of the challenging works to deal with second major cause of death due to cancer and to reduce the mortality rate caused by this. Researchers have been finding various approaches to minimise the unwanted effect of cancer therapy and increase the selectivity of the cancer cells that are cancerous without harming the normal cells. Accordingly, they have discovered and reported a series of anti-cancer complexes with moderate to high selective behaviour. Conventional cancer therapies are resistant to some of standard drugs. When we consider the group of metallotherapeutic anticancer agents, platinum (Pt) based anti-neoplastic complexes have some drawbacks and lower potency and selectivity than complexes like Ruthenium (Ru), Iridium (Ir), Rhodium (Rh) and Rhenium (Re) towards various cancer cell lines (in vitro). Many of them have proved the in vivo applications. This review aims to provide a comprehensive summary of prior literature pertaining to the cytotoxic impact and cellular uptake of those metallocomplexes (Ru, Ir, Rh and Re), with particular emphasis on recently developed metal-based complexes. Most of them target the DNA, mitochondria, and induces cancer cell apoptosis lowering the adverse drug reaction.

Background: The connection between type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD) was first pointed out in the early 1960s. This probable link is still under serious consideration nowadays. Methods: Neurological changes caused by T2DM could be relevant to PD that included neuroinflammation, dopaminergic deregulation, reduction in the expression of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha, increment in the expression of phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes 15 and acceleration of alpha-synuclein (alpha-Syn) amyloid fibril formation. Furthermore, medical evidence disclosed that significantly exacerbated PD symptoms were associated with the initiation of T2DM, and common genes were concurrently found in DNA of T2DM and PD patients. Insulin resistance and microbiota dysbiosis of the gut-brain axis also connected DM to PD, explaining DM could be a risk factor for PD. In terms of treatment, antidiabetic drugs appeared to engender a certain degree of neuroprotective activity against PD. During drug delivery to the central nervous system, biomaterials could play a crucial role in permeating the blood-brain barrier (BBB) and recognizing exact cerebral tissue to rescue neurons from degeneration. Exosomes, liposomes, micelles, solid lipid nanoparticles, dendrimers, niosomes and nano-sized polymers have been developed to enhance drug and gene efficacy in brain targeting for PD management. In order to boost BBB permeability and alpha-Syn conjugation, the surface of these nanocarriers (NCs) were modified with active biomolecules, for instance, lactoferrin, angiopep and OX26. Natural exosomes were exposed to a limited number, and can be an efficient vector in analyzing the pathways from DM toward PD for clinical trials. Significant findings: This review focuses on understanding the pathophysiological relation between T2DM and PD, and the treatment for the two diseases with NCs. We also highlight the problems that have been solved and the challenges that continue.

Regeneration of insulin-producing cells (IPCs) from induced pluripotent stem cells (iPSCs) under controlled conditions has a lot of promise to emulate the pancreatic mechanism in vivo as a foundation of cell-based diabetic therapy. l-Glutamic acid-gelatin scaffolds with orderly pore sizes of 160 and 200 μm were grafted with activin A and bone morphogenic proteins 4 (BMP4) to differentiate iPSCs into definitive endoderm (DE) cells, which were then guided with fibroblast growth factor 7 (FGF7)-grafted retinoic acid (RA)-loaded solid lipid nanoparticles (FR-SLNs) to harvest IPCs. Response surface methodology was adopted to optimize the l-glutamic acid-to-gelatin ratio of scaffolds and to optimize surfactant concentration and lipid proportion in FR-SLNs. Experimental results of immunofluorescence, flow cytometry, and western blots revealed that activin A (100 ng/mL)-BMP4 (50 ng/mL)-l-glutamic acid (5%)-gelatin (95%) scaffolds provoked the largest number of SOX17-positive DE cells from iPSCs. Treatment with FGF7 (50 ng/mL)-RA (600 ng/mL)-SLNs elicited the highest number of PDX1-positive β-cells from differentiated DE cells. To imitate the natural pancreas, the scaffolds with controlled topography were appropriate for IPC production with sufficient insulin secretion. Hence, the current scheme using FR-SLNs and activin A-BMP4-l-glutamic acid-gelatin scaffolds in the two-stage differentiation of iPSCs can be promising for replacing impaired β-cells in diabetic management.

Inhibition to glioblastoma multiforme (GBM) propagation is a critical challenge in clinical practice because binding of inhibitors of apoptosis proteins (IAPs) to caspase prevents cancer cells from death. In this study, folic acid (FA), lactoferrin (Lf) and rabies virus glycoprotein (RVG) were grafted on lipopolymers (LPs) composed of poly(ε-caprolactone) and Compritol 888 ATO to encapsulate AZD5582 (AZD), GDC0152 (GDC) and curcumin (CURC). The standard deviations of initial particle diameter and particle diameter after storage for 30 days were involved in LP composition optimization. The functionalized LPs were used to permeate the blood-brain barrier (BBB) and constrain IAP quantity in GBM cells. Experimental results revealed that an increase in Span 20 (emulsifier) concentration enlarged the size of LPs, and enhanced the entrapment and releasing efficiency of AZD, DGC and CURC. 1H nuclear magnetic resonance spectra showed that the hydrogen bonds between the LPs and drugs supported the sustained release of AZD, DGC and CURC from the LPs. The LPs modified with the three targeting biomolecules facilitated the penetration of AZD, GDC and CURC across the BBB, and could recognize U87MG cells and human brain cancer stem cells. Immunofluorescence staining, flow cytometry and western blot demonstrated that CURC-incorporated LPs enhanced AZD and GDC activity in suppressing cellular IAP 1 (cIAP1) and X-linked IAP (XIAP) levels, and raising caspase-3 level in GBM. Surface FA, Lf and RVG also promoted the ability of the drug-loaded LPs to avoid carcinoma growth. The current FA-, Lf- and RVG-crosslinked LPs carrying AZD, DGC and CURC can be promising in hindering IAP expressions for GBM management.

•We deliberate basic concept, design, photostability, brain permeation and targeting of carbon dots (CDs).•CDs ameliorate misfolded α-amyloid peptide, entangled tau protein and aggregated α-synuclein.•CDs promote cognitive and mobile function in neurodegenerative disease treatment.•CDs can disclose pathological linkage between Alzheimer's disease (AD) and Parkinson's disease (PD).•Targeting pathogenic pathways behind AD and PD with CDs can be important.

Background: Smac mimetics functioned against inhibitors of apoptosis proteins (IAP) often fail to achieve sufficient ability in glioblastoma multiforme (GBM) treatment due to the obstruction of the blood-brain barrier (BBB). Methods: BV6-and GDC0152-encapsulated solid lipid nanoparticles (SLNs) with surface transferrin (Tf) and folic acid (FA) (BV6-GDC0152-Tf-FA-SLNs) were developed to downregulate IAP in U87MG cells and human brain cancer stem cells (HBCSCs) for GBM treatment. Significant findings: An increase in stearic acid (SA) level enlarged SLNs with improved entrapment of BV6 and GDC0152. H-1 NMR study revealed hydrogen bonding between SA and the two IAP antagonists, supporting controlled release of BV6 and GDC0152 from SLNs. Increasing sodium dodecyl sulfate concentration reduced the size of SLNs, and raised the particle stability. Conjugated Tf and FA on SLNs favored permeating the BBB as corroborated from decreased transendothelial electrical resistance, and raised BBB permeability of propidium iodide, BV6 and GDC0152. The ability of BV6-GDC0152-Tf-FA-SLNs to target IAP in U87MG cells and HBCSCs was validated from the downregulated XIAP and cIAP-1 expressions and upregulated caspase-3 expression in immunofluorescence staining, flow cytometry and western blot analysis. Hence, Tf-and FA-grafted SLNs can be an effective colloidal delivery system to deliver BV6 and GDC0152 across the BBB, facilitate IAP targeting, and enhanced drug bioavailability of the two Smac mimetics in GBM cells for potential clinical trials.

Purpose In recent years, tissue engineering scaffolds have gained popularity as a replacement for metallic/synthetic implants and tissue grafts. Methods A porous tricomponent scaffold of graphene oxide (GO)-xanthan-hydroxyapatite (HAP) was fabricated using the freeze-drying process for bone tissue engineering. Results The physicochemical analysis (FTIR and XRD) revealed that the composite was formed by hydrogen bonding and electrostatic interactions, and also determined a decreased crystallinity, similar to that of real bone apatite. TG/DTA analysis proved the presence of all the raw materials in the scaffold. Morphological studies supported the porous nature of HAP as well as its uniform distribution. The scaffold negatively charged functional group produced positive in vitro results in terms of cell proliferation, biocompatibility, and cell adhesion. Conclusion The positive in vitro results confirmed that the fabricated scaffold materials could be a useful biomaterial for bone tissue engineering.

Background: Tumor malignancy is one of the most atrocious threats to human survival. Although a vast range of remedies against neoplasms has been established over the course of several decades, there are still no systematic options to assure an absolute cure. The lack of full treatment for malignant tumors is partly attributed to no potent breakthrough in abating multidrug resistance and in augmenting chemotherapeutic targeting and biocompatibility. Even more importantly, inhibitor of apoptosis protein (IAP) overexpression can block apoptotic pathways via suppressing caspases, and further result in faster carcinomatous metastasis and transformation, making the medication difficult. Methods: To manage tumor progression, strategies related to drugs and genes which restrain IAPs are gaining traction by medicinal researchers and practitioners as an innovative methodology. Nonetheless, using small molecular entities, such as second mitochondria-derived activator of caspase mimetics, plasmid deoxyribonucleic acid and small interfering ribonucleic acid, to constrain IAP expression reveals many drawbacks, including insufficient selectivity and low bioavailability. Thus, drug-gene delivery materials become crucial to assist IAP antagonists for targeting carcinomatous tissue with accelerated cancer cell and cancer stem cell apoptosis. Significant Findings: We select the leading scientific findings about polymeric nanoparticles and liposomes, and highlight their functions and perspectives on transferring pharmaceuticals to cellular IAPs, X-linked IAP and survivin. In addition to the latest advancement, this review discusses the key problems that have been solved by IAP antagonist-loaded biomaterials and the questions that remain. These recently published literatures demonstrate that the developed materials can certainly activate caspase activity, and have high feasibility to retard tumor propagation for clinical trials in the near future. (c) 2022 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.

Upregulated proliferation of neoplastic cells from suppressing apoptotic signals associated with the inhibitors of apoptosis proteins (IAP) makes difficult the achievement of therapeutic efficiency against glioblastoma multiforme. Studies in the last few years have witnessed a paradigm focusing on targeting IAP using its antagonists, such as Smac mimetics, to restrain tumor malignancy. A Smac mimetic compound needs to penetrate the blood-brain barrier (BBB), and must be internalized into cerebral tumor for improved chemotherapy. Rabies virus glycoprotein (RVG) and lactoferrin (Lf)-grafted liposomes were developed in this study to carry two IAP antagonists, AZD5582 and SM-164, across the BBB and to induce apoptosis in U87 MG and human brain cancer stem cells (HBCSCs). Liposomes modified with RVG slightly reduced BBB tightness and enhanced capability of AZD5582 and SM-164 for traversing the barrier because of their brain-targeting ability. Immunofluorescence and western-blot results revealed that AZD5582- and SM-164-encapsulated liposomes facilitated mutual curative intensity, effectively triggered apoptosis of U87 MG and HBCSCs, reduced the expression of cellular IAP 1 (cIAP1) and X-linked IAP (XIAP), and enhanced the expression of caspase-3. Hence, RGV-Lf-liposomes carrying AZD5582 and SM-164 can be promising formulations to activate apoptosis of U87 MG and HBCSCs, and this functionalized drug delivery system targeting cIAP and XIAP is a potential strategy to cure glioblastoma in clinical cancer management.

Background: From ongoing human clinical trials, cell therapy for diabetic treatment using islet-like organoid generation from induced pluripotent stem cells (iPSCs) appears to have a promising future. Methods: Development of islet cells from iPSCs was guided in activin A- and Wnt3a-grafted gelatin-polyacrylamide inverted colloidal crystal scaffolds (activin A-Wnt3a-Gel-PAAM ICCS) with pore sizes of 70 and 160 mu m, followed by regulation with fibroblast growth factor 7-grafted retinoic acid-entrapped solid lipid nanoparticles (FGF7-RA-SLNs). Significant Findings: FGF7-RA-SLNs diffused into activin A-Wnt3a-Gel-PAAM ICCS, and controlled differentiation of definitive endoderm (DE) cells into islet cells. The immunochemical staining, flow cytometry and western blot demonstrated combined effects among activin A and Wnt3a, FGF7 and RA in materials for the 2-step differentiation. Wnt3a on the pore surface promoted activin A activity for generating DE cells, and FGF7 enhanced RA activity for producing islet cells. Under glucose stimulation, activin A-Wnt3a-Gel-PAAM ICCS with pore sizes of 70 mu m were prone to regenerate insulin-producing beta-cells rather than alpha cells. The optimized conditions for insulin secretion from beta-like cells in this study were pore size of 70 mu m, Gel:PAAM of 7:3, 100 ng/mL activin A, 100 ng/mL Wnt3a, 50 ng/mL FGF7 and 600 ng/mL RA. Activin A-Wnt3a-Gel-PAAM ICCS associated with FGF7-RA-SLNs can be effective in forming biomimetic pancreas and supporting cell therapy from iPSCs for diabetic management.

The unique structural characteristics and superior biocompatibility make the protein nanofibers promising immobilization platforms/substrates for catalysts/enzymes. Metal nanoparticles have been employed as the catalysts in industries due to their excellent catalytic activity and stability, whereas their high surface energy leads to nanoparticle aggregation, thereby hampering their catalytic performance. Here, amyloid fibril (AF) derived from whey protein isolate (WPI) was chosen as the support of silver nanoparticles (AgNP) and utilized for the catalytic reduction of methylene blue (MB). The one-dimensional amyloid-based hybrid materials (AgNP/WPI-AF) were first synthesized via chemical or photochemical route. The characterization of AgNP/WPI-AF by UV-vis spectrophotometry and electron microscopy revealed that the sizes of AgNP on WPI-AF's surface ranged from 2 to 30 nm. Next, the catalytic performances of AgNP/WPI-AF prepared by various routes for MB degradation were investigated. Additionally, the kinetic data were analyzed using two different models and the apparent rate constants and thermodynamic parameters were further determined accordingly. Moreover, the reusability of AgNP/WPI-AF was assessed by monitoring the percentage removal of MB over consecutive filtering cycles. Our results indicated that Langmuir-Hinshelwood-type mechanism better described the catalytic MB reduction using AgNP/WPI-AF. This work provides a nice example of application of nanoparticle-amyloid fibril composite materials for catalysis.

In recent years, Ru(II) complexes have gained high importance in medicinal chemistry due to their significant anti-cancer activities, which are directly related to their DNA binding ability. In this report, the chemistry and cytotoxicity of two new Ru(II) complexes containing imidazole pyridine (Ru-1) and imidazole quinoline (Ru-2) have been studied. The prepared compounds were characterized using infrared (IR), nuclear magnetic resonance (NMR), mass spectrometry (MS), isothermal titration calorimetry (ITC), UV-Vis, and fluorescence spectral techniques. The structural analyses show that the Ru(II) complexes exhibit a 'piano stool' coordination geometry and they are composed of one bound arene, two sigma bonded benzil nitrogen atoms, and labile chlorine linked to Ru(II). The photo-physical properties of these complexes were examined, and they exhibit absorption peaks at 260 nm and 380 nm, which are due to the involvement of intra-ligand charge transitions (ILCT) and metal-to-ligand charge transitions (MLCT), respectively. The binding process of the Ru(II) complexes with DNA and BSA is non-covalent in nature and the binding constants of Ru-1 and Ru-2 complexes with DNA and BSA were found to be 1 × 105 M-1 and 1 × 103 M-1, respectively. In the presence of the Ru(II) complexes, ethidium bromide (EtBr) is competitively displaced from DNA by intercalation of the Ru(II) complexes in DNA and it is well corroborated by viscosity and in silico studies. Both the ligands and Ru(II) complexes were carefully investigated in vitro for cytotoxicity against HeLa, MCF-7, and MDA-MB-231 cells. Surprisingly, both Ru(II) complexes exhibit superior cytotoxicity to cisplatin with a low LD50 value against the examined cancer cells. Besides, an insignificant effect on HEK normal cells (LD50 > 140 μM) was observed.

Background: The difficulty of drugs to cross the blood-brain barrier (BBB) to reach specific sites and target multiple factors responsible for neurovegetative diseases necessitates the development of an effective drug delivery system. Methods: Rabies virus glycoprotein (RVG)-and transferrin (Tf)-grafted liposomes were constructed to deliver epigallocatechin gallate (EGCG) and FK506 to BBB against neurodegeneration for Parkinson's disease (PD) treatment. Significant findings: Surface RVG and Tf revealed substantial improvement in BBB permeability of EGCG and FK506, and incorporation of phosphatidy-l-serine (PS) in RVG-Tf-EGCG-FK506-liposomes ameliorated a-syn-uclein docking. EGCG and FK506-encapsulated liposomes decreased cytotoxicity to 1-methyl-4-phenylpyridinium-impacted neurons. Immunofluorescence and western blot studies demonstrated better activity of RVG-Tf-EGCG-FK506-PS-liposomes in suppressing Bax, alpha-synuclein, caspase-3, p-tau protein, p-p38, pERK1/2 and p-cJNK expressions, and in increasing Bcl-2, tyrosine hydroxylase, dopamine transporter, p-CREB and p-ERK5 expressions. Multi-targeted RVG-Tf-PS-liposomes advantaged BBB permeation and contributed to neuroprotective effect to promote the efficiency of EGCG and FK506 in PD management. (c) 2021 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.

Complex liposomes were assembled with 1,2-distearoyl-sn-glycero-3-phosphocholine, dihexadecyl phosphate (DHDP), cholesterol and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphate (PA) to act as drug carriers for resveratrol (RES) and epigallocatechin gallate (EGCG). The liposomes were modified with leptin (Lep) on the surface to cross the blood-brain barrier (BBB) and to rescue degenerated dopaminergic neurons. The activity of RES and EGCG against neurotoxicity was investigated using an in vitro neurodegenerative model established by SH-SY5Y cells with an insult of 1-methyl-4-phenylpyridinium (MPP+). The results indicated that increasing the mole percentage of DHDP and PA increased the particle size and absolute zeta potential value, and improved the entrapment efficiency of RES and EGCG; however, this increase reduced the release rate of RES and EGCG and the grafting efficiency of Lep. The ability of Lep/RES-EGCG-PA-liposomes to cross the BBB was found to be higher than that of non-modified liposomes. Further, the addition of PA and Lep into liposomes enhanced cell viability and target efficiency. The immunofluorescence results demonstrated that the conjugation of Lep with liposomes enabled the docking of HBMECs and SH-SY5Y cells via Lep receptor, and enhanced their ability to permeate the BBB and cellular uptake. Immunofluorescence and western blot analysis also revealed that RES and EGCG encapsulated into liposomes could be a neural defensive strategy by reducing the apoptosis promotor protein Bcl-2 associated X protein and α-synuclein, and enhancement in the apoptosis inhibitor protein B cell lymphoma 2, tyrosine hydroxylase, and the dopamine transporter. Hence, Lep-PA-liposomes can be an excellent choice of potential delivery system for PD treatment.

Background: Scaffolds containing two kinds of regular pore size that support differentiation and proliferation of induced pluripotent stem cells (iPSC) are important approaches to artificial pancreas. Methods: This study aimed to differentiate iPSC in dual-sized gelatin (Gel)-alginate (Alg)-hyaluronic acid (HA) scaffolds containing inverted colloidal crystal (ICC) topography with 70-mm and 160-mm pore sizes for insulin production. The pore surface of dual-sized Gel-Alg-HA ICC scaffolds was grafted with growth differentiation factor 8 (GDF-8) and Wnt3a, and treated with retinoic acid (RA) and noggin to improve the differentiation of iPSC toward endodermic cells, and then islet cells. Findings: An increasing weight percentage of Gel increased the adhesion efficiency of iPSC. Moreover, Alg and HA helped to promote the proliferation and survival rate of iPSC, which resulted in a higher availability of iPSC for differentiation into insulin-production cells. Immunofluorescence staining, flow cytometry and western blot evidenced that dual-sized Gel-Alg-HA ICC scaffolds grafted with GDF-8 and Wnt3a enhanced the differentiation of iPSC into endodermic cells. When subsequent treatment with RA and noggin, endodermic cells differentiation into insulin-production cells in the scaffolds were improved. Precisely controlling the physical and biomedical properties of dual-sized Gel-Alg-HA ICC scaffolds can guide iPSC to differentiate first into endodermic cells, and then into pancreatic P-cells for diabetic treatment. (c) 2021 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.