Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology

Hydrophilic polymers are the center of research emphasis in nanotechnology because of their perceived “intelligence”. They can be used as thin films, scaffolds, or nanoparticles in a wide range of biomedical and biological applications. Here we highlight recent developments in engineering uncrosslinked and crosslinked hydrophilic polymers for these applications. Natural, biohybrid, and synthetic hydrophilic polymers and hydrogels are analyzed and their thermodynamic responses are discussed. In addition, examples of the use of hydrogels for various therapeutic applications are given. We show how such systems' intelligent behavior can be used in sensors, microarrays, and imaging. Finally, we outline challenges for the future in integrating hydrogels into biomedical applications.     

Chitosan: A Unique Polysaccharide for Drug Delivery

Abstract

The aim of this review is to give an insight into the many potential applications of chitosan as a pharmaceutical drug carrier. The first part of this review concerns the principal uses of chitosan as an excipient in oral formulations (particularly as a direct tableting agent) and as a vehicle for parenteral drug delivery devices. The use of chitosan to manufacture sustained-release systems deliverable by other routes (nasal, ophthalmic, transdermal, and implantable devices) is discussed in the second part.     

Nanoindentation of viscoelastic solids: A critical assessment of experimental methods

The viscoelastic functions measured by nanoindentation (or atomic force microscopy), are coupled in complex ways to the measurement system’s time constants, phase shifts created by the instrument’s electronics, the actuator’s dynamics, the instrument’s load frame stiffness and requisite modeling assumptions. The ways in which these factors potentially affect the load, displacement, phase angle, stiffness and damping data are discussed in the context of nanoindentation experiments performed in the time and frequency domains. By drawing attention to these potential sources of experimental error, the objective is to motivate experimental verification in a manner that will enhance accuracy and, thus, enable future breakthroughs in the application of nanoindentation to viscoelastic solids.     

In situ forming implants for the delivery of metronidazole to periodontal pockets: formulation and drug release studies

This study was performed to obtain prolonged drug release with biodegradable in situ forming implants for the local delivery of metronidazole to periodontal pockets. The effect of polymer type (capped and uncapped PLGA), solvent type (water-miscible and water-immiscible) and the polymer/drug ratio on in vitro drug release studies were investigated. In situ implants with sustained metronidazole release and low initial burst consisted of capped PLGA and N-methyl-2-pyrolidone as solvent. Mucoadhesive polymers were incorporated into the in situ implants in order to modify the properties of the delivery systems towards longer residence times in vivo. Addition of the polymers changed the adhesiveness and increased the viscosity and drug release of the formulations. However, sustained drug release over 10 days was achievable. Biodegradable in situ forming implants are therefore an attractive delivery system to achieve prolonged release of metronidazole at periodontal therapy.     

Biological Containers: Protein Cages as Multifunctional Nanoplatforms

Materials scientists increasingly draw inspiration from the study of how biological systems fabricate materials under mild synthetic conditions by using self‐assembled macromolecular templates. Containerlike protein architectures such as viral capsids and ferritin are examples of such biological templates. These protein cages have three distinct interfaces that can be synthetically exploited: the interior, the exterior, and the interface between subunits. The subunits that comprise the building blocks of these structures can be modified both chemically and genetically in order to impart designed functionality to different surfaces of the cage. Therefore, the cages possess a great deal of synthetic flexibility, which allows for the introduction of multifunctionality in a single cage. In addition, hierarchical assembly of the functionalized cages paves the way for development of a new class of materials with a wide range of applications from electronics to biomedicine.     

Monoolein: A Review of the Pharmaceutical Applications

Earlies studies suggest that solution calorimetry can be used to determine the extent of amorphous content of drug and excipient, when the solubility and dissolution rate of the compound in the chosen solvent are reasonably high. In the present study, the use of solution calorimetry for assessment of amorphous content of a sample that is not completely dissolved in a solvent was evaluated. Physical mixtures of lactose and spray‐dried lactose samples were analysed. The amorphous content of the physical mixtures and the spray‐dried samples varied from 0% to 100% determined by isothermal microcalorimetry. The enthalpy of solution (Δ_solH) was determined in water. The lactose samples were dissolved quickly in water. In addition, the enthalpy accompanied with an addition of a lactose sample in an over saturated aqueous solution (Δ_satH) (prepared from the corresponding lactose sample) was determined. The lactose sample did not completely dissolve in the over saturated aqueous solution. An excellent correlation was observed between Δ_solH and the amorphous content of the samples. Interestingly, there was a linear correlation also between Δ_satH and the amorphous content of the samples. Further, a linear relationship was observed between the Δ_satH and the Δ_solH of the samples. Therefore, solution calorimetry may represent a rapid and simple method for determining the amorphous content also in samples that are not completely dissolved in the solvent.     

In situ gelling formulation based on methylcellulose/pectin system for oral-sustained drug delivery to dysphagic patients

Background: Oral-sustained release gel formulations with suitable rheological properties have been proposed as a means of improving the compliance of dysphagic and geriatric patients who have difficulties with handling and swallowing oral dosage forms. Aim: We have modified the rheological and release properties of thermally reversible methylcellulose solutions by admixture with pectin, the gelation of which is ion-responsive, with the aim of formulating an in situ gelling vehicle suitable for oral-sustained drug delivery. Method: Gels formed by solutions containing methylcellulose (1.0–2.0%) and pectin (0.5–2.0%) were assessed for suitable gel strength, and in vitro and in vivo release of paracetamol. Results: Addition of 1.5% pectin to a 2.0% methylcellulose formulation containing 20% d-sorbitol and calcium ions in complexed form increased the gel strength and provided a formulation with a suitable viscosity for ease of swallowing by dysphagic patients. Gels formed in situ after oral administration of this formulation retained their integrity in the rat stomach for sufficient time for sustained release to be achieved. In vitro release of paracetamol from methylcellulose, pectin, and methylcellulose/pectin gels was diffusion-controlled. Plasma levels of paracetamol after oral administration to rats (gastric pH 2.6 and 5.5) of a solution including 2.0% methylcellulose/1.5% pectin showed improved sustained release compared with that from both 2.0% methylcellulose and 1.5% pectin solutions. Conclusions: The addition of suitable concentrations of pectin to methylcellulose solutions produces in situ gelling formulations with suitable viscosity for administration to dysphagic patients and improved sustained release characteristics.     

Flash technology-based self-assembly in nanoformulation: Fabrication to biomedical applications

Advances in nanoformulation have driven progress in biomedicine by producing nanoscale tools for biosensing, imaging, and drug delivery. Flash-based technology, the combination of rapid mixing technique with the self-assembly of macromolecules, is a new engine for the translational nanomedicine. Here, we review the state-of-the-art in flash-based self-assembly including theoretical and experimental principles, mixing device design, and applications. We highlight the fields of flash nanocomplexation (FNC) and flash nanoprecipitation (FNP), with an emphasis on biomedical applications of FNC, and discuss challenges and future directions for flash-based nanoformulation in biomedicine.     

A novel vehicle for local protein delivery to the inner ear: injectable and biodegradable thermosensitive hydrogel loaded with PLGA nanoparticles

Delivery of biomacromolecular drugs into the inner ear is challenging, mainly because of their inherent instability as well as physiological and anatomical barriers. Therefore, protein-friendly, hydrogel-based delivery systems following local administration are being developed for inner ear therapy. Herein, biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing interferon α-2?b (IFN α-2?b) were loaded in chitosan/glycerophosphate (CS/GP)-based thermosensitive hydrogel for IFN delivery by intratympanic injection. The injectable hydrogel possessed a physiological pH and formed semi-solid gel at 37?°C, with good swelling and deswelling properties. The CS/GP hydrogel could slowly degrade as visualized by scanning electron microscopy (SEM). The presence of NPs in CS/GP gel largely influenced in vitro drug release. In the guinea pig cochlea, a 1.5- to 3-fold increase in the drug exposure time of NPs-CS/GP was found than those of the solution, NPs and IFN-loaded hydrogel. Most importantly, a prolonged residence time was attained without obvious histological changes in the inner ear. This biodegradable, injectable, and thermosensitive NPs-CS/GP system may allow longer delivery of protein drugs to the inner ear, thus may be a potential novel vehicle for inner ear therapy.     

Carbon nanotubes in biology and medicine: In vitro and in vivo detection, imaging and drug delivery

Carbon nanotubes exhibit many unique intrinsic physical and chemical properties and have been intensively explored for biological and biomedical applications in the past few years. In this comprehensive review, we summarize the main results from our and other groups in this field and clarify that surface functionalization is critical to the behavior of carbon nanotubes in biological systems. Ultrasensitive detection of biological species with carbon nanotubes can be realized after surface passivation to inhibit the non-specific binding of biomolecules on the hydrophobic nanotube surface. Electrical nanosensors based on nanotubes provide a label-free approach to biological detection. Surface-enhanced Raman spectroscopy of carbon nanotubes opens up a method of protein microarray with detection sensitivity down to 1 fmol/L. In vitro and in vivo toxicity studies reveal that highly water soluble and serum stable nanotubes are biocompatible, nontoxic, and potentially useful for biomedical applications. In vivo biodistributions vary with the functionalization and possibly also size of nanotubes, with a tendency to accumulate in the reticuloendothelial system (RES), including the liver and spleen, after intravenous administration. If well functionalized, nanotubes may be excreted mainly through the biliary pathway in feces. Carbon nanotube-based drug delivery has shown promise in various In vitro and in vivo experiments including delivery of small interfering RNA (siRNA), paclitaxel and doxorubicin. Moreover, single-walled carbon nanotubes with various interesting intrinsic optical properties have been used as novel photoluminescence, Raman, and photoacoustic contrast agents for imaging of cells and animals. Further multidisciplinary explorations in this field may bring new opportunities in the realm of biomedicine.      

A Bayesian approach to gross error detection in chemical process data: Part II: Simulation results

Tamhane, A.C., Iordache, C. and Mah, R.S.H., 1988. A Bayesian approach to gross error detection in chemical process data. Part II: Simulation results. Chemometrics and Intelligent Laboratory Systems, 4: 131–146.The performance of the gross error detection scheme based on the Bayesian test is evaluated using Monte Carlo simulation methods. Effects of selected control factors (implementation options) and noise factors (e.g., violation of assumptions and misspecification of priors) are studied. A comparison is made with the gross error detection scheme based on the non-Bayesian measurement test of Mah and Tamhane. The Bayesian scheme is found to be relatively robust. It performs better than the measurement test scheme when gross error occurrences are not infrequent. However, its performance characteristics converge rather slowly and hence accurate prior estimates of the various unknown parameters are necessary before the method can be put to practical use.In conclusion, the Bayesian approach offers the promise of improving gross error detection and identification capabilities by using past failure data. Its technical feasibility is demonstrated by this investigation, but much remains to be done to make it a practical method.     

Local drug delivery system for the treatment of osteomyelitis: In vitro evaluation

Local antimicrobial delivery is a potential area of research conceptualized to provide alternative and better methods of treatment for cases, as osteomyelitis where avascular zones prevent the delivery of drugs from conventional routes of administration. Drug-loaded polymers and calcium phosphates as hydroxyapatites have been tried earlier. Bioactive glasses are bone-filling materials used for space management in orthopedic and dental surgery. A new bioactive glass (SSS2) was synthesized and fabricated into porous scaffold with a view to provide prolonged local delivery of gatifloxacin and fluconazole as suitable for the treatment of osteomyelitis. The new SSS2 was characterized by Fourier transform infrared (FTIR) and X-ray diffraction (XRD) analyses. In addition, the bioactivity of the SSS2 glass and resulting scaffold was examined by in vitro acellular method and ascertained by FTIR and XRD. The pore size distribution was analysed by mercury intrusion porosimetry and the release of drugs from scaffolds were studied in vitro. The glass and the resulting scaffolds were bioactive indicating that they can bond with bone in vivo. The scaffolds were porous with pores predominantly in the range of 10–60 µm, released the drugs effectively for 6 weeks and deemed suitable for local delivery of drugs to treat osteomyelitis.     

A new approach to production regularity assessment in the oil and chemical industries

This article presents a new approach to production regularity assessment in the oil and chemical industries. The production regularity is measured by the throughput capacity distribution. A brief survey of some existing techniques is presented, and the structure of the new approach is introduced. The proposed approach is based on analytical methods, i.e. no simulation is necessary. The system modeling is split into three levels: components, basic subsystems, and merged subsystems, and two modeling methods are utilized: Markov modeling and a rule-based method. The main features of the approach are as follows: (1) short calculation time; (2) systems of dependent components can be modeled; (3) maintenance strategies can be modeled; and (4) a variety of system configurations can be modeled. A simple case study is used to demonstrate how the proposed approach can be applied.     

From scattered sources to comprehensive technology landscape : A recommendation-based retrieval approach

Mapping the technology landscape is crucial for market actors to take informed investment decisions. However, given the large amount of data on the Web and its subsequent information overload, manually retrieving information is a seemingly ineffective and incomplete approach. In this work, we propose an end-to-end recommendation based retrieval approach to support automatic retrieval of technologies and their associated companies from raw Web data. This is a two-task setup involving (i) technology classification of entities extracted from company corpus, and (ii) technology and company retrieval based on classified technologies. Our proposed framework approaches the first task by leveraging DistilBERT which is a state-of-the-art language model. For the retrieval task, we introduce a recommendation-based retrieval technique to simultaneously support retrieving related companies, technologies related to a specific company and companies relevant to a technology. To evaluate these tasks, we also construct a data set that includes company documents and entities extracted from these documents together with company categories and technology labels. Experiments show that our approach is able to return 4 times more relevant companies while outperforming traditional retrieval baseline in retrieving technologies.     

A rule-based multi-criteria approach to inventory classification

The traditional inventory classification method classifies stock keeping units (SKUs) to three classes based on their annual dollar usage, while in real world problems, other criteria are important as well. In this paper, considering multi-criteria situations, a simple, effective and practical rule-based method is designed and implemented in a real world case, using MATLAB software. The most important characteristic of the proposed method is taking into account the inherent ambiguities that exist in the reasoning process of the system of classification. The methodology and the method proposed here may be easily implemented by inventory managers. The results obtained from the case study in this paper are compared with the analytic hierarchy process (AHP) method. Finally concluding remarks and suggestions for future work are provided.     

A disaggregate approach to crash rate analysis

This paper presents a disaggregate approach to crash rate analysis. Enumerating crash rates on a per trip-kilometer basis, the proposed method removes the linearity assumption inherent in the conventional quotient indicator of accidents per unit travel distance. The approach involves combining two disparate datasets on a geographic information systems (GIS) platform by matching accident records to a defined travel corridor. As an illustration of the methodology, travel information from the Victorian Activity and Travel Survey (VATS) and accident records contained in CrashStat were used to estimate the crash rates of Melbourne residents in different age-sex groups according to time of the day and day of the week. The results show a polynomial function of a cubic order when crash rates are plotted against age group, which contrasts distinctly with the U-shape curve generated by using the conventional aggregate quotient approach. Owing to the validity of the many assumptions adopted in the computation, this study does not claim that the results obtained are conclusive. The methodology, however, is seen as providing a framework upon which future crash risk measures could be based as the use of spatial tracking devises become prevalent in travel surveys.     

Ciprofloxacin Liposomes as Vesicular Reservoirs for Ocular Delivery: Formulation,Optimization, and In Vitro Characterization

Management of extraocular diseases is mainly limited by the inability to provide long-term drug delivery without avoiding the systemic drug exposure and/or affecting the intraocular structures and poor availability of drugs, which may be overcome by prolonging the contact time with the ocular system, for instance with liposomes. Development and optimization of reverse phase evaporation ciprofloxacin (CPF) HCl liposomes for ocular drug delivery was carried out using a 2⁵ full factorial design based on five independent variables. The effects of the studied parameters on drug entrapment efficiency (EE), particle size, and percentage of drug released after 1 and 10 h were investigated. The results obtained pointed out that the molar concentration of cholesterol was the predominant factor that increased the EE% of the drug and the particle size responses. The percentage of drug released after 1 h was significantly controlled by the initial CPF concentration while that after 10 h was controlled by molar cholesterol concentration. The designed liposomes had average particle sizes that ranged from 2.5 to 7.23 μm. In addition, liposomes revealed a fast release during the first hour followed by a more gradual drug release during the 24-h period according to Higuchi diffusion model.