Drug Delivery Studies Research Articles

Role of nanoparticles in pancreatic drug delivery: Including a bibliography on Targeted drug delivery

The number of times a publication or an individual author has been discussed in the scientific community is a common metric for measuring their impact. The goal of the bibliometric study was to look at the maximum cited articles in the area of "pancreatic cancer, nanoparticles, targeted ligand, binding, drug delivery and treatment.".The database SCOPUS was used to conduct a computerised literature search. The top 100 articles with the most citations were chosen and studied furtherThere were 298 citations in the most cited article, with an average of 62 citations per publication. These highly cited publications appeared in 33 journals, with the Journal of Controlled Release leading the pack (27 articles). The United States contributed 53 articles, which originated from 19 different countries. These 100 citations were provided by 85 institutions, with the “Department of Chemical and Biomolecular Engineering” leading the way (4). The investigation of the top highly cited articles concedes for recognizing significant advances in pancreatic cancer targeted drug delivery study and gives a historical perspective on the advancement of this speciality of cancer research.

Computational fluid-particle dynamics modeling of ultrafine to coarse particles deposition in the human respiratory system, down to the terminal bronchiole

Background and objectivesSuspended respirable airborne particles are associated with human health risks and especially particles within the range of ultrafine (< 0.1 μm) or fine (< 2.5 μm) have a high possibility of penetrating the lung region, which is concerned to be closely related to the bronchial or alveoli tissue dosimetry. Nature complex structure of the respiratory system requires much effort to explore and comprehend the flow and the inhaled particle dynamics for precise health risk assessment. Therefore, this study applied the computational fluid-particle dynamics (CFPD) method to elucidate the deposition characteristics of ultrafine-to-coarse particles in the human respiratory tract from nostrils to the 16th generation of terminal bronchi. MethodsThe realistic bronchi up to the 8th generation are precisely and perfectly generated from computed tomography (CT) images, and an artificial model compensates for the 9th-16th bronchioles. Herein, the steady airflow is simulated at constant breathing flow rates of 7.5, 15, and 30 L/min, reproducing human resting-intense activity. Then, trajectories of the particle size ranging from 0.002 – 10 μm are tracked using a discrete phase model. ResultsHere, we report reliable results of airflow patterns and particle deposition efficiency in the human respiratory system validated against experimental data. The individual-related focal point of ultrafine and fine particles deposition rates was actualized at the 8th generation; whilst the hot-spot of the deposited coarse particles was found in the 6th generation. Lobar deposition characterizes the dominance of coarse particles deposited in the right lower lobe, whereas the left upper-lower and right lower lobes simultaneously occupy high deposition rates for ultrafine particles. Finally, the results indicate a higher deposition in the right lung compared to its counterpart. ConclusionsFrom the results, the developed realistic human respiratory system down to the terminal bronchiole in this study, in coupling with the CFPD method, delivers the accurate prediction of a wide range of particles in terms of particle dosimetry and visualization of site-specific in the consecutive respiratory system. In addition, the series of CFPD analyses and their results are to offer in-depth information on particle behavior in human bronchioles, which may benefit health risk assessment or drug delivery studies

Redox- and pH-responsive alginate-based magnetic hydrogel: “Smart” drug delivery and protein corona studies

A redox- and pH-responsive magnetic hydrogel was designed and developed based on alginate (Alg) through double crosslinking approach for sustained and targeted delivery of doxorubicin (Dox). For this objective, Fe3O4 nanoparticles (NPs) were synthesized by a chemical co-precipitation method, and then their surfaces were modified using an amine-end capped silane coupling agent. Alginate was oxidized using sodium periodate. Then, an alginate-based pH- and redox-responsive magnetic hydrogel with and without Dox loading was synthesized by adding amine-modified Fe3O4 NPs and cystamine (Cys) moiety through “Schiff-Base” condensation followed by double crosslinking with CaCl2. Drug loading and encapsulation efficiencies were quantified as 3.4 ± 0.27 and 83 ± 2.7%, respectively. Drug release study by dialysis method approved pH- and redox-dependent drug release behavior. Interactions between hydrogel and human serum albumin (HSA) was investigated using spectroscopy techniques, and it was found that the developed hydrogel can interact strongly with HSA. The thermodynamic parameters of the protein-hydrogel interaction were also calculated, and it was revealed that interaction process is spontaneous and endothermic. The anti-cancer activity of the developed magnetic DDS was assessed against MCF7 cells by MTT assay. It was found that free Dox had a stronger cytotoxic effect in the first 24 and 48 h in comparison with Dox-loaded DDS, while after 72 h, the DDS showed higher anti-cancer activity, possibly due to the controlled release of drug by the hydrogel over time.

Covalent synthesis, structural characterization and biological behavioral study of tin captured porphyrin-polyoxometalate based polymeric hybrid

The combination of polyoxometalates(POMs) and tin-based porphyrin in a variety of modes ofinteractionturned out to be the key for unlocking new directions in the study of biological activities. In this study, a new sandwich type covalently attached porphyrin C52H48N6O6Sn (SnTPP-Di-Tris) and Anderson POM-porphyrin polymeric hybrid, with molecular formula as [{N(C4H9)4}8{C62H60Mn2Mo12N6O48Sn·CH3CN}](PolySnP@POM). These compounds were clearly characterized and their formation was confirmed by spectroscopic (UV–visible, FT-IR, NMR) techniques, powder XRD, elemental analyses, cyclic voltammetry and scanning electron microscopy techniques(SEM). SnTPP-Di-Tris and PolySnP@POM were evaluated for drug delivery, DNA binding, protein binding and antibacterial studies. It is found that drug loading efficiency was 89% and 93% for PolySnP@POM and SnTPP-Di-Tris, respectively. While drug release was more efficient in acidic media (pH = 3) as 100 % for both compounds in 1.5 h as compared to basic media (pH = 11) 65.93% and 72.6% for SnTPP-Di-Tris and PolySnP@POM, respectively. Uv–visible study of SnTPP-Di-Tris and PolySnP@POM with salmon sperm DNA (SS-DNA) showed hypochromism trend which indicate intercalation mode of attachment and exhibited binding constant value 4.9 × 103 M−1 and 2.7 × 104 M−1 for SnTPP-Di-Tris and PolySnP@POM, respectively, referring that PolySnP@POM has more binding affinity than SnTPP-Di-Tris. Protein binding Study presented binding constant value (Kb) 3.09 × 104 M−1 and 1.30 × 104 M−1 for PolySnP@POM, and SnTPP-Di-Tris, correspondingly. Antibacterial activity results showed minor to significant activity. Furthermore, enhanced antibacterial activity of SnTPP-Di-Tris over its corresponding hybrid PolySnP@POM was observed because of lipophilic and more proliferating nature of SnTPP-Di-Tris.

‘Click’ synthesized calcium-chitosan-triazole nanocomplex from CaC2 as an efficient drug carrier, antimicrobial and antioxidant polymer

A calcium-chitosan-triazole nanocomplex (Ca@CS-Tz) was synthesized via the robust copper catalyzed azide-alkyne cycloaddition using calcium carbide (CaC2) as an in-situ source of acetylene. The nanocomplex was characterized by various techniques and it was proved to be an efficient drug carrier with satisfactory antimicrobial and antioxidant properties. Quercetin loaded nanocomplex (encapsulation efficiency- 68.2 ± 1.0 %) was studied for targeted drug release and the drug release after 120 h was found to be 80.7 ± 0.8 % and 8.69 ± 0.5 % at pH 5.0 and 7.4 respectively. On biological evaluation, the nanocomplex showed enhanced antimicrobial activity against gram-negative bacteria Escherichia coli (E. coli), gram-positive bacteria Bacillus subtilis (B. subtilis) and a fungi Aspergillus niger (A. niger). Moreover, the synthesized Ca@CS-Tz nanocomplex also exhibited significant antioxidant property. Herein, the novel results corresponding to the antimicrobial effect on A. niger and drug delivery studies performed using our previously synthesized chitosan triazole (CS-triazole) derivative have also been reported. Finally, the results of the present study were compared to the results obtained to our previously reported derivative. The incorporation of calcium ions into CS-triazole can lead to the utilization of this complex in various other biomedical applications e.g. bone tissue engineering.

Importance of tautomerism in drugs.

Tautomerism is an important phenomenon exhibited by many drugs. As we discuss in this review, identifying the different tautomers of drugs and exploring their importance in the mechanisms of drug action are integral components of current drug discovery. Nuclear magnetic resonance (NMR), infrared (IR), ultraviolet (UV), Raman, and terahertz spectroscopic techniques, as well as X-ray diffraction, are useful for exploring drug tautomerism. Quantum chemical methods, in association with pharmacoinformatics tools, are being used to evaluate tautomeric preferences in terms of energy effects. Desmotropy (i.e., tautomeric polymorphism) of the drugs is particularly important in drug delivery studies.

Development of the Formulation and Evaluation of the Anti-infl ammatory Activity of Vitex negundo Gel and Latex

Essential oils include Vitex negundo Linn. It is used in the treatment of eye diseases, toothache, redness, white spots, splenomegaly, skin ulcers, catarrh, rheumatoid arthritis, gonorrhea and bronchitis. It is also used as a tonic, insect repellent, emulsifi er, menstrual aid, antibacterial, antipyretic and antihistamine. Preparations from plant parts of V. negundo treat a variety of ailments, including rheumatic diseases, arthritis, gout, cervicitis, infl ammatory diseases of the musculoskeletal system, hemorrhoids (thousands), rheumatic pains, sprains and toothaches. It has been used commercially for miles in various Ayurvedic remedies and ointments to treat wounds, burns, and fungal skin infections. We concluded from in vitro drug delivery studies that latex composed of HPMC polymers facilitates controlled release of drugs over long periods of time, avoids further fl uctuations, and reduces treatment costs. This new class of drug delivery is gaining popularity due to the spreadability, adhesion, viscosity and extrudability properties of emulgel, which makes topical application of hydrophobic pills desirable for every near and systemic eff ect.

Fabrication, characterization, antimicrobial, toxicity and potential drug-delivery studies of PEGylated Sesamum indicum oil based nanoemulsion system

BackgroundThe actively mutating properties of disease-causing pathogens and GI intolerance associated with certain antibiotics among other challenges necessitated the adoption of colloidal system for drug delivery. Nanoemulsions (Ciprofloxacin (Cp) -loaded and non-drug loaded) were prepared by spontaneous emulsification method, characterized using Cryo-TEM, FTIR and Zetasizer. Antimicrobial activities were carried out using agar well diffusion method on Klebsiella pneumoniae and Bacillus subtilis. The in-vitro and dermal toxicological assessment were carried out using adult Wistar rats.ResultsThe Cryo-TEM micrographs showed spherical morphology while zetasizer results showed polydispersity index (PDI), mean droplet size and zeta potential (ZP) of 0.553, 124.3 ± 0.29 nm and − 15.3 mV respectively for non-drug loaded sesame oil-based emulsion (SOAB). While 0.295, 244.8 ± 0.33 nm and − 5.54 mV were recorded for Cp-loaded sesame oil-based emulsion (SOAB + Cp). The effective voltage charge of the emulsions was 147.4 V. FTIR results of Cp recorded O–H adsorption value of 3429 cm−1, while SOAB and SOAB + Cp showed superimposition at 3427.76 cm−1 showing no drug-excipient interactions. No skin irritation was observed after 14 days of skin corrosion assessment. No significant difference (p > 0.05) in body weight gain of both test and control animals, the treatment did not cause any observable alterations in blood-chemistry parameters and hematological indices. Photomicrographs of liver and heart shows an uncompromised histological architecture.ConclusionThe finding of the study shows a skin friendly, nanosized, spherical negatively charged emulsion with no cardiotoxic, hematotoxic and hepatotoxic effects on Wistar rats, and as such appears promising as a safe vehicle for drug delivery.Graphical

Preparation of Three-Dimensional Graphene Oxide Electric-Field/Temperature-Sensitive Hydrogels and Transdermal-Controlled Release Drug Delivery Study

Preparation of Three-Dimensional Graphene Oxide Electric-Field/Temperature-Sensitive Hydrogels and Transdermal-Controlled Release Drug Delivery Study

Thermosensitive Polymer-Modified Mesoporous Silica for pH and Temperature-Responsive Drug Delivery

A mesoporous silica-based drug delivery system (MS@PNIPAm-PAAm NPs) was synthesized by conjugating the PNIPAm-PAAm copolymer onto the mesoporous silica (MS) surface as a gatekeeper that responds to temperature and pH changes. The drug delivery studies are carried out in vitro at different pH (7.4, 6.5, and 5.0) and temperatures (such as 25 °C and 42 °C, respectively). The surface conjugated copolymer (PNIPAm-PAAm) acts as a gatekeeper below the lower critical solution temperature (LCST) (<32 °C) and as a collapsed globule structure above LCST (>32 °C), resulting in controlled drug delivery from the MS@PNIPAm-PAAm system. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cellular internalization results support the prepared MS@PNIPAm-PAAm NPs being biocompatible and readily taken up by MDA-MB-231 cells. The prepared MS@PNIPAm-PAAm NPs, with their pH-responsive drug release behavior and good biocompatibility, could be used as a drug delivery vehicle where sustained drug release at higher temperatures is required.

An interplay of matrix stiffness, dimensionality and adhesivity on cellular behavior

Cell-based assays are essential in vitro tools for understanding basic cell biology, pathophysiology of diseases and mechanism of drug actions most cancer studies have utilized two-dimensional (2D) cell culture methods, which have their shortcomings including lack of cell- extracellular matrix interactions and three-dimensional (3D) geometry, and inaccurate representation of cell polarity. Hence, 3D matrices are being increasingly used to study the effect of 3D niche on cell behavior. Till date, very few systematic studies have been done to show comparison of cell behavior when seeded on the surface and encapsulated inside the matrix. In this study, we fabricated poly(ethylene glycol) (PEG) and gelatin-based matrices using UV mediated photo-polymerization to establish 2D and 3D cell culture methods using breast cancer MDA-MB-231 cells. We have found that the adhesion and spreading of cells on the gel surface is different from that when embedded in gels. The stiffness of poly (ethylene glycol) diacrylate (PEGDA)-gelatin methacryloyl (GelMA) hydrogels with lower concentration of GelMA is lower than that with higher GelMA; further, those with higher overall concentration of polymers (>5%) retain their mechanical integrity and do not degrade even after 7 d. Physical characterization of these matrices demonstrate their optimal pore size, mechanical stiffness and degradation, which are further tunable for tissue engineering, regenerative medicine, drug delivery and cancer studies. Additionally, these semi-synthetic PEGDA-GelMA matrices are transparent in nature, thereby, allowing easy imaging of cells in 3D. The system developed here can be used for short and long term cell culture and can be potentially explored for cell migration and metastasis studies.

Biodistribution of Intratracheal, Intranasal, and Intravenous Injections of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles in a Mouse Model for Drug Delivery Studies

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are extensively studied as therapeutic tools. Evaluation of their biodistribution is fundamental to understanding MSC-EVs' impact on target organs. In our work, MSC-EVs were initially labeled with DiR, a fluorescent lipophilic dye, and administered to BALB/c mice (2.00 × 1010 EV/mice) through the following routes: intravenous (IV), intratracheal (IT) and intranasal (IN). DiR-labeled MSC-EVs were monitored immediately after injection, and after 3 and 24 hours (h). Whole-body analysis, 3 h after IV injection, showed an accumulation of MSC-EVs in the mice abdominal region, compared to IT and IN, where EVs mainly localized at the levels of the chest and brain region, respectively. After 24 h, EV-injected mice retained a stronger positivity in the same regions identified after 3 h from injection. The analyses of isolated organs confirmed the accumulation of EVs in the spleen and liver after IV administration. Twenty-four hours after the IT injection of MSC-EVs, a stronger positivity was detected selectively in the isolated lungs, while for IN, the signal was confined to the brain. In conclusion, these results show that local administration of EVs can increase their concentration in selective organs, limiting their systemic biodistribution and possibly the extra-organ effects. Biodistribution studies can help in the selection of the most appropriate way of administration of MSC-EVs for the treatment of different diseases.

Multifunctional Iron Oxide Nanocarriers Synthesis for Drug Delivery, Diagnostic Imaging, and Biodistribution Study.

The aim of the current study is to design the radiolabeled and drug-loaded nanocarrier with high loading capacity and pH-dependent drug release characteristics that could effectively transport loaded compounds to various organs for efficient diagnostic imaging and chemotherapeutic drug delivery. The aqueous extract of green tea leaves was used to synthesize the small-sized iron oxide nanoparticles (IONPs). The nanoparticles were characterized with UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray analysis (EDX). Iron oxide nanoparticles with sizes smaller than 50nm were successfully synthesized, making them suitable for in vivo studies. In drug loading trials, 94% of the drug was loaded onto the active surface of iron oxide nanoparticles from the solution. The in vitro drug release study revealed that an acidic environment (pH 4.5) effectively triggers the release of doxorubicin (DOX) from the nanoparticles as compared to a neutral environment (pH 7.4). The gamma-emitting radionuclide 99mTc was successfully labeled with IONPs for biodistribution and imaging studies. The efficiency of radiolabeling was observed to be ≥ 99%. Furthermore, the in vivo biodistribution study of radiolabeled IONPs in rabbit model showed rapid accumulation in various organs such as heart, liver, and kidneys. This work suggested that green synthesized iron oxide nanoparticles are potential nanocarriers for diagnostic imaging and efficiently distributing DOX to specific organs. The aqueous extract of green tea leaves was used for the facile green synthesis of iron oxide nanoparticles (IONPs). Furthermore, the chemotherapeutic drug doxorubicin (DOX) and gamma-emitting radionuclide 99mTc were loaded on these iron oxide nanoparticles to evaluate the in vivo biodistribution and drug delivery studies in the rabbit models.

Biophysical study of cisplatin loaded albumin-gold nanoparticle and its interaction with glycans of gp60 receptor

The biophysical study provides a quantitative understanding of biomolecular interaction. The interaction of protein-nanoparticle has been critically examined using various biophysical and biochemical tools. The present investigation focussed on the biophysical characterization of anticancer drug cisplatin (CPT) with Bovine Serum Albumin (BSA) - Gold nanoparticles (GNP) conjugate; and BSA-CPT-GNP interaction with glycan sugars of glycoprotein receptor. Spectroscopic study (UV visible and fluorescence) showed strong binding of CPT loaded BSA with GNP. The binding between BSA-CPT-GNP and glycan sugars of gp60 receptor was estimated. Circular Dichroism (CD) spectroscopy study revealed weak alteration in the secondary structure of BSA upon CPT and GNP binding. Dynamic Light Scattering (DLS) data indicated the changes in the size of conjugates; zeta potential data showed the stability of conjugates. Biocompatible studies showed no toxicity to RBCs and chorioallantoic membrane (CAM). The mechanisms of interaction have been explored at the molecular and cellular levels. This investigation can be effectively extrapolated for in-vivo and in-vitro targeted drug delivery studies for cancer therapy.

Pharmacokinetic Study of Triptolide Nanocarrier in Transdermal Drug Delivery System-Combination of Experiment and Mathematical Modeling.

Compared with traditional oral and injection administration, the transdermal administration of traditional Chinese medicine has distinctive characteristics and advantages, which can avoid the "first pass effect" of the liver and the destruction of the gastrointestinal tract, maintain a stable blood concentration, and prolong drug action time. However, the basic theory and technology research in transdermal drug delivery are relatively limited at present, especially regarding research on new carriers of transdermal drug delivery and pharmacokinetic studies of the skin, which has become a bottleneck of transdermal drug delivery development. Triptolide is one of the main active components of Tripterygium wilfordii, which displays activities against mouse models of polycystic kidney disease and pancreatic cancer but its physical properties and severe toxicity limit its therapeutic potential. Due to the previously mentioned advantages of transdermal administration, in this study, we performed a detail analysis of the pharmacokinetics of a new transdermal triptolide delivery system. Triptolide nanoemulsion gels were prepared and served as new delivery systems, and the ex vivo characteristics were described. The metabolic characteristics of the different triptolide transdermal drug delivery formulations were investigated via skin-blood synchronous microdialysis combined with LC/MS. A multiscale modeling framework, molecular dynamics and finite element modeling were adopted to simulate the transport process of triptolide in the skin and to explore the pharmacokinetics and mathematical patterns. This study shows that the three-layer model can be used for transdermal drug delivery system drug diffusion research. Therefore, it is profitable for transdermal drug delivery system design and the optimization of the dosage form. Based on the drug concentration of the in vivo microdialysis measurement technology, the diffusion coefficient of drugs in the skin can be more accurately measured, and the numerical results can be verified. Therefore, the microdialysis technique combined with mathematical modeling provides a very good platform for the further study of transdermal delivery systems. This research will provide a new technology and method for the study of the pharmacokinetics of traditional Chinese medicine transdermal drug delivery. It has important theoretical and practical significance in clarifying the metabolic transformation of percutaneous drug absorption and screening for appropriate drugs and dosage forms of transdermal drug delivery.

Advances in BBB on Chip and Application for Studying Reversible Opening of Blood-Brain Barrier by Sonoporation.

The complex structure of the blood-brain barrier (BBB), which blocks nearly all large biomolecules, hinders drug delivery to the brain and drug assessment, thus decelerating drug development. Conventional in vitro models of BBB cannot mimic some crucial features of BBB in vivo including a shear stress environment and the interaction between different types of cells. There is a great demand for a new in vitro platform of BBB that can be used for drug delivery studies. Compared with in vivo models, an in vitro platform has the merits of low cost, shorter test period, and simplicity of operation. Microfluidic technology and microfabrication are good tools in rebuilding the BBB in vitro. During the past decade, great efforts have been made to improve BBB penetration for drug delivery using biochemical or physical stimuli. In particular, compared with other drug delivery strategies, sonoporation is more attractive due to its minimized systemic exposure, high efficiency, controllability, and reversible manner. BBB on chips (BOC) holds great promise when combined with sonoporation. More details and mechanisms such as trans-endothelial electrical resistance (TEER) measurements and dynamic opening of tight junctions can be figured out when using sonoporation stimulating BOC, which will be of great benefit for drug development. Herein, we discuss the recent advances in BOC and sonoporation for BBB disruption with this in vitro platform.

Development of 3D‐printed devices for the study of transscleral drug delivery on freshly excised whole porcine eyes

AbstractPurpose: Ex vivo ocular models are a valuable tool for quick screening ophthalmic formulations through permeation and retention studies. We hereby present a 3D‐printed set‐up consisting of a combination of two devices, allowing for the ex vivo study of transscleral drug delivery with fresh whole swine eyes.Methods: The two devices were drafted on a CAD (computer aided design) software and 3D printed with three different printing techniques: selective laser sintering (SLS), fused deposition modelling (FDM) and masked stereolithography (MSLA). The first device was designed to guarantee the contact between drug formulation (liquid or semisolid) and the scleral surface in a defined permeation area for up to 24 h. The second device was then designed to maintain up to three ocular bulbs at constant temperature (37°C) and humidity values.Results: MSLA 3D printing technique was selected due to its versatility, superior print detail and a low unitary cost. In addition, the other two explored techniques delivered relatively porous prints that do not guarantee the required water and air tightness of the devices. The first device was optimized in order to maximize adherence onto the scleral surface and thus anatomically adjusted to porcine scleral curvature. Firm anchorage onto the ocular surface was achieved through a ring‐shaped vacuum chamber easily controlled with a syringe. The second device allowed to immobilize the ocular bulb during the experiment, preserve ocular hydration, and maintain a fixed working temperature by placement into a water bath.Conclusions: The developed ex vivo set‐up, based on the whole porcine eye, could be suitable to perform permeation and accumulation studies of transscleral applied ocular formulations.

Electrochemically Enhanced Delivery of Pemetrexed from Electroactive Hydrogels.

Electroactive hydrogels based on derivatives of polyethyleneglycol (PEG), chitosan and polypyrrole were prepared via a combination of photopolymerization and oxidative chemical polymerization, and optionally doped with anions (e.g., lignin, drugs, etc.). The products were analyzed with a variety of techniques, including: FT-IR, UV-Vis, 1H NMR (solution state), 13C NMR (solid state), XRD, TGA, SEM, swelling ratios and rheology. The conductive gels swell ca. 8 times less than the non-conductive gels due to the presence of the interpenetrating network (IPN) of polypyrrole and lignin. A rheological study showed that the non-conductive gels are soft (G' 0.35 kPa, G″ 0.02 kPa) with properties analogous to brain tissue, whereas the conductive gels are significantly stronger (G' 30 kPa, G″ 19 kPa) analogous to breast tissue due to the presence of the IPN of polypyrrole and lignin. The potential of these biomaterials to be used for biomedical applications was validated in vitro by cell culture studies (assessing adhesion and proliferation of fibroblasts) and drug delivery studies (electrochemically loading the FDA-approved chemotherapeutic pemetrexed and measuring passive and stimulated release); indeed, the application of electrical stimulus enhanced the release of PEM from gels by ca. 10-15% relative to the passive release control experiment for each application of electrical stimulation over a short period analogous to the duration of stimulation applied for electrochemotherapy. It is foreseeable that such materials could be integrated in electrochemotherapeutic medical devices, e.g., electrode arrays or plates currently used in the clinic.

Improving Swimming Performance of Photolithography-Based Microswimmers Using Curvature Structures.

The emergence of robotic microswimmers and their huge potential in biomedical applications such as drug delivery, non-invasive surgery, and bio-sensing facilitates studies to improve their effectiveness. Recently, achiral microswimmers that have neither flexible nor helical structures have garnered attention because of their simple structures and fabrication process while preserving adequate swimming velocity and controllability. In this paper, the crescent shape was utilized to create photolithography-fabricated crescent-shaped achiral microswimmers. The microswimmers were actuated using rotating magnetic fields at low Reynolds numbers. Compared with the previously reported achiral microswimmers, the crescent-shaped microswimmers showed significant improvement in forward swimming speed. The effects of different curvatures, arm angles, and procession angles on the velocities of microswimmers were investigated. Moreover, the optimal swimming motion was defined by adjusting the field strength of the magnetic field. Finally, the effect of the thickness of the microswimmers on their swimming velocity was investigated.

Targeted delivery of harmine to xenografted human pancreatic islets promotes robust cell proliferation

Type 1 diabetes (T1D) occurs as a consequence of the autoimmune destruction of insulin-producing pancreatic beta (β) cells and commonly presents with insulin deficiency and unregulated glycemic control. Despite improvements in the medical management of T1D, life-threatening complications are still common. Beta-cell replication to replace lost cells may be achieved by using small-molecule mitogenic drugs, like harmine. However, the safe and effective delivery of such drugs to beta cells remains a challenge. This work aims to deploy an antibody conjugated nanocarrier platform to achieve cell-specific delivery of candidate therapeutic and imaging agents to pancreatic endocrine cells. We approached this goal by generating core–shell type micellar nanocarriers composed of the tri-block copolymer, Pluronic®F127 (PEO100–PPO65–PEO100). We decorated these nanocarriers with a pancreatic endocrine cell-selective monoclonal antibody (HPi1), with preference for beta cells, to achieve active targeting. The PPO-based hydrophobic core allows encapsulation of various hydrophobic cargoes, whereas the PEO-based hydrophilic shell curbs the protein adhesion, hence prolonging the nanocarriers' systemic circulation time. The nancarriers were loaded with quantum dots (QDots) that allowed nanocarrier detection both in-vitro and in-vivo. In-vitro studies revealed that HPi1 conjugated nanocarriers could target endocrine cells in dispersed islet cell preparations with a high degree of specificity, with beta cells exhibiting a fluorescent quantum dot signal that was approximately five orders of magnitude greater than the signal associated with alpha cells. In vivo endocrine cell targeting studies demonstrated that the HPi1 conjugated nanocarriers could significantly accumulate at the islet xenograft site. For drug delivery studies, the nanocarriers were loaded with harmine. We demonstrated that HPi1 conjugated nanocarriers successfully targeted and delivered harmine to human endocrine cells in a human islet xenograft model. In this model, targeted harmine delivery yielded an ~ 41-fold increase in the number of BrdU positive cells in the human islet xenograft than that observed in untreated control mice. By contrast, non-targeted harmine yielded an ~ 9-fold increase in BrdU positive cells. We conclude that the nanocarrier platform enabled cell-selective targeting of xenografted human pancreatic endocrine cells and the selective delivery of the hydrophobic drug harmine to those cells. Further, the dramatic increase in proliferation with targeted harmine, a likely consequence of achieving higher local drug concentrations, supports the concept that targeted drug delivery may promote more potent biological responses when using harmine and/or other drugs than non-targeting approaches. These results suggest that this targeted drug delivery platform may apply in drug screening, beta cell regenerative therapies, and/or diagnostic imaging in patients with type 1 diabetes.