Polylactic Acid-polyethylene Glycol Research Articles

Long‐acting release of small molecules achieved by barrier effect of nano‐brick

AbstractThe long‐acting sustained‐release of active molecules is of great importance in chemical production, food preservative, drug delivery in vivo, and so on. However, the problems of initial‐burst release and short release time (dominated by Fick's lows) commonly exist in sustained‐release materials. Herein, we designed and fabricated two types of film materials to achieve slow, continuous, and long‐term release of small molecules using methyl orange (MO) as a target release substance. B‐MO@polymer films were obtained by embedding MO into polylactic acid/polyethylene glycol (PLA/PEG) substrate and then assembling a layered double hydroxide (LDH)/carboxymethyl chitosan (CMC) barrier layer on the substrate surface. Another type of film (LDH&MO@polymer) was prepared by blending LDH and MO into the PLA/PEG polymer matrix. These films show high loading capacities of ~500 μg/cm2 for MO and display long‐acting sustained‐release property arising from the barrier effect of LDH nano‐brick. Specifically, for the B‐MO@polymer film, the release time of 50% MO is 10 days and the release time of 80% MO can be extended to 30 days. Ultimately, the time for complete release (>96%) reaches over 60 days. By using LDH‐embedded polymer as carriers for active molecules, the zero‐order release of MO was realized for LDH&MO@polymer films, achieving sustained release within as long as 145 days. This work provides a new paradigm to achieve the long‐acting sustained‐release of active molecules through the barrier effect of 2D nano‐bricks.Highlight Two types of films were obtained to achieve long‐term release of small molecules. The films show high loading capacities for active molecules. The long‐acting property is derived from the barrier effect of 2D nano‐brick. The films can be produced in a large scale and have good application prospects.

MPEG-PDLLA polymeric micelles loading a novel pyridazinone derivative IMB5036 for improving anti-tumor activity in hepatocellular carcinoma

IMB5036 (N7) is a hydrophobic pyridazinone compound with antitumor activity, identified in our laboratory. To increase its water solubility, we utilized nanomicelles encapsulating N7 in this study. Monomethyl polyethylene glycol-polylactic acid (mPEG-PDLLA) polymer micelles were employed as drug carrier, and their characterizations were measured. IMB5036/mPEG-PDLLA (N7M) exhibited a particle size of approximately 28 nm and a polydispersity index of around 0.2. The optimal dosage ratio of N7 to mPEG-PDLLA was determined to be 10:90, with an encapsulation rate of (93.66 ± 3.94)% and a drug loading efficiency of (9.59 ± 1.26)%. The morphology of N7 micelles was spherical, with a uniform particle size distribution and good water solubility of approximately 1.17 mg/ml. Compared to the free drug, N7M demonstrated a higher tumor cell uptake rate and slow release profile, while maintaining similar tumor cell killing ability and apoptosis-inducing capacity. In vivo experiments confirmed that the nanomicelles improved tumor targeting, and N7M effectively inhibited tumor growth in a hepatoma xenograft model. Overall, N7M represents a successful injectable nanomicelle formulation for the treatment of hepatoma.

Design of biocompatible polylactic acid–polyethylene glycol combination for manufacturing biodegradable staplers

AbstractFor the development of an effective and faster wound closure method, it is necessary to overcome current techniques' limitations. As compared to other methods, biodegradable staples provide superior mechanical properties, reduce scarring, and promote healing faster. Here, polylactic acid (PLA) and polyethylene glycol (PEG) composite staplers produced by solvent casting are presented as a suggestion for rapidly and easily closing wounds. The resulting samples were tested for mechanical properties, contact angle, and degradation properties over 21–90 days in the engineering phase. Selected formulations were moved to the biological phase for in vitro cytotoxicity by MTT assay and the in vivo biocompatibility assessment by transplantation of the samples into rats' back muscle. The tissue samples were collected and evaluated using hematoxylin and eosin and trichrome staining 1, 6, and 12 weeks after transplantation. When considering the maximum force tolerance range for PLA–PEG at around 20–58 N and comparing it with comparable commercial products, as well as their degradation rate and hydrophilicity, it was concluded that this combination maintains wound edges together. Cell viability tests demonstrated no cytotoxicity in the samples after 48 and 72 h. Morphological observations indicated some condensations of collagen fibers and no remarkable infiltration of inflammatory cells around the transplanted samples. In conclusion, the combination of PLA and PEG showed suitable mechanical properties, superior hydrophilicity, high biocompatibility and is suitable for medical staplers, and is innovative.

Structure of polymeric nanoparticles encapsulating a drug – pamoic acid ion pair by scanning transmission electron microscopy

Drug-delivery systems based on polymeric nanoparticles are useful for improving drug bioavailability and/or delivery of the active ingredient for example directly to the cancerous tumour. The physical and chemical characterization of a functionalized nanoparticle system is required to measure drug loading and dispersion but also to understand and model the rate and extent of drug release to help predict performance. Many techniques can be used, however, difficulties related to structure determination and identifying the precise location of the drug fraction make mathematical prediction complex and in many published examples the final conclusions are based on assumptions regarding an expected structure. Cryogenic scanning transmission electron microscopy imaging in combination with electron energy loss spectroscopy techniques are used here to address this issue and provide a multi-modal approach to the characterisation of a self-assembled polymeric nanoparticle system based upon a polylactic acid - polyethylene glycol (PLA-PEG) block copolymer containing a hydrophobic ion-pair between pamoic acid and an active pharmaceutical ingredient (API). Results indicate a regular dispersion of spherical nanoparticles of 88 ± 9 nm diameter. The particles are shown to have a multi-layer structure consisting of a 25 nm radius hydrophobic core of PLA and pamoic acid-API material with additional enrichment of the pamoic acid-API material within the inner core (that can be off-centre), surrounded by a 9 nm dense PLA-PEG layer all with a low-density PEG surface coating of around 10 nm thickness. This structure suggests that release of the API can only occur by diffusion through or degradation of the dense, 9 nm thick PLA-PEG layer either of which is a process consistent with the previously reported steady release kinetics of the API and counter ion from these nanoparticle formulations. Establishing accurate measures of product structure enables a link to performance by providing appropriate physical parameters for future mathematical modelling of barriers controlling API release in these nanoparticle formulations.

Soft, strong, and breathable polylactic acid/polyethylene glycol microfibrous membranes with a fluffy alignment structure for skin contactor

Polylactic acid (PLA) microfibrous membranes, having high comfort and wearability features, have attracted considerable research interest for applications involving skin contactors. However, the poor softness and low strength of these membranes are the major challenges that prevent their large-scale fabrication and application. Herein, an advanced strategy for preparing a soft, strong, and breathable polylactic acid/polyethylene glycol (PLA/PEG) microfibrous membrane using an in situ drafting-assisted melt-blowing process has been developed. The introduction of PEG significantly improved the crystallization and plasticization of the PLA chain molecules, thus promoting the perfect crystallinity of the PLA phase. Benefiting from the synergy of the PEG and the drafting process, the prepared PLA/PEG microfibrous membranes exhibited a fluffy structure wherein the air permeability increased to 142.5 mm/s with the increase in DCD to 37 cm. Meanwhile, the PLA/PEG microfibrous membranes exhibit optimized anisotropic softness performance: a smaller maximum resistance of 0.13 N in the machine direction and a larger maximum resistance of 1.8 N in the cross direction were obtained in comparison with conventional membranes. This suggests the tremendous potential for using the fabricated membranes in flexible, breathable, and wearable skin contactors.

Obtaining poly (lactic acid) nanofibers encapsulated with peppermint essential oil as potential packaging via solution-blow-spinning

The development of active packaging based on biodegradable material and incorporating active compounds, such as essential oil, is a new technique to ensure food safety without harming the environment. In this study, nanofiber mats of poly (lactic acid)/ polyethylene glycol (PLA/PEG) blend incorporated with peppermint essential oil (PO) at different ratios (5–20 % v/w) were produced by solution-blow-spinning (SBS) for potential packaging application. Electron microscopy showed a cylindrical and interlaced morphology for PLA/PEG/PO and a significant increase in the diameter (139–192 nm) of the nanofibers by increasing PO content. All nanofibers showed high thermal stability (278–345 °C) suitable for use in the food industry. Nuclear magnetic resonance (13C NMR) spectrum confirmed PO in the nanofibers after SBS. ATR-FTIR spectral analysis supported the chemical composition of the nanofiber mats. PO addition led to obtaining hydrophobic nanofibers, enhancing the contact angle to 122° and decreasing water vapor permeability (60 % reduction compared to the PLA/PEG (3.0 g.mm.kPa−1.h−1.m−2). Although the PLA/PEG/20%PO nanofibers did not show halo formation in 24 h, they effectively extended the strawberries' shelf-life at 25 °C, evidencing PO release over time. It also reduced weight loss (2.5 % and 0.3 % weight loss after 5 days for PLA/PEG and PLA/PEG/20%PO, respectively) and increased firmness (8–12 N) for strawberries packed with the nanofiber mats. It is suggested that PLA/PEG films incorporating PO may be used as an active, environmentally friendly packaging material.

Nanocarrier of Pin1 inhibitor based on supercritical fluid technology inhibits cancer metastasis by blocking multiple signaling pathways.

Cancer metastasis is the primary cause of all cancer-related deaths due to the lack of effective targeted drugs that simultaneously block multiple signaling pathways that drive the dissemination and growth of cancer cells. The unique proline isomerase Pin1 activates numerous cancer pathways, but its role in cancer metastasis and the inhibitory efficacy of Pin1 inhibitors on cancer metastasis are unknown. Moreover, the applicability of Pin1 inhibitor-all-trans retinoic acid (ATRA) is limited due to its several drawbacks. Herein, uniform ATRA-loaded polylactic acid-polyethylene glycol block copolymer nanoparticles (ATRA-NPs) with high encapsulation efficiency, good cellular uptake, excellent controlled release performance and pharmacokinetics are developed using supercritical carbon dioxide processing combined with an optimized design. ATRA-NPs exhibited excellent biosafety and significant inhibition on the growth and metastasis of hepatocellular carcinoma. Pin1 played a key role in cancer metastasis and was the main target of ATRA-NPs. ATRA-NPs exerted their potent anti-metastatic effect by inhibiting Pin1 and then simultaneously blocking multiple signaling pathways and cancer epithelial-mesenchymal progression. Since ATRA-NPs could effectively couple the inhibition of cancer cell dissemination with cancer growth, it provided a novel therapeutic strategy for efficiently inhibiting cancer metastasis.

Astaxanthin-loaded nanoparticles enhance its cell uptake, antioxidant and hypolipidemic activities in multiple cell lines

Astaxanthin is a natural carotenoid pigment, which provides many benefits to human health and nutrition. However, the human body has a low bioavailability of astaxanthin due to its poor solubility in the water phase. This study aimed to prepare astaxanthin nanoparticles using an emulsification/solvent evaporation method and then to evaluate bioavailability of nano-astaxanthin for biomedical applications. The results showed that the combinative use of cremophor RH40 as surfactants and polyethylene glycol–polylactic acid copolymer as an encapsulation agent generated well-defined astaxanthin nanoparticles with 5% astaxanthin content. These nanoparticles exhibited spherical morphology with average particle diameters of 90 nm. Nanoastaxanthin had high DPPH free radical scavenging activity and significantly improved cell uptake compared to the free astaxanthin. Astaxanthin nanoparticles showed no cytotoxicity against HT29, HepG2 and RAW264.7 cells up to a concentration of 500 μg/mL and event showed a more powerful cytoprotective effect on H2O2-induced oxidative HepG2 cell damage at concentrations of 50 and 100 μg/mL. Besides that, the activity of antioxidant enzymes (catalase and glutathione peroxidase) and gene expressions of Nrf2, HO-1 and NQO1 increased concentration-dependently, while the mRNA level of Keap1 significantly decreased in cells incubated with nanoastaxanthin compared to astaxanthin and control groups. Moreover, hepatocytes and murine RAW264.7 macrophages treated with nanoastaxanthin, but not with free astaxanthin, displayed to reduce cellular lipid accumulation compared with control cells via altering the expression of key genes in lipid metabolism (LDLR, CYP7A1, FAS, PPARα, CPT-1 and LXRα in HepG2 cells and ABCA1 and G1 in RAW264.7 cells). Our results highlight the great potential of nanoastaxanthin for applications in human health and nutrition.

Sandwich-like scaffold for effective hemostasis and anti-adhesion in cardiac injury

Blood vessels are fully lined on the heart and sternum. Massive bleeding following heart surgery significantly reduces the effectiveness of anti-adhesion materials, resulting in severe tissue adhesion. Adverse outcomes in the follow-up surgery can also be brought on by post-operative adhesion. In this study, a sandwich-like scaffold was developed. Hemostatic sponges made of sodium carboxymethyl cellulose make up the top and bottom layers. An anti-adhesion fibrous membrane with poly-lactic-co-glycolic acid and polyethylene glycol-polylactic acid block copolymer made up the intermediate layer. As a physical barrier, the intermediate layer preserved the morphological integrity for more than a week. Following hemostasis, the layers of the sponges and the blood clot may degrade quickly, reducing the inflammation and fibrin deposition around the wound. This sandwich-like scaffold potentially has hemostasis and anti-adhesion properties that lower the activation level of coagulation factors and lessen bleeding.

The effect of polyethylene glycol on printability, physical and mechanical properties and osteogenic potential of 3D-printed poly (l-lactic acid)/polyethylene glycol scaffold for bone tissue engineering

One of the challenges in critical size bone defect repairing is the use of a porous degradable scaffold with appropriate properties to the host tissue. Nowadays, the three-dimensional (3D) printing method can produce custom and personalized scaffolds and overcome the problems of traditional methods by controlling the porosity and dimensions of biomaterial scaffolds. In this study, polylactic acid/polyethylene glycol (PLA/PEG) scaffolds were prepared with different PEG percentages (0, 5, 10, 15 and 20 wt%) by fused deposition modeling (FDM) to optimize printability and achieve suitable physico-mechanical properties and also enhance cellular behavior for bone tissue engineering and actually, this study complements previous studies. Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were employed for chemical, morphological and thermal evaluations, respectively. It was shown that the adding of 20 wt% PEG to PLA 3D printed scaffolds reduced water contact angle (from 78.16 ± 3.27 to 60.00 ± 2.16), and increased surface wettability. The results also showed that the mechanical properties of the printed scaffolds were not significantly reduced by adding 5 and 10 wt% of PEG. The addition of PEG increased the degradability of scaffolds during immersion in phosphate buffer saline (PBS) solution for 8 weeks and PLA/PEG20 scaffold with 50.96 % had the highest rate of degradation. MTT assay showed that none of the studied scaffolds had cytotoxicity against MG-63 cells and increasing the PEG levels to 20 wt%, increased cell viability and adhesion and osteogenic differentiation. According to the obtained physical, mechanical and biological results, PLA/PEG scaffold printed by the FDM method can be an appropriate candidate for use in bone repair applications.

Large-scale preparation of polylactic acid/polyethylene glycol micro/nanofiber fabrics with aligned fibers via a post-drafting melt blown process

Polylactic acid (PLA) micro/nanofiber fabrics with good biodegradability and biocompatibility have wide applications in the medical protective field. However, the poor flexibility, high brittleness, and insufficient mechanical properties of PLA micro/nanofiber fabrics remain challenging. Herein, a polylactic acid/polyethylene glycol (PLA/PEG) micro/nanofiber fabric with aligned fibers was successfully prepared by an inexpensive and straightforward post-drafting melt blown process. The experimental results showed that PEG can reduce the Tg of PLA, improve the mobility of PLA molecular chains, reduce the complex viscosity of PLA/PEG blends, and play a role in plasticization. The PLA/PEG micro/nanofiber fabrics had an aligned micro/nanofibrous structure, and the average fiber diameter was easily adjusted from 10.7 to 4.9 μm by tailoring the melt blown process parameters, i.e., die temperature and hot air temperature. Moreover, the breaking tensile strength increased from 45.06 to 78.73 N in the machine direction (MD), while it increased from 11.87 to 21.89 N in the cross direction (CD), which means that the breaking tensile strength was enhanced significantly by adjusting the die temperature and hot air temperature. Furthermore, the prepared samples showed a high softness score of 82.7, a large synthetic blood contact angle of 125.7°, and an excellent bursting strength of 58.5 N. These PLA/PEG micro/nanofiber fabrics with aligned fibers are ideal candidates for medical protective applications such as surgical gowns, protection suits, masks, and medical bandages.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10965-022-03184-2.

Development and evaluation of PLA based hybrid block copolymeric nanoparticles for systemic delivery of pirarubicin as an anti-cancer agent

Pirarubicin (PIRA) is a semi-synthetic anthracycline derivative that is reported to have lesser toxicity and better clinical outcomes as compared to its parental form doxorubicin (DOX). However, long term use of PIRA causes bone marrow suppression and severe cardiotoxicity to the recipients. Herein, we have developed a biodegradable polymeric nano platform consisting of amphiphilic di-block copolymer methoxy polyethylene glycol-polylactic acid and a hydrophobic penta-block copolymer polylactic acid-pluronic L-61-polylactic acid as a hybrid system to prepare PIRA (& DOX) encapsulated nanoparticles (NPs) with an aim to reduce its off targeted toxicity and enhance therapeutic efficacy for cancer therapy. Prepared PIRA/DOX NPs showed uniform particle size distribution, high encapsulation efficiency and sustained drug release profile. Cytotoxicity evaluation of PIRA NPs against TNBC cells and mammospheres showed its superior anti-cancer activity over DOX NPs. Anti-cancer efficacy of PIRA/DOX NPs was found significantly enhanced in presence of penta-block copolymer which confirmed chemo-sensitising ability of pluronic L-61. Most importantly, encapsulation of PIRA/DOX in the NPs reduced their off targeted toxicity and increased the maximum tolerated dose in BALB/c mice. Moreover, treatment of EAC tumor harbouring mice with PIRA NPs resulted in higher tumor regression as compared with the groups treated with free PIRA, free DOX or DOX NPs. Altogether, the results conclude that prepared PIRA NPs exhibits an excellent anti-cancer therapeutic efficacy and has a strong potential for cancer therapy.

A recombinant chimeric protein of protective antigen and lethal factor from Bacillus anthracis in polymeric nanocapsules showed a strong immune response in mice: a potential high efficacy vaccine against anthrax.

Anthrax is a serious infectious disease caused by Bacillus anthracis, rod-shaped gram-positive bacteria. The disease infects both humans and animals and causes severe illness. Many vaccines have been developed for anthrax, but the vaccine with very high efficacy is yet to be developed. To overcome the problems of efficacy posed by the existing vaccines, a recombinant chimeric fusion protein containing domain 1 of lethal factor (LFD1) and domain 4 of Bacillus anthracis protective antigen (PA4) was used as antigen in copolymeric nanocapsules (NCs). Accordingly, the solvent evaporation double emulsion method was used to produce NCs containing recombinant chimeric fusion protein (LFD1-PA4). Zeta sizer and potential of nanoparticles, nanoparticle loading efficiency, release pattern of recombinant protein, and the possible effect of polylactic acid-polyethylene glycol (PLA-PEG) nanoparticle production method were investigated. Mice were used to test and evaluate the immune response. The mean titer of antibody produced against loaded LFD1-PA4 compared to free form showed a significant difference. The difference in antibody titer between the groups of once injected, twice injected, and free antigen was significant, and the highest antibody titer was found in the mice twice injected. In addition, a single-time loaded injection showed significantly higher antibodies than the free form injection indicating that loaded LFD1-PA4 into PLA-PEG nanoparticles elicits a stronger immune response. This study showed that LFD1-PA4 fusion protein from Bacillus anthracis served as an active antigen in mice. Also, the nanocarrier (PLA-PEG) containing the antigen can stimulate the immune system in the mice, owing to their controlled release property.

Study some specifications of copolymer (PLA-PEG)

This study about the blends of Poly Lactic Acid/ Poly Ethylene Glycol (PLA/PEG) 4000 copolymer at concentrations (9%,6%,3%,0%)) wt%) from (PEG) and (PLA) (5%) (w/w) by using casting solvent method to production films. The nonwoven nano fibrous mats were obtained by electro spinning of (PLA/PEG) solutions in chloroform, at weight ratios (70/30) (v/v), respectively. DSC is employed to measure the crystallinity difference between (PLA/PEG) blends and their nonwovens mats. the thermal properties (DSC) of (PLA/PEG) copolymer blends films and electrospun nano fiber mats such as (Tm) melting temperature, (Tg) glass transition temperature, (Tc) crystallization, Xc crystallinity rate and enthalpy . the FTIR test was done for all samples to figure the nature linking between (PLA) and (PEG),the results were that (6%) (w/w) of (PEG) was the optimized rate to apply Electrospinning method , data of DSC test defined that (Tg) and (Tm) were decreased, and that refer to occurrence physicist cross linking between the used substances (Completely miscible blend) when the electrospinning method was applied, also Xc for these nonwoven mats was decreased which has in turn an important effect on the speed of biodegradble for poly lactic acid (PLA).

Characterization of Polylactic/Polyethylene glycol/Bone Decellularized Extracellular Matrix Biodegradable Composite for Tissue Regeneration

Abstract This study focused on evaluating the Polylactic acid /Polyethylene glycol (PLA/PEG) combining with bone decellularized extracellular matrix (bone dECM) as the alternative biodegradable material for tissue regenerative purposes. The casting membranes of pure PLA, PLA/PEG blend, and PLA/PEG combining with 5, 10 and 20 wt% bone dECM particles were fabricated and the characteristics of surface morphology, surface contact angle, thermal properties, cell viability, in vitro osteogenesis, and in vitro biodegradative behaviors were investigated. The improvement in hydrophilic characteristic was found in the developing composite. Following the in vitro degradation test in PBS/lysozyme for 7, 30, 60 and 90 days, the composite with higher ratio of bone dECM particles showed the higher percentage of material weight loss. However, the statistically significant of material weight alteration was observed only on the PLA/PEG/20wt% bone dECM after degradation test for 90 days (P ≤0.05). All specimens showed the physically intact at the end of the 90-day in vitro hydrolytic degradation test. The metabolic activities of L929 cells were significantly enhanced by the presence of PLA/PEG/bone dECM composites comparing to pure PLA (P ≤ 0.05). The result from Alizarin red S staining confirmed the osteo-inductive property of developing composite. The present study addressed the promising potential of PLA/PEG/bone dECM composites for applying as an alternative biodegradable material in tissue regenerative purpose. Keywords: Biomaterial, Biodegradable Composite, Bone Decellularized Extracellular Matrix, Polylactic Acid

Emerging uses of PLA-PEG copolymer in cancer drug delivery.

Traditional therapies need high systematic dosages that not only destroys cancerous cells but also healthy cells. To overcome this problem recent advancement in nanotechnology specifically in nanomaterials has been extensively done for various biological applications, such as targeted drug delivery. Nanotechnology, as a frontier science, has the potential to break down all the obstacles to be more effective and secure drug delivery system. It is possible to develop nanopolymer based drug carrier that can target drugs with extreme accuracy. Polymers can advance drug delivery technologies by allowing controlled release of therapeutic drugs in stable amounts over long duration of time. For controlled drug delivery, biodegradable synthetic polymers have various benefits over non-biodegradable polymers. Biodegradable polymer either are less toxic or non-toxic. Polylactic Acid (PLA) is one of the most remarkable amphipathic polymers which make it one of the most suitable materials for polymeric micelles. Amphiphilic nanomaterial, such as Polyethylene Glycol (PEG), is one of the most promising carrier for tumor targeting. PLA-PEG as a copolymer has been generally utilized as drug delivery system for the various types of cancer. Chemotherapeutic drugs are stacked into PLA-PEG copolymer and as a result their duration time delays, hence medications arrive at specific tumor site.

Evaluation of Loco-Regional Skin Toxicity Induced by an In Situ Forming Depot after a Single Subcutaneous Injection at Different Volumes and Flow Rates in Göttingen Minipigs.

The present study aims to investigate the loco-regional tolerability and injection parameters (i.e., flow rate and administration volume) of an in situ forming depot (ISFD) in Göttingen minipigs, to secure both the therapeutic procedure and compliance in chronic medical prescriptions. The ISFD BEPO® technology (MedinCell S.A.) is investigated over 10 days, after a single subcutaneous injection of test item based on a DMSO solution of diblock and triblock polyethylene glycol-polylactic acid copolymers. Injection sites are systematically observed for macroscopic loco-regional skin reactions as well as ultrasound scanning, enabling longitudinal in vivo imaging of the depot. Observations are complemented by histopathological examinations at 72 h and 240 h post-injection. Overall, no treatment-emergent adverse effects are macroscopically or microscopically observed at the subcutaneous injection sites, for the tested injection flow rates of 1 and 8 mL/min and volumes of 0.2 and 1 mL. The histopathology examination confirms an expected foreign body reaction, with an intensity depending on the injected volume. The depot morphology is similar irrespective of the administration flow rates. These results indicate that the ISFD BEPO® technology can be considered safe when administered subcutaneously in Göttingen minipigs, a human-relevant animal model for subcutaneous administrations, in the tested ranges.

Preparation of Polyethylene Glycol-Poly Lactic Acid Water-Soluble Nano-Particles and Its Effect on the Proliferation, Metastasis, and Angiogenesis of Liver Cancer Cells

The onset of the disease is secretive, and the accuracy of early diagnosis is not high. Patients will lose the opportunity of surgical treatment because of severe liver cirrhosis and cancer cell metastasis. Vanib nano-drug was prepared in this study by a polymer, which was used for in vitro research of liver cancer cells. First, polyethylene glycol (PEG)-poly lactic acid (PLA) and Vanib were dissolved in acetone to form a mixed solution, and then, water-soluble nano-particles were obtained by ultrasonic and deionized water. Then, the nano-particles were modified by iRGD and characterized by electron microscopy, DLS, and in vitro release. Besides, CCK-8, flow cytometry apoptosis test, flow cytometry cell cycle test, Transwell cell invasion and metastasis test, and angiogenesis test were applied to detect the effect of the nano-drug on the proliferation, cell metastasis, and angiogenesis of liver cancer cells. The results showed that Vanib nano-particles inhibited the proliferation of liver cancer cells in a dose-dependent manner, and induced apoptosis to G1 block. What’s more, Vanib nano-particles reduced cell viability in a Caspase-dependent manner, thereby inducing cell death. The Vanib nano-particles up-regulated the expression of P21 and also inhibited the cyclins Cyclin E2 and Cycllin B, thereby blocking the cell cycle process. In addition, Vanib nano-particles and free Vanib could inhibit the activity of human umbilical vein endothelial cells (HUVECs) and angiogenesis, which proved that the prepared Vanib nano-particles could effectively curb the growth of liver cancer cells.

Fabrication and Properties of Electrospun and Electrosprayed Polyethylene Glycol/Polylactic Acid (PEG/PLA) Films

Polylactic acid (PLA) film is an alternative filter material for heat-not-burn (HNB) tobacco, but its controllability in cooling performance is limited. In this work, polyethylene glycol (PEG) was introduced to form a polyethylene glycol/polylactic acid (PEG/PLA) film by electrospinning or electrospraying techniques to enhance the cooling performance, due to its lower glass transition and melting temperatures. The PEG/PLA films with typical electrospun or electrosprayed morphologies were successfully fabricated. One typical endothermic peak at approximately 65 °C was clearly observed for the melting PEG phase in the heating process, and the re-crystallization temperature represented by an exothermic peak was effectively lowered to 90–110 °C during the cooling process, indicating that the cooling performance is greatly enhanced by the introduction of the PEG phase. Additionally, the wetting properties and adsorption properties were also intensively studied by characterizing the contact angles, and the as-prepared PEG/PLA films all showed good affinity to water, 1,2-propandiol and triglyceride. Furthermore, the PEG/PLA film with a PLA content of 35 wt.% revealed the largest elasticity modulus of 378.3 ± 68.5 MPa and tensile strength of 10.5 ± 1.1 MPa. The results achieved in this study can guide the development of other filter materials for HNB tobacco application.

Study on the Application of a Novel Nano-Curcumin Drug for Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disease hallmarked by impaired cognitive function and memory decline; it is accompanied by a variety of mental symptoms and behavioral disorders. This disease has a serious impact on society, families, and the afflicted patients. Curcumin (Cur) nanoparticles were preparation by modifying curcumin with polyethylene glycol-polylactic acid (PEG-PLA) amphiphilic block copolymer. The resulting nanodrug can successfully penetrate the blood brain barrier (BBB) and concentrate in the main pathological areas of AD. As measured with a Zeta particle size analyzer, the particle size of PEG-PLA/Cur was 100 ± 0.53 nm, and it was electrically neutral. In vitro experiments revealed that PEG-PLA/Cur successfully penetrated the membrane of PC12 cells and inhibited proliferation. PEG-PLA/Cur also exhibited an inhibitory effect on the production of amyloid β protein (Aβ fiber) and depolymerization activity on Aβ fiber aggregates. PEG-PLA/Cur represents a novel nanodrug with the potential to treat AD.