PEI-based functional materials: Fabrication techniques, properties, and biomedical applications.

Cationic polymers have recently attracted considerable interest as research breakthroughs for various industrial and biomedical applications. They are particularly interesting due to their highly positive charges, acceptable physicochemical properties, and ability to undergo further modifications, making them attractive candidates for biomedical applications. Polyethyleneimines (PEIs), as the most extensively utilized polymers, are one of the valuable and prominent classes of polycations. Owing to their flexible polymeric chains, broad molecular weight (MW) distribution, and repetitive structural units, their customization for functional composites is more feasible. The specific beneficial attributes of PEIs could be introduced by purposeful functionalization or modification, long service life, biocompatibility, and distinct geometry. Therefore, PEIs have significant potential in biotechnology, medicine, and bioscience. In this review, we present the advances in PEI-based nanomaterials, their transfection efficiency, and their toxicity over the past few years. Furthermore, the potential and suitability of PEIs for various applications are highlighted and discussed in detail. This review aims to inspire readers to investigate innovative approaches for the design and development of next-generation PEI-based nanomaterials possessing cutting-edge functionalities and appealing characteristics.

Bioinspired Polymers: Transformative Applications in Biomedicine and Regenerative Medicine.

Bioinspired polymers have emerged as a promising field in biomaterials research, offering innovative solutions for various applications in biomedical engineering. This manuscript provides an overview of the advancements and potential of bioinspired polymers in tissue engineering, regenerative medicine, and biomedicine. The manuscript discusses their role in enhancing mechanical properties, mimicking the extracellular matrix, incorporating hydrophobic particles for self-healing abilities, and improving stability. Additionally, it explores their applications in antibacterial properties, optical and sensing applications, cancer therapy, and wound healing. The manuscript emphasizes the significance of bioinspired polymers in expanding biomedical applications, addressing healthcare challenges, and improving outcomes. By highlighting these achievements, this manuscript highlights the transformative impact of bioinspired polymers in biomedical engineering and sets the stage for further research and development in the field.

Cryogels: Advancing Biomaterials for Transformative Biomedical Applications.

Cryogels, composed of synthetic and natural materials, have emerged as versatile biomaterials with applications in tissue engineering, controlled drug delivery, regenerative medicine, and therapeutics. However, optimizing cryogel properties, such as mechanical strength and release profiles, remains challenging. To advance the field, researchers are exploring advanced manufacturing techniques, biomimetic design, and addressing long-term stability. Combination therapies and drug delivery systems using cryogels show promise. In vivo evaluation and clinical trials are crucial for safety and efficacy. Overcoming practical challenges, including scalability, structural integrity, mass transfer constraints, biocompatibility, seamless integration, and cost-effectiveness, is essential. By addressing these challenges, cryogels can transform biomedical applications with innovative biomaterials.

Nanosystems in Cardiovascular Medicine: Advancements, Applications, and Future Perspectives.

Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality globally. Despite significant advancements in the development of pharmacological therapies, the challenges of targeted drug delivery to the cardiovascular system persist. Innovative drug-delivery systems have been developed to address these challenges and improve therapeutic outcomes in CVDs. This comprehensive review examines various drug delivery strategies and their efficacy in addressing CVDs. Polymeric nanoparticles, liposomes, microparticles, and dendrimers are among the drug-delivery systems investigated in preclinical and clinical studies. Specific strategies for targeted drug delivery, such as magnetic nanoparticles and porous stent surfaces, are also discussed. This review highlights the potential of innovative drug-delivery systems as effective strategies for the treatment of CVDs.

Functional properties of thermally tampered poly(ethylene oxide).

Introduction: Poly(ethylene oxide) (PEO) is the most common polymer used in commercial abuse-deterrent tablets. Due to its vulnerability to high-temperature manipulation, we investigated abuse-deterrent capability and the toxicity of this polymer upon thermal treatments at 80°C and 180°C for 1 hour. Methods: Tablets (200 mg PEO and 300 mg Avicel®) were directly compressed under 2000 lb. The thermally manipulated PEOs were evaluated for their viscosity, crushability, structural changes, and cell toxicity. Results: Our findings showed that 180°C-treated tablets underwent some degrees of oxidative degradation with profound toxicity in both mesenchymal stem cells and MG63 cells. The 180°C-treated tablets exhibited almost no resistance against crushing and were prone to abuse. While thermal processing of PEO at around its melting temperature is a common approach to enhance crush resistance of its dosage forms, thermal manipulation at close to the PEO's oxidation temperature can lead to structural changes, dramatic loss of crush and extraction resistance, and significant cell toxicity. Conclusion: Similar to the low molecular weight PEO, when thermally manipulated at its thermo-oxidative temperature, the high molecular weight PEO loses its deterrence performance and causes severe cell toxicity.

Applications of cryostructures in the chromatographic separation of biomacromolecules.

Macroporous-interconnected cryostructures are prepared via cryoprocess approaches, where polymerization, crosslinking-polymerization, or even chain aggregation is primarily conducted at the sub-freezing temperature of the medium followed by thawing. Given their unique desirable properties, cryostructures have been studied as a stationary phase in chromatography to purify and separate proteins. The macroporous cryostructures with their highly interconnected large (10-100 µm) pores have various advantages, including the high surface area, sponge-like morphology, high elasticity, low-pressure drop, short diffusion path, and a temporary residence. In this review, we elaborate on the methods used in the preparation of cryostructures and the factors affecting their properties. We also highlight the underlying progress in chromatography techniques that take advantage of cryostructures as stationary phases for separating multiple biomacromolecules.

Toxicity of the polymeric excipients in geriatric polypharmacy.

Geriatric polypharmacy is already a complicated issue in pharmacotherapy as multiple biological and pharmaceutical factors are involved. Given the fact that the geriatric population, in general, takes more than five medications for multiple diseases and most likely takes several supplements, there is a hidden issue with the types and amounts of the pharmaceutical inactive ingredients (polymers in particular) as they, as well as their impurities, may build up in an ill-performing body beyond their safety levels. In this commentary, we impart on biological factors, the importance of polymers, and the types and amounts of the impurities within each polymeric excipient that can potentially lead to severe pharmacological and biological impacts. Given the complex safety and toxicity issues in polypharmacy, we may need to revisit the safety standards and regulations on the inactive materials that are widely used in geriatric medications.

Opioid epidemic and the urge to discover new treatment options.

The primary tools to alleviate the opioid epidemic in the USA include strict Federal and State laws on opioid prescriptions, tracking opioid medications, accountability of the opioid manufacturers and physicians, as well as boosting public awareness. Although abuse-deterrent opioids have in part lowered the incidence of opioid abuse, many post-marketing studies are still pending and some products have been recalled or terminated. Moreover, some studies show that the current deterrent opioid products might potentially force the abusers to seek more-powerful and deadly illicit drugs that can lead to toxicity and hepatitis C infections. Along with all the positive developments, there remains a strong need to discover and develop nonaddictive opioids and comparable non-opioid alternatives for acute pain management.

Abuse-deterrent properties and cytotoxicity of poly(ethylene oxide) after thermal tampering.

Poly(ethylene oxide) (PEO) is the most common deterring agent used in the abuse-deterrent formulations (ADFs). In this study, we investigated the PEO's abuse-deterrent properties and its potential cytotoxicity after being heated at high temperatures (80 °C and 180 °C). The results indicated a significant loss in both crush and extraction resistance features of the polymer, which is primarily associated with the polymer degradation at the higher temperatures. The heat-treated PEO at the high temperature was also found to lose its controlled-release feature, upon which over 80% of the drug was released after one hour in the simulated gastric fluid. The cytotoxicity of the PEO was further assessed to evaluate the safety of the polymer following the thermal treatment. Our findings revealed a substantial loss in the viability of the cells exposed to the PEO treated at higher temperatures. Taken all, heating PEO at high temperatures can lead to a significant loss in both the crush/extraction resistance characteristics and the safety of the polymer. These findings reemphasize the fact that more appropriate and stricter test and regulations will be needed to assure that the abuse deterrent formulations are safe and effective under severe conditions of abuse.

Sustained delivery of olanzapine from sunflower oil-based polyol-urethane nanoparticles synthesised through a cyclic carbonate ring-opening reaction.

The forefront horizon of biomedical investigations in recent decades is parcelling-up and delivery of drugs to achieve controlled/targeted release. In this regard, developing green-based delivery systems for a spatiotemporal controlling therapeutic agent have drawn a lot of attention. A facile route based on cyclic carbonate ring-opening reaction has been utilised to synthesise a bio-based polyol-containing urethane bond [polyol-urethane (POU)] as a nanoparticulate drug delivery system of olanzapine in order to enhance its bioavailability. After characterisation, the nanoparticles were also estimated for in vitro release, toxicity, and pharmacokinetic studies. As olanzapine has shown poor bioavailability and permeability in the brain, the sustained release of olanzapine from the designed carriers could enhance pharmacokinetic effectiveness. POU in the aqueous solution formed micelles with a hydrophobic core and embedded olanzapine under the influence of its hydrophobic nature. Drug release from the nanoparticles (90 ± 0.43 nm in diameter) indicated a specific pattern with initial burst release, and then a sustained release behaviour (82 ± 3% after 168 h), by the Higuchi-based release mechanism. Pharmacokinetics assessments of POU-olanzapine nanoparticles were carried in male Wistar rats through intravenous administration. The obtained results paved a way to introduce the POU as an efficient platform to enhance the bioavailability of olanzapine in therapeutic methods.

Preparation of Mesalamine Nanoparticles Using a Novel Polyurethane- Chitosan Graft Copolymer.

BACKGROUND: Chitosan nanoparticle, a potential vehicle, is used as a hydrophilic carrier system since it can deliver drugs to specific sites and also control the drug release rate. Moreover, controlled release systems are designed to minimize systemic absorption and to achieve optimum delivery of the biologically active mesalamine to the distal small intestine and the colon. OBJECTIVE: The current study investigated the development of new nanoparticulate drug delivery systems based on polyurethane-chitosan copolymers. The copolymer shows good biodegradablity and biocompatiblity properties and thus can be considered as a potential carrier for drug delivery systems. METHOD: In this work, Polyurethane was obtained from the condensation reaction between polypropylene glycol (PPG) as prepolymerpolyol, 1, 4-butanediol (BD) as diol, dimethylol propionic acid (DMPA) as chain extender and also isophoronediisocyanate (IPDI). The synthesized polyurethane was grafted onto the prepared chitosan through a covalent binding and preparation of nanoparticles was done further through a coprecipitation process. The particle size of the prepared samples was evaluated with dynamic light scattering (DLS) technique. RESULTS: The obtained particle size of the samples was 80±0.05 nm. Characterization of the synthesized chitosan-polyurethane copolymer was performed by FT-IR spectroscopy, 13CNMR and 11HNMR spectroscopy. The morphology of the synthesized polyurethane-chitosan copolymers and the amount of the loaded drug were also examined using SEM images and UV-visible spectroscopy, respectively. Moreover, drug release behavior was examined in PBS (pH 7.4) at 37°C. It was concluded that the mesalamine release from polyurethane-chitosan was sustained and no initial burst release (burst effect) was observed and the percentage of mesalamine released from nanoparticles was 92.19±0.2% within 72 hrs. CONCLUSION: The results of the drug loaded nanoparticles showed that the drug loading process was performed successfully. As a result, polyurethane-chitosan copolymer can be a good candidate for drug delivery systems.

Design, characterization and in vitro evaluation of novel amphiphilic block sunflower oil-based polyol nanocarrier as a potential delivery system: Raloxifene-hydrochloride as a model.

Presently, modern pharmaceuticals, are almost exclusively derived from the arduous refining of petroleum whose supply is inherently unsustainable. In order to address this issue bio-based materials are increasingly being used for chemical synthesis, particularly in drug delivery systems. Biodegradable and biocompatible hyper-branched polyol (an alcohol containing three or more hydroxyl groups) was synthesized via a facile method through the ring-opening and thiol-ene click reactions at room temperature. Due to the bio-based content of the polyol backbone, the synthesized polyol had both excellent biodegradability and low cytotoxicity. Raloxifene hydrochloride, an oral selective estrogen receptor modulator, was used as a hydrophobic drug model to test the potential of polyol as a drug delivery system carrier. Polyol showed an amphiphilic character and could be prepared as a nanoparticle for the sustained delivery of raloxifene hydrochloride, a drug with poor bioavailability in aqueous solution. Raloxifene hydrochloride was readily encapsulated in the lipophilic core of polyol whose branched hydroxyls were on the external part of the prepared nanoparticles. The diameter of the nanoparticles was 94±0.43nm, their drug entrapment efficiency was 93±0.5% and they showed a sustained release profile (17±1.5% after 4weeks). The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay showed low toxicity towards human osteoblast MG-63 cells. Based on its good biodegradability and low cytotoxicity, polyol provides a bio-based source for the design new drug delivery systems.

Fully glutathione degradable waterborne polyurethane nanocarriers: Preparation, redox-sensitivity, and triggered intracellular drug release.

Polyurethanes are important class of biomaterials that are extensively used in medical devices. In spite of their easy synthesis, polyurethanes that are fully degradable in response to the intracellular reducing environment are less explored for controlled drug delivery. Herein, a novel glutathione degradable waterborne polyurethane (WPU) nanocarrier for redox triggered intracellular delivery of a model lipophilic anticancer drug, doxorubicin (DOX) is reported. The WPU was prepared from polyaddition reaction of isophorone diisocyanate (IPDI) and a novel linear polyester polyol involving disulfide linkage, disulfide labeled chain extender, dimethylolpropionic acid (DMPA) using dibutyltin dilaurate (DBTDL) as a catalyst. The resulting polyurethane self-assembles into nanocarrier in water. The dynamic light scattering (DLS) measurements and scanning electron microscope (SEM) revealed fast swelling and disruption of nanocarriers under an intracellular reduction-mimicking environment. The in vitro release studies showed that DOX was released in a controlled and redox-dependent manner. MTT assays showed that DOX-loaded WPU had a high in vitro antitumor activity in both HDF noncancer cells and MCF- 7 cancer cells. In addition, it is found that the blank WPU nanocarriers are nontoxic to HDF and MCF-7 cells even at a high concentration of 2mg/mL. Hence, nanocarriers based on disulfide labeled WPU have appeared as a new class of biocompatible and redox-degradable nanovehicle for efficient intracellular drug delivery.