Delivery Applications Research Articles

Assessing Lymphatic Uptake of Lipids Using Magnetic Resonance Imaging: A Feasibility Study in Healthy Human Volunteers with Potential Application for Tracking Lymph Node Delivery of Drugs and Formulation Excipients.

Dietary lipids and some pharmaceutical lipid excipients can facilitate the targeted delivery of drugs to the intestinal lymphatics. Here, the feasibility of magnetic resonance imaging (MRI) for imaging lipid uptake into the intestinal lymphatics was assessed, shedding light on which lymph nodes can be targeted using this approach. Three healthy male volunteers were scanned at 3.0 T at baseline, 120, 180, 240, and 300 min post high-fat meal. A sagittal multi-slice image was acquired using a diffusion-weighted whole-body imaging sequence with background suppression (DWIBS) (pre inversion TI = 260 ms). Changes in area, major, and minor axis length were compared at each time point. Apparent diffusion coefficient (ADC) was calculated (b = 0 and 600 s/mm2) across eight slices. An average of 22 nodes could be visualised across all time points. ADC increased at 120 and 180 min compared to the baseline in all three participants by an average of 9.2% and 6.8%, respectively. In two participants, mean node area and major axis lengths increased at 120 and 180 min relative to the baseline. In conclusion, the method described shows potential for repeated lymph node measurements and the tracking of lipid uptake into the lymphatics. Further studies should focus on methodology optimisation in a larger cohort.

Learning Strategies at SD 8 Muhammadiyah Reinforcement during the Covid-19 Pandemic

This research is motivated by the regulation of the Ministry of Education and Culture regarding the implementation of education during Covid-19 pandemic which requires the implementation of distance learning using online learning media. The purpose of this study was to find out the history of school formation, differences in learning before and after pandemic, challenges faced and learninf strategies implemented by SD 8 Muhammadiyah Tulangan during Covid-19 pandemic. The method used is qualitative with the observation, interview, question and answer. The results of thsi study can be concluded that SD 8 Muhammadiyah has a combination of learning strategies between face to face learning and online learning or what is commonly referred to blended learning method. The blended learning methods that is implemented in SD 8 Muhammadiyah Sidoarjo are conducting learning activities through zoom application for better material delivery and conducting study visits to students’ homes directly to share opinions and views between teacher, parents, and students as well as to find out advantages and disadvantages of online learning so far.

MWNTs or PEG as Stability Enhancers for DNA-Cationic Surfactant Gel Particles.

Cationic surfactants interact with DNA (Deoxyribonucleic acid), forming surfactant-DNA complexes that offer particularly efficient control for encapsulation and release of DNA from DNA gel particles. In the present work, DNA-based particles were prepared using CTAB (Cetyltrimethylammonium bromide) as the cationic surfactant and modified using two different additives: (Multi-Walled Carbon Nanotubes) MWNT or PEG (Poly Ethylene Glycol). The use of both additives to form composites increased the stability of the gel particles. The stability was monitored by the release of DNA and CTAB in different pH solutions. However, not much is known about the influence of pH on DNA–surfactant interaction and the release of DNA and surfactant from gel particles. It was observed that the solubilization of DNA occurs only in very acid media, while that of CTAB does not depend on pH and gets to a plateau after about 8 h. Within 2 h in contact with a pH = 2 solution, about 1% DNA and CTAB was released. Complete destruction for the gel particles was observed in pH = 2 solution after 17 days for PEG and 20 days for MWNT. The composite particles show a considerably enlarged sustained release span compared to the unmodified ones. The dehydration-rehydration studies show that the structure of the composite gel particles, as determined from SAXS (Small-Angle-X-Ray-Scattering) experiments, is similar to that of the unmodified ones. These studies will allow a better knowledge of these particles’ formation and evolution in view of possible applications in drug delivery and release.

A Comprehensive Review on Microbubble Concept, Development and Its Application in Therapeutic Drug Delivery and Clinical Management of Disease.

The general purpose of this review was to briefly describe the Gastro-Retentive Drug Delivery System (GRDDS) and to primarily focus on mechanisms of flotation for gastric retention. The principle mechanism of Floating Drug Delivery Systems (FDDS) is mainly based on hydro-dynamically controlled low-density system, which gets swollen when comes in contact with the gastric environment and remains buoyant for an extended period of time with improved bioavailability and therapeutic efficacy. The main perspective of this review was to focus on microbubble drug delivery due to its wide range of applications. Microbubble is a new, economically viable, and non-invasive technique that is alternative to conventional techniques. The size of microbubbles ranges from 1-100 micrometers, which contain oxygen or air and remain suspended for prolonged drug release. Due to its great potential, microbubble is used in the therapeutic delivery of drug molecules or genetic material at their specific targeted site in various diseases. The recent research also suggests that ultrasound-mediated microbubble is more frequently used in the biomedical field for imaging of site-specific molecule targeting for the detection of disease and site-specific drug delivery. Gastro-retentive floating drug delivery system was considered as the most favorable approach for site-specific drug delivery. But nowadays, microbubble is gaining more popularity for its potential applications in the biomedical field. In recent years, there is much progress in microbubble for site-specific delivery of a drug or genetic material. Recent research also suggests that the ultrasound- mediated microbubble has shown a positive impact on the diagnosis and clinical management of various diseases such as liver cirrhosis, brain tumor, ocular, and urinary tract infection.

Identification and physical characterization of a spontaneous mutation of the tobacco mosaic virus in the laboratory environment

Virus-like particles are an emerging class of nano-biotechnology with the Tobacco Mosaic Virus (TMV) having found a wide range of applications in imaging, drug delivery, and vaccine development. TMV is typically produced in planta, and, as an RNA virus, is highly susceptible to natural mutation that may impact its properties. Over the course of 2 years, from 2018 until 2020, our laboratory followed a spontaneous point mutation in the TMV coat protein—first observed as a 30 Da difference in electrospray ionization mass spectrometry (ESI–MS). The mutation would have been difficult to notice by electrophoretic mobility in agarose or SDS-PAGE and does not alter viral morphology as assessed by transmission electron microscopy. The mutation responsible for the 30 Da difference between the wild-type (wTMV) and mutant (mTMV) coat proteins was identified by a bottom-up proteomic approach as a change from glycine to serine at position 155 based on collision-induced dissociation data. Since residue 155 is located on the outer surface of the TMV rod, it is feasible that the mutation alters TMV surface chemistry. However, enzyme-linked immunosorbent assays found no difference in binding between mTMV and wTMV. Functionalization of a nearby residue, tyrosine 139, with diazonium salt, also appears unaffected. Overall, this study highlights the necessity of standard workflows to quality-control viral stocks. We suggest that ESI–MS is a straightforward and low-cost way to identify emerging mutants in coat proteins.

SEARCH AND JUSTIFICATION OF WAYS TO INCREASE THE UNITIZED CARGO TRANSPORTATION EFFICIENCY

Purpose. Identification and methodological substantiation of ways to increase the unitized cargo transportation efficiency, which would increase the trucking company profits and the manufacturer quality customer service. Methodology. In the course of the research the following methods were used: the method of theoretical generalization and systematization to determine the peculiarities of formation of the rational routes of cargo transportation in different conditions; the analytical method to determine the factors influencing the feasibility of adopting a certain strategy of the trucking company to improve the transportation efficiency; comparison to analyze strategies to increase the cargo transportation efficiency of the trucking company when using routes of different types. Findings. The relationship between the organizational structure effectiveness of the production enterprise management and the probable problems in choosing the type of route for goods delivery to customers is defined. The authors proved that the efficiency of unitized cargo transportation depends on a well-defined strategy of increasing the road transport efficiency. Based on the conducted research the influence of economic and organizational factors on expediency of the decision concerning rational strategy of transportation efficiency maintenance is estimated. Three types of strategies are proposed, the content of which is reflected in the receipt of additional profit by the transport company from the production enterprise, when using pendulum routes by saving its resources (return of returnable packaging) and by finding cargo on the way back, as well as using delivery-assembling routes while minimizing fines for late goods delivery. The dependence visualization of the amount of the trucking company profit on the type of strategy adopted allows us to assess the prospects for the introduction of certain types of freight vehicles routes. Originality. Methodical approaches to ways substantiation of the trucking company profit increase, choosing their rational route according to the efficiency increase strategy of unitized cargo transportations from the manufacturer to clients have received further development. Practical value. The obtained results are aimed at improving the methodological approaches to optimizing the unitized cargo routes, based on the choice of two types of routes in certain conditions, the first is the pendulum route with simultaneous receipt of applications for goods delivery, the second – the delivery-assembling routes, taking into account fines for late delivery.

FLUCONAZOLE NANOGEL: FABRICATION AND IN VITRO EVALUATION FOR TOPICAL APPLICATION

Objective: The aim of this study is to develop and in vitro evaluation of prepared fluconazole nanogel for seborrheic dermatitis
 Methods: Fluconazole nanogel was formulated to act against seborrheic dermatitis. The fluconazole nanoparticles were prepared by a simplified evaporation method and evaluated for particle size, entrapment efficiency, and percent in vitro drug release. The nanogel was also characterized based on parameters like particle size, percent entrapment efficiency, shape surface morphology, rheological properties, in vitro release R² = 0.9046, and release kinetics.
 Results: The nanoparticle with a combination of Eudragit RS and Tween 80 showed the best result with particle size in the range of 119.0 nm to 149.5 nm, with a cumulative percent drug release of 95 % up to 18 h. The formulated nanogel with optimum concentration of HPMC authenticate with particle size 149.50±0.5 with maximum drug release (92.13±0.32) %.
 Conclusion: Different percentages of polymers (ethyl-cellulose, eudragit, and tween 80) are used as variable components in the formulation of nanogel. The optimized batch showed good physical properties (flow index, spreadability, and viscosity) along with rapid drug release. Therefore, it can be concluded that nanogel containing fluconazole has potential application in topical delivery.

Abstract 307: Lymph node accumulation of theranostic lipid-based nanoparticles in healthy and diseased models: Preliminary results comparing nanoparticle morphology and targeting

Abstract Background: Accumulation of systemically administered nanoparticles (NPs) in lymph nodes has been exploited clinically for diagnostic imaging (e.g., USPIOs for lymph node metastasis) and therapeutic applications (e.g., vaccine delivery). However, the combination of diagnostic and therapeutic functionalities into a single theranostic NP has obliged undesirable trade-offs between either the imaging or drug delivery of the NP and their specific accumulation in lymph nodes. To overcome these trade-offs, we conducted a screen of various lipid-based theranostic NPs focusing on differing NP design and their resulting pharmacokinetic behaviours in healthy and diseased lymph node models. Methods: Lipid-based theranostic NPs with varying physicochemical characteristics (e.g., formulation, size and morphology, surface targeting, etc.) were prepared with positron emitting Cu-64 and administered systemically at equivalent NP doses in healthy and diseased rodent models (i.e., mice and rats). NP types were assessed for time-dependent accumulation in major lymph node basins via non-invasive whole-body PET/MR imaging at two or more timepoints per animal. 72-hours post-injection the animals were sacrificed, and lymph nodes and major organs were excised for gamma counting and pathological evaluation. Pharmacokinetic behaviour of NPs in healthy versus diseased lymph nodes were calculated in individual animals and in naïvely pooled datasets using non-compartmental analysis. Results: Preliminary analysis identified a leading NP candidate with specific lymph node targeting in healthy and diseased rodents: a discoidal, 35-nm peptide-targeted HDL-mimetic. In comparison with a spherical, 100-nm PEGylated NP, the discoidal NP obtained greater absolute (%ID) and relative (%ID/g) amounts of injected dose in anatomically matched lymph nodes than the spherical NP, regardless of lymph node pathology. At greatest measured concentration in healthy lymph nodes, typically 24-hpi, the differences between the discoidal and spherical NPs were on average 3-fold greater (2.893 vs. 0.864, %ID/g). Differences in other pharmacokinetic parameters such as AUC (%ID/g*h) and MRT (h) were equally pronounced. Conclusions: Our preliminary analysis uncovered a discoidal, peptide-targeted HDL-mimetic with remarkable accumulation in lymph nodes of healthy and diseased models. Future investigations will focus on the biochemical and cellular mechanisms underlying their unique lymphatic pharmacokinetics. These preliminary results provide key insights for design of theranostic NPs for non-invasive imaging and staging lymph node pathologies, and for applications in delivery of therapeutics to lymph nodes following systemic administration. Citation Format: Michael S. Valic, Mark Zheng, Lili Ding, Michelle Lai, Chris J. Zhang, Tina Ye, Jenny Ma, Michael Halim, Pamela Schimmer, Wenlei Jiang, Juan Chen, Gang Zheng. Lymph node accumulation of theranostic lipid-based nanoparticles in healthy and diseased models: Preliminary results comparing nanoparticle morphology and targeting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 307.

Abstract 1151: Targeting castration-resistant prostate cancer using mesenchymal stem cell exosomes for therapeutic microRNA let-7c delivery

Abstract Introduction: Castration-resistant prostate cancer (CRPC) has poor response to androgen deprivation therapy, which is caused by a sustained androgen receptor (AR) signal and therefore is considered as an incurable disease. MicroRNA let-7c has been implied as a tumor suppressor in prostate cancer by antagonizing AR expression and activity. In addition to cancer cells, our group previously also demonstrated that downregulation of let-7c by cancer-associated mesenchymal stem cells (MSCs) triggering a reactive stromal response to facilitate prostate cancer growth and metastasis (PLoS ONE 8(8): e71637). Accordingly, treatment with exogenous let-7c would target both cancer cells and their associated MSCs and could be an attractive therapeutic approach to effectively inhibit CRPC recurrence and prevent metastasis. Exosomes are nanometer-sized membrane-bound vesicles with functions as mediators of cell-cell communication, which have the absolute predominance in biocompatibility for clinical applications in drug delivery and gene therapy. Objective: By taking the intrinsic tumor-targeting property of MSCs, this study aimed to investigate the feasibility of using MSC-derived exosomes as an exogenous let-7c delivery system to target CRPC. Methods: Relative miRNA-let-7c expression across various prostate cancer cell lines was examined using q-RT PCR. MSC-derived exosomes were collected from a 3A6 human bone marrow-derived MSC cell line after cell transfection with pre-miR negative control and pre-miR-let-7c, and further characterized through transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot. The effects of either naked or MSC-exosome encapsulated let-7c on CRPC cells was determined by WST-1 cell proliferation assay and wound healing migration assay. Results: MiRNA-let-7c expression was confirmed to be downregulated in most of CRPC-like cell lines compared with androgen-sensitive LNCaP. Overexpression of pre-miR-let-7 inhibited the ability of cell proliferation and migration of prostate cancer cells. Exogenous microRNAs can be successfully packaged into MSC-exosomes by cell transfection, without a disruption of exosome integrity. Treatment of CRPC-like PC3 (AR-negative) and CWR22r-v1 (AR-positive) cells with MSC-exosome encapsulated let-7c effectively delivered let-7c into cells and resulted in a significant reduction in cancer cell growth and metastasis in vitro. Conclusion: Herein, we have provided in vitro evidences to prove the concept that microRNA let-7c is a potential therapeutic intervention for CRPC, as well as MSC-derived exosomes can serve as a therapeutic let-7c delivery system to target the CRPC. Further in vivo validation of distribution and therapeutic efficacy of MSC-exosome-delivered let-7c in CRPC xenograft mouse model is currently being explored. Citation Format: Ida Kurniawati, Chia-Yen Hsueh, Shian-Ying Sung, Chia-Ling Hsieh. Targeting castration-resistant prostate cancer using mesenchymal stem cell exosomes for therapeutic microRNA let-7c delivery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1151.

The in vitro release features of 5-Fluorouracil from tablets with chitosan, soy protein extract and chitosan-soyprotein extract blend as carriers and their thermal degradation characteristics

Natural polymers are finding widespread applications in drug delivery, scaffold fabrication, bio plastic production, food packaging, wound dressing etc. due to their availability, biodegradability, biocompatibility, renewable nature, ease of modification to achieve the desirable properties etc. In the present study, the commercially available soy protein extract (SPE), chitosan(CSN) and their physical blend(CSN-SPE) have been chosen as drug carrier matrices to campare their in vitro drug release features in simulated intestinal fluid for controlled release applications taking 5-fluorouracil (5-FU) as a typical drug. The percentages of 5-FU released from the SPE, CSN and CSN-SPE tablets as a function of time were quantified by reverse phase High Performance Liquid Chromatography using KH2PO4 solution (pH 6.8) as the mobile phase and C-18 column as the stationery phase. The observed drug release features were found to be different for these polymer carriers. The percentages of drug released during the initial periods upto 60 min were less in the CSN-SPE tablet than those observed for CSN and SPE tablets. This implied that the drug release rate can be modified by the proper choice of natural polymers in the blends as carriers. The thermal degradation characteristics of CSN, SPE and CSN-SPE blend and their 5-FU tablets were also analysed by simultaneous Thermogravimetry (TG) and Differential Thermal Analysis (DTA). Comparative analysis of the TG and DTA traces of these polymers and their 5-FU tablets implied that there may be a drug-matrix interaction. This along with different degrees of swellability and degradability of these polymers might account for the differences in the drug release features. The structures of CSN, SPE and CSN-SPE blend were characterized by FT-IR spectroscopy.

Oxidized Alginate Dopamine Conjugate: In Vitro Characterization for Nose-to-Brain Delivery Application.

Background: The blood–brain barrier (BBB) bypass of dopamine (DA) is still a challenge for supplying it to the neurons of Substantia Nigra mainly affected by Parkinson disease. DA prodrugs have been studied to cross the BBB, overcoming the limitations of DA hydrophilicity. Therefore, the aim of this work is the synthesis and preliminary characterization of an oxidized alginate-dopamine (AlgOX-DA) conjugate conceived for DA nose-to-brain delivery. Methods: A Schiff base was designed to connect oxidized polymeric backbone to DA and both AlgOX and AlgOX-DA were characterized in terms of Raman, XPS, FT-IR, and 1H- NMR spectroscopies, as well as in vitro mucoadhesive and release tests. Results: Data demonstrated that AlgOX-DA was the most mucoadhesive material among the tested ones and it released the neurotransmitter in simulated nasal fluid and in low amounts in phosphate buffer saline. Results also demonstrated the capability of scanning near-field optical microscopy to study the structural and fluorescence properties of AlgOX, fluorescently labeled with fluorescein isothiocyanate microstructures. Interestingly, in SH-SY5Y neuroblastoma cell line up to 100 μg/mL, no toxic effect was derived from AlgOX and AlgOX-DA in 24 h. Conclusions: Overall, the in vitro performances of AlgOX and AlgOX-DA conjugates seem to encourage further ex vivo and in vivo studies in view of nose-to-brain administration.

Application of Thermoresponsive IntrinsicallyDisordered Protein Polymers in Nanostructured and Microstructured Materials.

Modulation of inter- and intramolecular interactions between bioinspired designer molecules can be harnessed for developing functional structures that mimic the complex hierarchical organization of multicomponent assemblies observed in nature. Furthermore, such multistimuli-responsive molecules offer orthogonal tunability for generating versatile multifunctional platforms via independent biochemical and biophysical cues. In this review, the remarkable physicochemical and mechanical properties of genetically engineered protein polymers derived from intrinsically disordered proteins, specifically elastin and resilin, are discussed. This review highlights emerging technologies which use them as building blocks in the fabrication of highly programmable structured biomaterials for applications in delivery of biotherapeutic cargo and regenerative medicine.

Using molecular dynamics simulations to prioritize and understand AI-generated cell penetrating peptides

Cell-penetrating peptides have important therapeutic applications in drug delivery, but the variety of known cell-penetrating peptides is still limited. With a promise to accelerate peptide development, artificial intelligence (AI) techniques including deep generative models are currently in spotlight. Scientists, however, are often overwhelmed by an excessive number of unannotated sequences generated by AI and find it difficult to obtain insights to prioritize them for experimental validation. To avoid this pitfall, we leverage molecular dynamics (MD) simulations to obtain mechanistic information to prioritize and understand AI-generated peptides. A mechanistic score of permeability is computed from five steered MD simulations starting from different initial structures predicted by homology modelling. To compensate for variability of predicted structures, the score is computed with sample variance penalization so that a peptide with consistent behaviour is highly evaluated. Our computational pipeline involving deep learning, homology modelling, MD simulations and synthesizability assessment generated 24 novel peptide sequences. The top-scoring peptide showed a consistent pattern of conformational change in all simulations regardless of initial structures. As a result of wet-lab-experiments, our peptide showed better permeability and weaker toxicity in comparison to a clinically used peptide, TAT. Our result demonstrates how MD simulations can support de novo peptide design by providing mechanistic information supplementing statistical inference.

Delivery of antimicrobial peptides to model membranes by cubosome nanocarriers

Antimicrobial peptides (AMPs), which typically disrupt the bacterial wall prompting leakage or lysis of the cell, form a growing contingent in the arsenal against antibiotic resistant bacteria. The effectiveness of AMPs is, however, hampered by their low solubility, general chemical and physical instability, and short half-life in vivo. Lipid nanocarriers such as cubosomes are effective at encapsulating and protecting proteins while simultaneously showing promise in delivery applications. Here, the efficacy of cubosome mediated delivery of AMPs is evaluated by the in-situ surface characterization of model membranes with varying composition. The cubosomes were observed to initially fuse with the membranes, with subsequent membrane disruption observed after approximately 20 – 60 min. The time for the disruption was sensitive to the charge of the cubosome as well as the composition of the bilayer. More physiologically relevant bilayers including lipids with phospho-(1′-rac-glycerol) (PG) or phosphoethanolamine (PE) headgroups were more vulnerable than those of neat phosphocholine (PC). Notably, disruption to the bilayer occurred an order of magnitude faster for encapsulated AMP compared to free AMP.

Solving Last-Mile Deliveries for Dairy Products Using a Biased Randomization-Based Spreadsheet. A Case Study

During recent years, Last-mile deliveries (LMD) have become relevant due to its application in e-commerce, urban logistics, and food delivery among others. This work addresses an LMD denoted as a Vehicle Routing Problem with time windows (VRPTW) and aims to minimize total time of the distribution process (i.e., makespan). The LMD is an NP-Hard problem that refers to the delivery of goods from a consolidation center to a destination. For solving the problem, a spreadsheet-based solution that employs a multi-start algorithm based on the biased-randomized version of the nearest neighbor heuristic is introduced. Real historical data of last-mile deliveries for dairy products in Bogotá (Colombia) was considered for evaluating our proposed method. Computational experiments are carried out to show the competitiveness of our method in terms of makespan, number of vehicles, average vehicle occupancy, average load and costs. Some insights for future works are also provided.

Cellular Uptake of Mildly Oxidized Nano-Graphene for Drug- Delivery Applications

Cellular Uptake of Mildly Oxidized Nano-Graphene for Drug- Delivery Applications

Observation of strong excitonic magneto-chiral anisotropy in twisted bilayer van der Waals crystals

The interplay between chirality and magnetism generates a distinct physical process, the magneto-chiral effect, which enables one to develop functionalities that cannot be achieved solely by any of the two. Such a process is universal with the breaking of parity-inversion and time-reversal symmetry simultaneously. However, the magneto-chiral effect observed so far is weak when the matter responds to photons, electrons, or phonons. Here we report the first observation of strong magneto-chiral response to excitons in a twisted bilayer tungsten disulfide with the amplitude of excitonic magneto-chiral (ExMCh) anisotropy reaches a value of ~4%. We further found the ExMCh anisotropy features with a spectral splitting of ~7 nm, precisely the full-width at half maximum of the excitonic chirality spectrum. Without an externally applied strong magnetic field, the observed ExMCh effect with a spontaneous magnetic moment from the ferromagnetic substrate of thulium iron garnet at room temperature is favorable for device applications. The unique ExMCh processes provide a new pathway to actively control magneto-chiral applications in photochemical reactions, asymmetric synthesis, and drug delivery.

Adsorption of Polymer-Grafted Nanoparticles on Curved Surfaces

Nanometer-curved surfaces are abundant in biological systems as well as in nano-sized technologies. Properly functionalized polymer-grafted nanoparticles (PGNs) adhere to surfaces with different geometries and curvatures. This work explores some of the energetic and mechanical characteristics of the adhesion of PGNs to surfaces with positive, negative and zero curvatures using Coarse-Grained Molecular Dynamics (CGMD) simulations. Our calculated free energies of binding of the PGN to the curved and flat surfaces as a function of separation distance show that curvature of the surface critically impacts the adhesion strength. We find that the flat surface is the most adhesive, and the concave surface is the least adhesive surface. This somewhat counterintuitive finding suggests that while a bare nanoparticle is more likely to adhere to a positively curved surface than a flat surface, grafting polymer chains to the nanoparticle surface inverts this behavior. Moreover, we studied the rheological behavior of PGN upon separation from the flat and curved surfaces under external pulling force. The results presented herein can be exploited in drug delivery and self-assembly applications.

Design and Development of Hybrid Hydrogels for Biomedical Applications: Recent Trends in Anticancer Drug Delivery and Tissue Engineering.

The applications of hydrogels in biomedical field has been since multiple decades. Discoveries in biology and chemistry render this platform endowed with much engineering potentials and growing continuously. Novel approaches in constructing these materials have led to the production of complex hybrid hydrogels systems that can incorporate both natural and synthetic polymers and other functional moieties for mediated cell response, tunable release kinetic profiles, thus they are used and research for diverse biomedical applications. Recent advancement in this field has established promising techniques for the development of biorelevant materials for construction of hybrid hydrogels with potential applications in the delivery of cancer therapeutics, drug discovery, and re-generative medicines. In this review, recent trends in advanced hybrid hydrogels systems incorporating nano/microstructures, their synthesis, and their potential applications in tissue engineering and anticancer drug delivery has been discussed. Examples of some new approaches including click reactions implementation, 3D printing, and photopatterning for the development of these materials has been briefly discussed. In addition, the application of biomolecules and motifs for desired outcomes, and tailoring of their transport and kinetic behavior for achieving desired outcomes in hybrid nanogels has also been reviewed.

Mechanism of Mesoporous Silica Nanoparticle Interaction with Hairy Root Cultures during Nanoharvesting of Biomolecules.

Cellular uptake and expulsion mechanisms of engineered mesoporous silica nanoparticles (MSNPs) are important in their design for novel biomolecule isolation and delivery applications such as nanoharvesting, defined as using nanocarriers to transport and isolate valuable therapeutics (secondary metabolites) out of living plant organ cultures (e.g., hairy roots). Here, temperature-dependent MSNP uptake and recovery processes in hairy roots are examined as a function of surface chemistry. MSNP uptake into hairy roots and time-dependent expulsion are quantified using Ti content (present for biomolecule binding) and fluorescence spectroscopy of fluorescently tagged MSNPs, respectively. The results suggest that functionalization and surface charge (regulated by amine group attachment) play the biggest role in the effectiveness of uptake and recovery. Comparison of MSNP interactions with hairy roots at 4 and 23°C shows that weakly charged MSNPs functionalized only with Ti are taken up and expelled by thermally activated mechanisms, while amine-modified positively charged particles are taken up and expelled mainly by direct penetration of cell walls. Amine-functionalized MSNPs move spontaneously in and out of plant cells by dynamic exchange with a residence time of 20 ± 5min, suggesting promise as a biomolecule nanoharvesting platform for plant organ cultures.