Search

The effective treatment of various diseases requires not only medications but also precise delivery methods to the body and specific organs. In this regard, radiology plays a crucial role, acting as the eyes of physicians. In contrast, interventional radiology serves as its hands, acting as one of the most effective drug delivery systems. Among interventional radiology disciplines, arterial drug delivery through arteries holds paramount importance as organs primarily receive nourishment directly from them. Furthermore, regenerative medicine is a burgeoning field dedicated to repairing diverse body tissues without relying on pharmaceutical drugs. Stem cells, inherent in various parts of our bodies, are vital for tissue regeneration and reconstruction. Depending on the treatment approach, stem cells can be sourced from the patient's body (autologous) or another individual (allogeneic). There exist various types of stem cells across species, with regenerative properties observed in animals and even plants. However, targeted cell therapy is preferred over systematic injections throughout the body for better efficacy. This article aims to familiarize interventionalists with stem cells and provide them with a clear and helpful explanation of their functions, mechanisms of action, different sources, and other relevant aspects. This will help them select the most appropriate cells for their therapeutic purposes. By comprehensively understanding the significance of stem cells in interventional radiology, we can implement optimal methodologies to address diverse medical conditions efficiently.

Abstract Parasites, such as the malaria parasite P. falciparum, are critically dependent on host nutrients. Interference with nutrient uptake can lead to parasite death and, therefore, serve as a successful treatment strategy. P. falciparum parasites cannot synthesise cholesterol, and instead source this lipid from the host. Here, we tested whether cholesterol uptake pathways could be ‘hijacked’ for optimal drug delivery to the intracellular parasite. We found that fluorescent cholesterol analogues were delivered from the extracellular environment to the intracellular parasite. We investigated the uptake and inhibitory effects of conjugate compounds, where proven antimalarial drugs (primaquine and artesunate) were attached to steroids that mimic the structure of cholesterol. These conjugated antimalarial drugs improved the inhibitory effects against multiple parasite lifecycle stages, multiple parasite species, and drug-resistant parasites, whilst also lowering the toxicity to human host cells. Steroids with introduced peroxides also displayed antimalarial activity. These results provide a proof-of-concept that cholesterol mimics can be developed as a drug delivery system against apicomplexan parasites with the potential to improve drug efficacy, increase therapeutic index, and defeat drug resistance.

Abstract Extracellular vesicles (EVs) are nano-sized, membranous transporters of various active biomolecules with inflicting phenotypic capabilities, that are naturally secreted by almost all cells with a promising vantage point as a potential leading drug delivery platform. The intrinsic characteristics of their low toxicity, superior structural stability, and cargo loading capacity continue to fuel a multitude of research avenues dedicated to loading EVs with therapeutic and diagnostic cargos (pharmaceutical compounds, nucleic acids, proteins, and nanomaterials) in attempts to generate superior natural nanoscale delivery systems for clinical application in therapeutics. In addition to their well-known role in intercellular communication, EVs harbor microRNAs (miRNAs), which can alter the translational potential of receiving cells and thus act as important mediators in numerous biological and pathological processes. To leverage this potential, EVs can be structurally engineered to shuttle therapeutic miRNAs to diseased recipient cells as a potential targeted ‘treatment’ or ‘therapy’. Herein, this review focuses on the therapeutic potential of EV-coupled miRNAs; summarizing the biogenesis, contents, and function of EVs, as well as providing both a comprehensive discussion of current EV loading techniques and an update on miRNA-engineered EVs as a next-generation platform piloting benchtop studies to propel potential clinical translation on the forefront of nanomedicine.

The deposition of thin films plays a crucial role in surface engineering, tailoring structural modifications, and functionalization across diverse applications. Layer-by-layer self-assembly, a prominent thin-film deposition method, has witnessed substantial growth since its mid-20th-century inception, driven by the discovery of eligible materials and innovative assembly technologies. Of these materials, micro- and nanoscopic substrates have received far less interest than their macroscopic counterparts; however, this is changing. The catalogue of eligible materials, including nanoparticles, quantum dots, polymers, proteins, cells and liposomes, along with some well-established layer-by-layer technologies, have combined to unlock impactful applications in biomedicine, as well as other areas like food fortification, and water remediation. To access these fields, several well-established technologies have been used, including tangential flow filtration, fluidized bed, atomization, electrophoretic assembly, and dielectrophoresis. Despite the invention of these technologies, the field of particle layer-by-layer still requires further technological development to achieve a high-yield, automatable, and industrially ready process, a requirement for the diverse, reactionary field of biomedicine and high-throughput pharmaceutical industry. This review provides a background on layer-by-layer, focusing on how its constituent building blocks and bonding mechanisms enable unmatched versatility. The discussion then extends to established and recent technologies employed for coating micro- and nanoscopic matter, evaluating their drawbacks and advantages, and highlighting promising areas in microfluidic approaches, where one distinctly auspicious technology emerges, acoustofluidics. The review also explores the potential and demonstrated application of acoustofluidics in layer-by-layer technology, as well as analyzing existing acoustofluidic technologies beyond LbL coating in areas such as cell trapping, cell sorting, and multidimensional particle manipulation. Finally, the review concludes with future perspectives on layer-by-layer nanoparticle coating and the potential impact of integrating acoustofluidic methods. [ABSTRACT FROM AUTHOR]

The effective treatment of various diseases requires not only medications but also precise delivery methods to the body and specific organs. In this regard, radiology plays a crucial role, acting as the eyes of physicians. In contrast, interventional radiology serves as its hands, acting as one of the most effective drug delivery systems. Among interventional radiology disciplines, arterial drug delivery through arteries holds paramount importance as organs primarily receive nourishment directly from them. Furthermore, regenerative medicine is a burgeoning field dedicated to repairing diverse body tissues without relying on pharmaceutical drugs. Stem cells, inherent in various parts of our bodies, are vital for tissue regeneration and reconstruction. Depending on the treatment approach, stem cells can be sourced from the patient's body (autologous) or another individual (allogeneic). There exist various types of stem cells across species, with regenerative properties observed in animals and even plants. However, targeted cell therapy is preferred over systematic injections throughout the body for better efficacy. This article aims to familiarize interventionalists with stem cells and provide them with a clear and helpful explanation of their functions, mechanisms of action, different sources, and other relevant aspects. This will help them select the most appropriate cells for their therapeutic purposes. By comprehensively understanding the significance of stem cells in interventional radiology, we can implement optimal methodologies to address diverse medical conditions efficiently. [ABSTRACT FROM AUTHOR]

The recurrent nature of glioblastoma negatively impacts conventional treatment strategies leading to a growing need for nanomedicine. Nanotherapeutics, an approach designed to deliver drugs to specific sites, is experiencing rapid growth and gaining immense popularity. Having potential in reaching the hard‐to‐reach disease sites, this field has the potential to show high efficacy in combatting glioblastoma progression. The presence of glioblastoma stem cells (GSCs) is a major factor behind the poor prognosis of glioblastoma multiforme (GBM). Stemness potential, heterogeneity, and self‐renewal capacity, are some of the properties that make GSCs invade across the distant regions of the brain. Despite advances in medical technology and MRI‐guided maximal surgical resection, not all GSCs residing in the brain can be removed, leading to recurrent disease. The aggressiveness of GBM is often correlated with immune suppression, where the T‐cells are unable to infiltrate the cancer initiating GSCs. Standard of care therapies, including surgery and chemotherapy in combination with radiation therapy, have failed to tackle all the challenges of the GSCs, making it increasingly important for researchers to develop strategies to tackle their growth and proliferation and reduce the recurrence of GBM. Here, we will focus on the advancements in the field of nanomedicine that has the potential to show positive impact in managing glioblastoma tumor microenvironment. This article is categorized under:Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease [ABSTRACT FROM AUTHOR]

Hydrogels are materials made of crosslinked 3D networks of hydrophilic polymer chains that can absorb and retain significant amounts of water due to their hydrophilic structure without being dissolved. In relation to alternative biomaterials, hydrogels offer increased biocompatibility and biodegradability, giving them distinct advantages. Thus, hydrogel platforms are considered to have the potential for the development of biomedical applications. In this study, the main objective was the development of hybrid hydrogels to act as a drug delivery platform. These hydrogels were made from chitosan (CH) and type A gelatin (G), two natural polymers that provide a supportive environment for cellular attachment, viability, and growth, thanks to their unique properties. Particularly, the use of gelatins for drug delivery systems provides biodegradability, biocompatibility, and non-toxicity, which are excellent properties to be used in the human body. However, gelatins have some limitations, such as thermal instability and poor mechanical properties. In order to improve those properties, the aim of this work was the development and characterization of hybrid hydrogels with different ratios of CH–G (100–0, 75–25, 50–50, 25–75, 0–100). Hydrogels were characterized through multiple techniques, including Fourier transform infrared (FTIR) spectroscopy, rheological and microstructural studies, among others. Moreover, a model hydrophilic drug molecule (tetracycline) was incorporated to evaluate the feasibility of this platform to sustain the release of hydrophilic drugs, by being tested in a solution of Phosphate Buffer Solution at a pH of 7.2 and at 37 °C. The results revealed that the synergy between chitosan and type A gelatin improved the mechanical properties as well as the thermal stability of it, revealing that the best ratios of the biopolymers are 50–50 CH–G and 75–25 CH–G. Thereby, these systems were evaluated in a controlled release of tetracycline, showing a controlled drug delivery of 6 h and highlighting their promising application as a platform for controlled drug release. [ABSTRACT FROM AUTHOR]

Parasites, such as the malaria parasite P. falciparum, are critically dependent on host nutrients. Interference with nutrient uptake can lead to parasite death and, therefore, serve as a successful treatment strategy. P. falciparum parasites cannot synthesise cholesterol, and instead source this lipid from the host. Here, we tested whether cholesterol uptake pathways could be 'hijacked' for optimal drug delivery to the intracellular parasite. We found that fluorescent cholesterol analogues were delivered from the extracellular environment to the intracellular parasite. We investigated the uptake and inhibitory effects of conjugate compounds, where proven antimalarial drugs (primaquine and artesunate) were attached to steroids that mimic the structure of cholesterol. These conjugated antimalarial drugs improved the inhibitory effects against multiple parasite lifecycle stages, multiple parasite species, and drug-resistant parasites, whilst also lowering the toxicity to human host cells. Steroids with introduced peroxides also displayed antimalarial activity. These results provide a proof-of-concept that cholesterol mimics can be developed as a drug delivery system against apicomplexan parasites with the potential to improve drug efficacy, increase therapeutic index, and defeat drug resistance. Synopsis: Antimalarial drug resistance is a significant barrier to reducing malaria caused by Plasmodium parasites. The parasites scavenge cholesterol from the host, and the uptake pathways could be hijacked to deliver drugs directly to intracellular parasites, improving efficacy and overcoming resistance. Antimalarial drugs primaquine and artesunate were attached to steroid backbones to form drug conjugates which mimic the structure of cholesterol and take advantage of existing uptake pathways. The primaquine conjugate displayed better inhibitory effects against parasites at multiple lifecycle stages, with 2–14-fold improvement in 50% (IC50) and 90% (IC90) inhibitory concentrations. Parasite resistance to a frontline antimalarial compound, artesunate, was overcome with the conjugation strategy. Toxicity to human cells was lower in conjugate compounds than drug alone. This drug delivery system could improve drug efficacy and safety to reduce the burden of malaria. Antimalarial drug resistance is a significant barrier to reducing malaria caused by Plasmodium parasites. The parasites scavenge cholesterol from the host, and the uptake pathways could be hijacked to deliver drugs directly to intracellular parasites, improving efficacy and overcoming resistance. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are nano-sized, membranous transporters of various active biomolecules with inflicting phenotypic capabilities, that are naturally secreted by almost all cells with a promising vantage point as a potential leading drug delivery platform. The intrinsic characteristics of their low toxicity, superior structural stability, and cargo loading capacity continue to fuel a multitude of research avenues dedicated to loading EVs with therapeutic and diagnostic cargos (pharmaceutical compounds, nucleic acids, proteins, and nanomaterials) in attempts to generate superior natural nanoscale delivery systems for clinical application in therapeutics. In addition to their well-known role in intercellular communication, EVs harbor microRNAs (miRNAs), which can alter the translational potential of receiving cells and thus act as important mediators in numerous biological and pathological processes. To leverage this potential, EVs can be structurally engineered to shuttle therapeutic miRNAs to diseased recipient cells as a potential targeted 'treatment' or 'therapy'. Herein, this review focuses on the therapeutic potential of EV-coupled miRNAs; summarizing the biogenesis, contents, and function of EVs, as well as providing both a comprehensive discussion of current EV loading techniques and an update on miRNA-engineered EVs as a next-generation platform piloting benchtop studies to propel potential clinical translation on the forefront of nanomedicine. [ABSTRACT FROM AUTHOR]

Hydrogels are a 3D polymer network capable of absorbing large amounts of water or biological fluids without dissolving, due to chemical or physical crosslinking. They are made from cellulose derivatives and are a promising research area for developing smart drug carriers in modern drug delivery systems. The present research aimed to synthesize hydrogels based on nanocellulose derivatives and evaluate their antibacterial activity. A crosslinker termed epichlorohydrin (ECH) was incorporated into Sengon plant cellulose to produce cellulose derivatives, specifically abietic nanocellulose (CAB). Hydrogels were synthesized from the nanocellulose derivatives. The hydrogels were characterized using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM). The degree of substitution, release, and swelling tests, as well as antibacterial activity tests, were conducted. The results of the FTIR spectra revealed absorption between 1400 and 1600 cm-1, indicating a crosslinking process on the hydrogels. Furthermore, SEM cross-sectional observations demonstrated the formation of pores of various sizes. The hydrogel characterization results showed the impact of the preparation conditions, specifically the ECH concentration. The nanocellulose derivatives (NCAB): ECH concentration ratio varied between 1:0.5, 1:1, and 1:2. Based on the research results, the highest hydrogel swelling ratio was found in the CAB: ECH reaction conditions, which was 1:0.5. The findings of the present study demonstrated that modification by rosin esterification can result in hydrogels with desirable properties that can be employed for controlled drug delivery. Hydrogel from NCAB can inhibit the growth of E. coli bacteria in the weak category, but is moderate against S. aureus. [ABSTRACT FROM AUTHOR]

Cubosomes are the aqueous dispersions of lipid-based liquid-crystalline bi-continuous phases, with the inner structure comprised of triply periodic, non-intersecting, curved, bilayers folded in cubic symmetry, and are organized to form two disjoined continuous water channels on an infinite periodic minimal surface. This review emphasized the peer findings about history and origin of cubosomes, including preparation, characterization and evaluation techniques, along with its promising features as a bio-therapeutics biodegradable cargo nano-material in descriptive manner. The structures of cubosomes, e.g. Q223, Q227, Q212, Q230 etc. are discussed here reflecting their versatile applicability. The automated cubosome preparation method in addition to the general preparation methods and assessment of cubosomes with the aid of both, ordinary visual characterization as well as sophisticated instruments like cryo-TEM, Cryo-FESEM, SAXS, LUMiFuge® have been described. Physical parameter’s quantification approves the drug-carriers system fit in therapeutics, i.e stability analysis, permeation, entrapment efficiency (EE), loading capacity (LC), drug content of dispersions, in-vitro drug release studies, HPLC analysis, in-vivo studies, etc., which are framed here in detail. Cubosomes owes the versatility and desired characteristic of a nanoparticle for drug delivery and other biomedical applications. Therefore, we have described here the up to date wide area applications of cubosomes administered through various routes.

Chiral CDots (c‐CDots) not only inherit those merits from CDots but also exhibit chiral effects in optical, electric, and bio‐properties. Therefore, c‐CDots have received significant interest from a wide range of research communities including chemistry, physics, biology, and device engineers. They have already made decent progress in terms of synthesis, together with the exploration of their optical properties and applications. In this review, the chiroptical properties and chirality origin in extinction circular dichroism (ECD) and circularly polarized luminescence (CPL) of c‐CDots is briefly discussed. Then, the synthetic strategies of c‐CDots is summarized, including one‐pot synthesis, post‐functionalization of CDots with chiral ligands, and assembly of CDots into chiral architectures with soft chiral templates. Afterward, the chiral effects on the applications of c‐CDots are elaborated. Research domains such as drug delivery, bio‐ or chemical sensing, regulation of enzyme‐like catalysis, and others are covered. Finally, the perspective on the challenges associated with the synthetic strategies, understanding the origin of chirality, and potential applications is provided. This review not only discusses the latest developments of c‐CDots but also helps toward a better understanding of the structure‐property relationship along with their respective applications. [ABSTRACT FROM AUTHOR]

Cubosomes are the aqueous dispersions of lipid-based liquid-crystalline bi-continuous phases, with the inner structure comprised of triply periodic, non-intersecting, curved, bilayers folded in cubic symmetry, and are organized to form two disjoined continuous water channels on an infinite periodic minimal surface. This review emphasized the peer findings about history and origin of cubosomes, including preparation, characterization and evaluation techniques, along with its promising features as a bio-therapeutics biodegradable cargo nano-material in descriptive manner. The structures of cubosomes, e.g. Q223, Q227, Q212, Q230 etc. are discussed here reflecting their versatile applicability. The automated cubosome preparation method in addition to the general preparation methods and assessment of cubosomes with the aid of both, ordinary visual characterization as well as sophisticated instruments like cryo-TEM, Cryo-FESEM, SAXS, LUMiFuge® have been described. Physical parameter's quantification approves the drug-carriers system fit in therapeutics, i.e stability analysis, permeation, entrapment efficiency (EE), loading capacity (LC), drug content of dispersions, in-vitro drug release studies, HPLC analysis, in-vivo studies, etc., which are framed here in detail. Cubosomes owes the versatility and desired characteristic of a nanoparticle for drug delivery and other biomedical applications. Therefore, we have described here the up to date wide area applications of cubosomes administered through various routes. [ABSTRACT FROM AUTHOR]

Interdisciplinary sciences have paved the way for the creation of new technologies that could potentially alter how things were conventionally done. Biotechnology and nanotechnology have resulted in the creation of various techniques, one of which is upconversion nanoparticles (UCNPs), which can be conjugated with biomaterials for added functionality. UCNPs work based on optical phenomena referred to as anti-Stoke shift, wherein the nanoparticle absorbs light of a high wavelength (lower energy) and emits light having a lower wavelength (higher energy). This ability to provide luminescent signals when irradiated with near-infrared (NIR) light sources is particularly useful as a consequence of its minimal toxicity and high depth of penetration. When coupled with the appropriate biomaterials, the UCNPs can conjugate with the target under study and via quenching/luminescence recovery and quantitative and qualitative tests can be performed relating to the target molecule, in vivo. These UCNP-nanomaterial structures have proven to be very useful in the in vivo image detection, diagnostic, therapeutic as well as combined approaches for disease treatment, drug delivery, disease diagnosis etc. This review aims at providing an in-depth explanation about the origins of UCNPs, how they may be synthesized, their mechanisms of upconversion (UC), their adaptability and flexibility under in vivo conditions, and the future of the field. Overall representation of Upconverting Nanoparticle (UCNP) synthesis followed by the currently researched/applied modes of utilization for the same. The drug delivery aspect involves loading the porous layer over the UCNP with the required drug while the bio-imaging and therapeutic application (via photothermal therapy and/or photodynamic therapy) involves irradiation of the nanoparticles by tissue-penetrating near-infrared radiation (NIR). [ABSTRACT FROM AUTHOR]

Microbubble‐enabled focused ultrasound (MB‐FUS) has revolutionized nano and molecular drug delivery capabilities. Yet, the absence of longitudinal, systematic, quantitative studies of microbubble shell pharmacokinetics hinders progress within the MB‐FUS field. Microbubble radiolabeling challenges contribute to this void. This barrier is overcome by developing a one‐pot, purification‐free copper chelation protocol able to stably radiolabel diverse porphyrin‐lipid‐containing Definity® analogues (pDefs) with >95% efficiency while maintaining microbubble physicochemical properties. Five tri‐modal (ultrasound‐, positron emission tomography (PET)‐, and fluorescent‐active) [64Cu]Cu‐pDefs are created with varying lipid acyl chain length and charge, representing the most prevalently studied microbubble compositions. In vitro, C16 chain length microbubbles yield 2–3x smaller nanoprogeny than C18 microbubbles post FUS. In vivo, [64Cu]Cu‐pDefs are tracked in healthy and 4T1 tumor‐bearing mice ± FUS over 48 h qualitatively through fluorescence imaging (to characterize particle disruption) and quantitatively through PET and γ‐counting. These studies reveal the impact of microbubble composition and FUS on microbubble dissolution rates, shell circulation, off‐target tissue retention (predominantly the liver and spleen), and FUS enhancement of tumor delivery. These findings yield pharmacokinetic microbubble structure‐activity relationships that disrupt conventional knowledge, the implications of which on MB‐FUS platform design, safety, and nanomedicine delivery are discussed. [ABSTRACT FROM AUTHOR]

Abstract Chiral CDots (c‐CDots) not only inherit those merits from CDots but also exhibit chiral effects in optical, electric, and bio‐properties. Therefore, c‐CDots have received significant interest from a wide range of research communities including chemistry, physics, biology, and device engineers. They have already made decent progress in terms of synthesis, together with the exploration of their optical properties and applications. In this review, the chiroptical properties and chirality origin in extinction circular dichroism (ECD) and circularly polarized luminescence (CPL) of c‐CDots is briefly discussed. Then, the synthetic strategies of c‐CDots is summarized, including one‐pot synthesis, post‐functionalization of CDots with chiral ligands, and assembly of CDots into chiral architectures with soft chiral templates. Afterward, the chiral effects on the applications of c‐CDots are elaborated. Research domains such as drug delivery, bio‐ or chemical sensing, regulation of enzyme‐like catalysis, and others are covered. Finally, the perspective on the challenges associated with the synthetic strategies, understanding the origin of chirality, and potential applications is provided. This review not only discusses the latest developments of c‐CDots but also helps toward a better understanding of the structure‐property relationship along with their respective applications.

Hydrogels are materials made of crosslinked 3D networks of hydrophilic polymer chains that can absorb and retain significant amounts of water due to their hydrophilic structure without being dissolved. In relation to alternative biomaterials, hydrogels offer increased biocompatibility and biodegradability, giving them distinct advantages. Thus, hydrogel platforms are considered to have the potential for the development of biomedical applications. In this study, the main objective was the development of hybrid hydrogels to act as a drug delivery platform. These hydrogels were made from chitosan (CH) and type A gelatin (G), two natural polymers that provide a supportive environment for cellular attachment, viability, and growth, thanks to their unique properties. Particularly, the use of gelatins for drug delivery systems provides biodegradability, biocompatibility, and non-toxicity, which are excellent properties to be used in the human body. However, gelatins have some limitations, such as thermal instability and poor mechanical properties. In order to improve those properties, the aim of this work was the development and characterization of hybrid hydrogels with different ratios of CH–G (100–0, 75–25, 50–50, 25–75, 0–100). Hydrogels were characterized through multiple techniques, including Fourier transform infrared (FTIR) spectroscopy, rheological and microstructural studies, among others. Moreover, a model hydrophilic drug molecule (tetracycline) was incorporated to evaluate the feasibility of this platform to sustain the release of hydrophilic drugs, by being tested in a solution of Phosphate Buffer Solution at a pH of 7.2 and at 37 °C. The results revealed that the synergy between chitosan and type A gelatin improved the mechanical properties as well as the thermal stability of it, revealing that the best ratios of the biopolymers are 50–50 CH–G and 75–25 CH–G. Thereby, these systems were evaluated in a controlled release of tetracycline, showing a controlled drug delivery of 6 h and highlighting their promising application as a platform for controlled drug release.

Abstract Arsenic trioxide (ATO) is a promising chemotherapeutic agent, but its clinical application is limited due to its poor pharmacokinetics and dose-limited toxicity. Moreover, the combination of ATO and sec-o-glucosylhamaudol (SOG) can improve the therapeutic effect of hepatoma. In this study, PEGylated magnetic nanographene oxide (PEG@MGO) was used as magnetic carriers to enhance the targeting ability of the drug delivery system. ATO and SOG are loaded on the surface of PEG@MGO nanoparticles through electrostatic interactions. This biocompatible nanocomposite shows magnetic susceptibility, pH sensitivity, and high loading capacity of the drugs. The in vitro cytotoxicity study of human hepatoma cell line (HepG2) cells showed more significant cytotoxicity and obvious synergistic effect between ATO and SOG compared with that of single drug-loaded nanoparticles via MTT assay. In vitro cellular uptake was observed by Prussian blue staining and fluorescently labeling. The results demonstrated a high cellular internalization rate of PEG@MGO. The ATO and SOG co-loaded nanodrug significantly inhibits the growth of tumors in vivo, which might be due to the oxidative stress and proapoptotic effect. This type of multidrug nanocomposite offers a promising alternative for cancer therapy. Graphical Abstract A pH-sensitive polyethylene glycol-modified magnetic graphene oxide loaded with ATO and SOG (PEG@MGO@ATO + SOG) was prepared for the magnetically targeted and efficient synergistic-chemo cancer therapy, which exhibited high specificity and good biocompatibility.

Abstract Microbubble‐enabled focused ultrasound (MB‐FUS) has revolutionized nano and molecular drug delivery capabilities. Yet, the absence of longitudinal, systematic, quantitative studies of microbubble shell pharmacokinetics hinders progress within the MB‐FUS field. Microbubble radiolabeling challenges contribute to this void. This barrier is overcome by developing a one‐pot, purification‐free copper chelation protocol able to stably radiolabel diverse porphyrin‐lipid‐containing Definity® analogues (pDefs) with >95% efficiency while maintaining microbubble physicochemical properties. Five tri‐modal (ultrasound‐, positron emission tomography (PET)‐, and fluorescent‐active) [64Cu]Cu‐pDefs are created with varying lipid acyl chain length and charge, representing the most prevalently studied microbubble compositions. In vitro, C16 chain length microbubbles yield 2–3x smaller nanoprogeny than C18 microbubbles post FUS. In vivo, [64Cu]Cu‐pDefs are tracked in healthy and 4T1 tumor‐bearing mice ± FUS over 48 h qualitatively through fluorescence imaging (to characterize particle disruption) and quantitatively through PET and γ‐counting. These studies reveal the impact of microbubble composition and FUS on microbubble dissolution rates, shell circulation, off‐target tissue retention (predominantly the liver and spleen), and FUS enhancement of tumor delivery. These findings yield pharmacokinetic microbubble structure‐activity relationships that disrupt conventional knowledge, the implications of which on MB‐FUS platform design, safety, and nanomedicine delivery are discussed.

Knowing the beneficial aspects of nanomedicine, scientists are trying to harness the applications of nanotechnology in diagnosis, treatment, and prevention of diseases. There are also potential uses in designing medical tools and processes for the new generation of medical scientists. The main objective for conducting this research review is to gather the widespread aspects of nanomedicine under one heading and to highlight standard research practices in the medical field. Comprehensive research has been conducted to incorporate the latest data related to nanotechnology in medicine and therapeutics derived from acknowledged scientific platforms. Nanotechnology is used to conduct sensitive medical procedures. Nanotechnology is showing successful and beneficial uses in the fields of diagnostics, disease treatment, regenerative medicine, gene therapy, dentistry, oncology, aesthetics industry, drug delivery, and therapeutics. A thorough association of and cooperation between physicians, clinicians, researchers, and technologies will bring forward a future where there is a more calculated, outlined, and technically programed field of nanomedicine. Advances are being made to overcome challenges associated with the application of nanotechnology in the medical field due to the pathophysiological basis of diseases. This review highlights the multipronged aspects of nanomedicine and how nanotechnology is proving beneficial for the health industry. There is a need to minimize the health, environmental, and ethical concerns linked to nanotechnology. [ABSTRACT FROM AUTHOR]

In this article, the hemodynamics of nanofluid flow through the modelled stenosis-aneurysm models in the presence of the catheter has been studied. The eight stenosis-aneurysm models are developed to mimic biological observations and thus make the model more realistic. The mathematical understanding helps in treating the stenosis in the blood vessel by targeting the unhealthy region to the drug, which is coated on nanoparticles. The catheter achieves the active drug release to the aimed organs by coating on the catheter surface, which adds additional benefits. In the present hemodynamic study, the blood is modeled as a couple stress fluid; as a result, the highly non-linear momentum, temperature, and concentration equations were obtained. The fluid flow equations' complexity is further increased by incorporating the variable viscosity effects that arose due to the suspension of nanoparticles. The resultant mathematical model is solved by using the homotopy perturbation method. The convergence of the perturbed solutions is studied and depicted the degree of deformation in the case of temperature and concentration. The effects of the porous nature of the stenosis, no-slip at the catheter surface, and the free slip at the blood vessel boundary in the non-stenotic region are also considered in the model. The essential physiological property like surface shear stress is computed, and various parameters' influence on shear stress is analyzed. The present analysis can be helpful in understanding the enhancement in mass dispersion and heat transfer in unhealthy blood vessels, which could be used for drug delivery in the treatment of stenotic conditions. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Cancer Biotherapy is the property of Editorial Office of Chinese Journal of Cancer Biotherapy and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background The 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. Results The 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. Conclusion The 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 Abstract

This study investigates the hemodynamics of nanofluid flow through modelled stenosis-aneurysm models. The models were created using mathematical functions to increase their realism. This study aims to explore how temperature-sensitive drugs coated on nanoparticles could be delivered to diseased areas, with the mathematical model aiding in the treatment of vascular stenosis. To effectively treat stenosis, medication-coated nanoparticles should be applied to the exterior surface of a catheter. The blood flow was modelled as a micropolar fluid flow, which led to the development of highly nonlinear coupled equations for momentum, temperature, and concentration. The dispersion of nanoparticles resulted in changing viscosity effects, making the fluid flow equations even more complex. The model considered the porous nature of the stenosis, no-slip at the catheter surface, and free slip at the blood vessel surface. The homotopy perturbation method was used to solve the formulated mathematical model. The study investigated the convergence of perturbed solutions for temperature and concentration and showed the degree of deformation. Drug delivery to a targeted region is faster in a converging tapered blood vessel than in a diverging and non-tapered artery. Concentration dispersion is more significant in the stenotic region, while temperature dispersion is more significant in the aneurysm region. The results of the study can be used to understand the improvement in mass dispersion and heat transfer in unhealthy blood arteries, which may be useful in delivering drugs to treat stenotic diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] Sustainably derived poly(glycerol adipate) (PGA) has been deemed to deliver all the desirable features expected in a polymeric scaffold for drug-delivery, including biodegradability, biocompatibility, self-assembly into nanoparticles (NPs) and a functionalisable pendant group. Despite showing these advantages over commercial alkyl polyesters, PGA suffers from a series of key drawbacks caused by poor amphiphilic balance. This leads to weak drug-polymer interactions and subsequent low drug-loading in NPs, as well as low NPs stability. To overcome this, in the present work, we applied a more significant variation of the polyester backbone while maintaining mild and sustainable polymerisation conditions. We have investigated the effect of the variation of both hydrophilic and hydrophobic segments upon physical properties and drug interactions as well as self-assembly and NPs stability. For the first time we have replaced glycerol with the more hydrophilic diglycerol, as well as adjusting the final amphiphilic balance of the polyester repetitive units by incorporating the more hydrophobic 1,6- n -hexanediol (Hex). The properties of the novel poly(diglycerol adipate) (PDGA) variants have been compared against known polyglycerol-based polyesters. Interestingly, while the bare PDGA showed improved water solubility and diminished self-assembling ability, the Hex variation demonstrated enhanced features as a nanocarrier. In this regard, PDGAHex NPs were tested for their stability in different environments and for their ability to encode enhanced drug loading. Moreover, the novel materials have shown good biocompatibility in both in vitro and in vivo (whole organism) experiments. [ABSTRACT FROM AUTHOR]

Arsenic trioxide (ATO) is a promising chemotherapeutic agent, but its clinical application is limited due to its poor pharmacokinetics and dose-limited toxicity. Moreover, the combination of ATO and sec-o-glucosylhamaudol (SOG) can improve the therapeutic effect of hepatoma. In this study, PEGylated magnetic nanographene oxide (PEG@MGO) was used as magnetic carriers to enhance the targeting ability of the drug delivery system. ATO and SOG are loaded on the surface of PEG@MGO nanoparticles through electrostatic interactions. This biocompatible nanocomposite shows magnetic susceptibility, pH sensitivity, and high loading capacity of the drugs. The in vitro cytotoxicity study of human hepatoma cell line (HepG2) cells showed more significant cytotoxicity and obvious synergistic effect between ATO and SOG compared with that of single drug-loaded nanoparticles via MTT assay. In vitro cellular uptake was observed by Prussian blue staining and fluorescently labeling. The results demonstrated a high cellular internalization rate of PEG@MGO. The ATO and SOG co-loaded nanodrug significantly inhibits the growth of tumors in vivo, which might be due to the oxidative stress and proapoptotic effect. This type of multidrug nanocomposite offers a promising alternative for cancer therapy. A pH-sensitive polyethylene glycol-modified magnetic graphene oxide loaded with ATO and SOG (PEG@MGO@ATO + SOG) was prepared for the magnetically targeted and efficient synergistic-chemo cancer therapy, which exhibited high specificity and good biocompatibility. [ABSTRACT FROM AUTHOR]

One of the components of bee venom is melittin (M), which has strong lysing properties on membranes. M has high toxicity to cancer cells, but it also affects healthy cells, making it necessary to use methods for targeted delivery to ensure treatment. This research is a continuation of previous studies using graphene nanomaterials as M carriers to breast cancer cells. The studies described below are conducted on a more organized biological structure than what is found in vitro cells, namely, cancerous tumors grown on a chicken embryo chorioallantoic membrane. Caspase 3 and 8 levels are analyzed, and the level of oxidative stress markers and changes in protein expression for cytokines are examined. The results show that M complexes with nanomaterials reduce the level of oxidative stress more than M alone does, but the use of graphene (GN) as a carrier increases the level of DNA damage to a greater extent than the increase caused by M alone. An analysis of cytokine levels shows that the use of the M and GN complex increases the level of proteins responsible for inhibiting tumor progression to a greater extent than the increase occasioned by a complex with graphene oxide (GO). The results suggest that the use of GN as an M carrier may increase the toxic effect of M on structures located inside a cell. [ABSTRACT FROM AUTHOR]

This study aimed to synthesize Carboxymethylated Gum Tragacanth (CMGT) from the Gum Tragacanth (GT). Modified gum's potential as a drug delivery carrier has been explored by synthesizing CMGT based hydrogels. The viscoelastic characteristics of the fabricated hydrogel have been examined by Rheological analysis. SEM studies have been conducted to examine the surface morphology and TGA is used to perform the thermal analysis. XRD, FTIR, and solid state 13C NMR have been used to examine the structural features of the GT, CMGT, sodium acrylate based hydrogel (SAH) and carboxymethylated gum tragacanth co-polymerized with sodium acrylate based hydrogel (CMGT-co-SAH). The anti-inflammatory drug, Aceclofenac Sodium(AFS) loaded onto the hydrogel has been used as a model drug. The AFS follows the Fickian mechanism of diffusion and the results are best fitted in Higuchi and Korsmeyer-Peppas models. [ABSTRACT FROM AUTHOR]

A highly selective molecularly imprinted polymer (MIP) to 4-Aminopyridine (4-Ap) target was synthesized starting with azobenzene monomers, which cross-linked initiated by 2, 2′‐azobisisobutyronitrile with the ethylene glycol dimethacrylate. The obtained sorbent, comprised of light-thermosensitive functions, was characterized using FTIR and SEM. The product was finally employed for the 4-AP target in solid-phase extraction. The effect of optimal parameters in the process was studied. The adsorption and release processes for 4-Ap drug delivery were investigated under various conditions, including temperature and radiation wavelengths. This study suggests a facile determination method high selectivity to 4-Ap adsorption/release in a real sample. [ABSTRACT FROM AUTHOR]

Osteosarcoma is a malignant tumor of bone that leads to poor mortality and morbidity. Management of this cancer through conventional methods involves invasive treatment options that place patients at an increased risk of adverse events. The use of hydrogels to target osteosarcoma has shown promising results both in vitro and in vivo to eradicate tumor cells while promoting bone regeneration. The loading of hydrogels with chemotherapeutic drugs provides a route for site-specific targeted therapy for osteosarcoma. Current studies demonstrate tumor regression in vivo and lysis of tumor cells in vitro when exposed to doped hydrogel scaffolds. Additionally, novel stimuli-responsive hydrogels are able to react with the tissue microenvironment to facilitate the controlled release of anti-tumor drugs and with biomechanical properties that can be modulated. This narrative review of the current literature discusses both in vitro and in vivo studies of different hydrogels, including stimuli-responsive, designed to treat bone osteosarcoma. Future applications to address patient treatment for this bone cancer are also discussed. [ABSTRACT FROM AUTHOR]

The development of chemotherapies for glioblastoma is hindered by their limited bioavailability and toxicity on normal brain function. To overcome these limitations, we investigated the structure‐dependent activity of heptamethine cyanine dyes (HMCD), a group of tumour‐specific and BBB permeable near‐infrared fluorescent dyes, in both commercial (U87MG) and patient‐derived GBM cell lines. HMCD analogues with strongly ionisable sulphonic acid groups were not taken up by patient‐derived GBM cells, but were taken up by the U87MG cell line. HMCD uptake relies on a combination of transporter uptake through organic anion‐transporting polypeptides (OATPs) and endocytosis into GBM cells. The uptake of HMCDs was not affected by p‐glycoprotein efflux in GBM cells. Finally, we demonstrate structure‐dependent cytotoxic activity at high concentrations (EC50: 1–100 μM), likely due to mitochondrial damage‐induced apoptosis. An in vivo orthotopic glioblastoma model highlights tumour‐specific accumulation of our lead HMCD, MHI‐148, for up to 7 days following a single intraperitoneal injection. These studies suggest that strongly ionisable groups like sulphonic acids hamper the cellular uptake of HMCDs in patient‐derived GBM cell lines, highlighting cell line‐specific differences in HMCD uptake. We envisage these findings will help in the design and structural modifications of HMCDs for drug‐delivery applications for glioblastoma. [ABSTRACT FROM AUTHOR]

Retinal eye diseases are the leading cause of blindness in the Western world. Up to date, the only efficient treatment for many retinal diseases consists of invasive intravitreal injections of highly concentrated drugs. Despite the fact that these injections are unpleasant for the patients, they potentially cause serious side effects, e.g., infections, bleeding within the eye or retinal detachment, especially when performed on a monthly basis, thus decreasing the injection frequency and lowering the desired drug dose. Therefore, a sustained released at the region of interest with a sustained release is desired. Recently, novel lipid-DNA nanoparticles (NPs) were shown to be an efficient drug delivery platform to the anterior segment of the eye. In this study, we investigated the distribution and tropism of the NPs when applied intravitreally, as a potential medication carrier to the posterior part of the eye. This technology is perfectly suited for the delivery of low molecular weight drugs to the back of the eye, which so far is greatly hindered by fast diffusion rates of the free drugs in the vitreous body and their intrinsically low retainability in ocular tissue. Excellent biodistribution, adherence and presence for up to five days was found for the different tested nanoparticles ex vivo and in vivo. In conclusion, our lipid-DNA based nanocarrier system was able to reach the retina within minutes and penetrate the retina providing potentially safe and long-term carrier systems for small molecules or nucleotide-based therapies. [ABSTRACT FROM AUTHOR]

To improve currently available cancer treatments, nanomaterials are employed as smart drug delivery vehicles that can be engineered to locally target cancer cells and respond to stimuli. Nanocarriers can entrap chemotherapeutic drugs and deliver them to the diseased site, reducing the side effects associated with the systemic administration of conventional anticancer drugs. Upon accumulation in the tumor cells, the nanocarriers need to be potentiated to release their therapeutic cargo. Stimulation can be through endogenous or exogenous modalities, such as temperature, electromagnetic irradiation, ultrasound (US), pH, or enzymes. This review discusses the acoustic stimulation of different sonosensitive liposomal formulations. Emulsion liposomes, or eLiposomes, are liposomes encapsulating phase-changing nanoemulsion droplets, which promote acoustic droplet vaporization (ADV) upon sonication. This gives eLiposomes the advantage of delivering the encapsulated drug at low intensities and short exposure times relative to liposomes. Other formulations integrating microbubbles and nanobubbles are also discussed. [ABSTRACT FROM AUTHOR]

There has been extensive research on improving and innovating current treatments for irritable-bowel-syndrome using nanotechnology. However, there are growing challenges to progress these drugs to clinical trials and commercialisation. This study sought to develop a framework to manage key features, overlooked in current studies, to improve the development of drugs. An integrative literature review was used to extract themes by using a summative content analysis to interrogate information. Validity was established when saturation of information was achieved. Reliability focussed on the repeatability of key information. Absorption, distribution, metabolism, excretion and toxicity, quality by design attributes, metrology, and standardisation of practice emerged as important themes. These themes together among others, were used to develop the framework to manage the drug development process: Knowledge-based society, Foresight planning, Multidisciplinary approach, Unified definition, Adapt to existing standards and guidelines, Precautionary principle, Case-by-case approach, Quality-by-design, Scale-up and Training. The framework provided reflections that no study has considered. The framework will ensure that drug development will be approached strategically to avoid duplication of research-designs, including risk mitigation, quality at the source and supplier-chain management to progress drug development to clinical trials and beyond.

Nóra Igaz,1 Péter Bélteky,2 Dávid Kovács,1,3 Csaba Papp,4 Andrea Rónavári,2 Diána Szabó,5 Attila Gácser,4 Zoltán Kónya,2,6 Mónika Kiricsi1 1Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary; 2Department of Applied and Environmental Chemistry, University of Szeged, Szeged, Hungary; 3Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d’Azur, Inserm, CNRS, Valbonne, France; 4HCEMM-USZ Fungal Pathogens Research Group, Department of Microbiology, University of Szeged, Szeged, Hungary; 5Department of Oto-Rhino-Laryngology and Head & Neck Surgery, Szeged, Hungary; 6Eötvös Loránd Research Network, Reaction Kinetics and Surface Chemistry Research Group, Szeged, HungaryCorrespondence: Mónika Kiricsi, Department of Biochemistry and Molecular Biology, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary, Tel +36 (62) 544-887, Email kiricsim@bio.u-szeged.hu Zoltán Kónya, Department of Applied and Environmental Chemistry, University of Szeged, Rerrich square 1, Szeged, H-6720, Hungary, Tel +36 (62) 544620, Email konya@chem.u-szeged.huBackground: Multidrug resistance is a common reason behind the failure of chemotherapy. Even if the therapy is effective, serious adverse effects might develop due to the low specificity and selectivity of antineoplastic agents. Mesoporous silica nanoparticles (MSNs) are promising materials for tumor-targeting and drug-delivery due to their small size, relatively inert nature, and extremely large specific surfaces that can be functionalized by therapeutic and targeting entities. We aimed to create a fluorescently labeled MSN-based drug-delivery system and investigate their internalization and drug-releasing capability in drug-sensitive MCF-7 and P-glycoprotein-overexpressing multidrug-resistant MCF-7 KCR cancer cells.Methods and Results: To track the uptake and subcellular distribution of MSNs, particles with covalently coupled red fluorescent Rhodamine B (RhoB) were produced (RhoB@MSNs). Both MCF-7 and MCF-7 KCR cells accumulated a significant amount of RhoB@MSNs. The intracellular RhoB@MSN concentrations did not differ between sensitive and multidrug-resistant cells and were kept at the same level even after cessation of RhoB@MSN exposure. Although most RhoB@MSNs resided in the cytoplasm, significantly more RhoB@MSNs co-localized with lysosomes in multidrug-resistant cells compared to sensitive counterparts. To examine the drug-delivery capability of these particles, RhoB@Rho123@MSNs were established, where RhoB-functionalized nanoparticles carried green fluorescent Rhodamine 123 (Rho123) - a P-glycoprotein substrate – as cargo within mesopores. Significantly higher Rho123 fluorescence intensity was detected in RhoB@Rho123@MSN-treated multidrug-resistant cells than in free Rho123-exposed counterparts. The exceptional drug-delivery potential of MSNs was further verified using Mitomycin C (MMC)-loaded RhoB@MSNs (RhoB@MMC@MSNs). Exposures to RhoB@MMC@MSNs significantly decreased the viability not only of drug-sensitive but of multidrug-resistant cells and the elimination of MDR cells was significantly more robust than upon free MMC treatments.Conclusion: The efficient delivery of Rho123 and MMC to multidrug-resistant cells via MSNs, the amplified and presumably prolonged intracellular drug concentration, and the consequently enhanced cytotoxic effects envision the enormous potential of MSNs to defeat multidrug-resistant cancer.Graphical Abstract: Keywords: mesoporous silica nanoparticles, drug-delivery, fluorescently labeled MSNs, functionalized MSNs, multidrug resistance

Chitosan is an interesting polymer to produce hydrogels suitable for the 3D printing of customized drug delivery systems. This study aimed at the achievement of chitosan-based scaffolds suitable for the incorporation of active components in the matrix or loaded into the pores. Several scaffolds were printed using different chitosan-based hydrogels. To understand which parameters would have a greater impact on printability, an optimization study was conducted. The scaffolds with the highest printability were obtained with a chitosan hydrogel at 2.5 wt%, a flow speed of 0.15 mm/s and a layer height of 0.41 mm. To improve the chitosan hydrogel printability, starch was added, and a design of experiments with three factors and two responses was carried out to find out the optimal starch supplementation. It was possible to conclude that the addition of starch (13 wt%) to the chitosan hydrogel improved the structural characteristics of the chitosan-based scaffolds. These scaffolds showed potential to be tested in the future as drug-delivery systems. [ABSTRACT FROM AUTHOR]

There has been extensive research on improving and innovating current treatments for irritable-bowel-syndrome using nanotechnology. However, there are growing challenges to progress these drugs to clinical trials and commercialisation. This study sought to develop a framework to manage key features, overlooked in current studies, to improve the development of drugs. An integrative literature review was used to extract themes by using a summative content analysis to interrogate information. Validity was established when saturation of information was achieved. Reliability focussed on the repeatability of key information. Absorption, distribution, metabolism, excretion and toxicity, quality by design attributes, metrology, and standardisation of practice emerged as important themes. These themes together among others, were used to develop the framework to manage the drug development process: Knowledge-based society, Foresight planning, Multidisciplinary approach, Unified definition, Adapt to existing standards and guidelines, Precautionary principle, Case-by-case approach, Quality-by-design, Scale-up and Training. The framework provided reflections that no study has considered. The framework will ensure that drug development will be approached strategically to avoid duplication of research-designs, including risk mitigation, quality at the source and supplier-chain management to progress drug development to clinical trials and beyond. [ABSTRACT FROM AUTHOR]

Tumor growth and progression are strictly dependent on the adequate blood supply of oxygen and nutrients. The formation of new blood vessels and vascular networks is essential to ensure this demand. Blood vessels also facilitate the invasion of cancer cells into nearby tissues and their subsequent metastasis. Tumor cells represent the main driver of the neovascularization process through the direct or indirect, by neighboring non-cancer cells, release of pro-angiogenic molecules. The mediators (e.g., growth factors and extracellular matrix components), signaling pathways, cellular components, and processes (e.g., endothelial cell proliferation and migration) activated in tumor angiogenesis are similar to those involved in normal vascular development, except they lack efficient control mechanisms. Consequently, newly formed tumor vessels are typically fragile and hyperpermeable with a reduced and erratic blood flow. Targeting the tumor vasculature has been the focus of intense research over the last 20 years. However, despite the initial interest and expectations, the systemic use of anti-angiogenic drugs has not always led to therapeutic breakthroughs and, in some cases, has been associated with the development of tumor adaptive resistance resulting in a more aggressive phenotype. Therefore, new therapeutic approaches have focused on combining anti-angiogenic agents with chemotherapy or immunotherapy and/or optimizing (normalizing) the structure and function of tumor blood vessels to ensure a more efficient drug delivery. In this context, nanomedicine offers the significant advantage of targeting and releasing anti-angiogenic drugs at specific sites, minimizing toxicity in healthy tissues. Several nanoparticles possess intrinsic modulatory effects on angiogenesis, while others have been developed to facilitate drug delivery in association with chemotherapy, thermotherapy, radiotherapy or in response to specific stimuli within the tumor environment (e.g., enzymes, ions, redox potential) or exogenous stimuli (e.g., temperature, electricity, magnetic fields, and ultrasound). Other nanoparticles can modify, under specific conditions, their physical properties (e.g., dimensions, structure, and interactions) to increase penetration in tumor cells. This review provides a comprehensive appraisal of the critical modulators of tumor vascular biology, the most promising nano-strategies that specifically target such modulators, and the directions for future research and clinical applications. [ABSTRACT FROM AUTHOR]

Composite bio-based hydrogels have been obtaining a significant attention in recent years as one of the most promising drug delivery systems. In the present study, the preparation of composite chitosan-starch hydrogel using maleic acid as a cross-linker was optimized with the help of response surface methodology. The synthesized hydrogel was fluorescent owing to clustering of large number of functional groups. Different analytical techniques, including XRD, FTIR, SEM, XPS, fluorescence and BET were utilized to characterize the prepared hydrogel. XRD analysis confirmed the formation of non-crystalline hydrogel with random arrangement of macromolecular chains. The composite hydrogel exhibited good swelling percentage with pH sensitivity, hemocompatibility and degradability. BET analysis confirmed that the variation in concentration of crosslinker significantly influences the pore volume of the hydrogel. The synthesized composite chitosan-starch hydrogel was utilized as a prospective candidate for controlling drug release. Cefixime as a model drug was loaded onto the synthesized hydrogel utilizing the swelling diffusion method. SEM micrographs showed uniform distribution of drug molecules in the drug loaded hydrogel. In vitro drug release experiments indicated the swelling dependent drug release behaviour of chitosan-starch hydrogel with higher drug release at pH 7.4 (93.08 %) compared to pH 1.2 (67.85 %). The composite chitosan-starch hydrogel was able to prolong and control the drug release up to 12 h. The drug release from the hydrogel followed Korsmeyer-Peppas and Makoid-Banakar model with Fickian diffusion mechanism. Further, the composite hydrogel displayed excitation dependent fluorescence emission with most intense blue emission band at 425 nm with an excitation wavelength of 350 nm. The inclusion of cefixime drug in the hydrogel matrix significantly reduced the fluorescence intensity; the decrease was linearly correlated to the concentration of the drug. Moreover, the fluorescence emission the chitosan-starch hydrogel was found to be dependent upon pH. The synthesized hydrogel is expected to be a potential candidate for controlled drug release as well as for fluorescent sensing applications. • A biodegradable biopolymeric hydrogel of chitosan-starch was developed via chemical crosslinking using free radical polymerization • The synthesized hydrogel was fluorescent owing to clustering of large number of functional groups. • The chitosan-starch hydrogel was found to be a potential candidate for controlled drug delivery and fluorescent sensing applications. [ABSTRACT FROM AUTHOR]

Abstract With the growing demands for personalized medicine and medical devices, nanomedicine is a modern scientific field, and research continues to apply nanomaterials for therapeutic and damaged tissue diagnosis. In this regard, substantial progress has been made in synthesizing magnetic nanoparticles with desired sizes, chemical composition, morphologies, and surface chemistry. Among these materials, nanomagnetic iron oxides have demonstrated promise as unique drug delivery carriers due to cancer treatment. This carrier could lead to responsive properties to a specific trigger, including heat, pH, alternative magnetic field, or even enzymes, through functionalization and coating of magnetic nanoparticles, along with biocompatibility, good chemical stability, easy functionalization, simple processing, and ability to localize to the tumor site with the assistance of external magnetic field. Current studies have focused on magnetic nanoparticles’ utilities in cancer therapy, especially for colorectal cancer. Additionally, a bibliometric investigation was performed on the public trends in the field of the magnetic nanoparticle to drug delivery and anticancer, which represented progressing applications of these carriers in the multidisciplinary zones with a general view on future research and identified potential opportunities and challenges. Furthermore, we outline the current challenges and forthcoming research perspective for high performance and fostering advanced MNPs in colorectal cancer treatment. Graphical Abstract

This study investigate the effect of process parameters on the size, distribution, zeta potential and loading efficiency for the co-delivery of liposomal formulation of Ran-RCC1 inhibitory peptide (RANIP) and doxorubicin (DOX) to breast cancer. The results show that drug concentration, pH and ultrasound intensity are all critical factors to control the attributes of the liposomes.

Current therapeutic treatments for the repair and/or replacement of damaged skin following disease or traumatic injury is severely limited. The chicken eggshell membrane (ESM) is a unique material: its innate physical and mechanical characteristics offer optimal barrier properties and, as a naturally derived extract, it demonstrates inherent biocompatibility/biodegradability. To further enhance its therapeutic and clinical potential, the ESM can be modified with the thermo-responsive polymer, poly(N-isopropylacrylAmide) (PNIPAAm) as well as the incorporation of (drug-loaded) silver nanoparticles (AgNP); essentially, by a simple change in temperature, the release and delivery of the NP can be targeted and controlled. In this study, ESM samples were isolated using a decellularization protocol, and the physical and mechanical characteristics were profiled using SEM, FT-IR, DSC and DMA. PNIPAAm was successfully grafted to the ESM via amidation reactions and confirmed using FT-IR, which demonstrated the distinctive peaks associated with Amide A (3275 cm−1), Amide B (2970 cm−1), Amide I (1630 cm−1), Amide II (1535 cm−1), CH2, CH3 groups, and Amide III (1250 cm−1) peaks. Confirmation of the incorporation of AgNP onto the stratified membrane was confirmed visually with SEM, qualitatively using FT-IR and also via changes in absorbance at 380 nm using UV-Vis spectrophotometry during a controlled release study for 72 h. The biocompatibility and cytotoxicity of the novel constructs were assessed using human dermal fibroblast (HDFa) and mouse dermal fibroblast (L929) cells and standard cell culture assays. Metabolic activity assessment (i.e., MTS assay), LDH-release profiles and Live/Dead staining demonstrated good attachment and spreading to the samples, and high cell viability following 3 days of culture. Interestingly, longer-term viability (>5 days), the ESM-PNIPAAm and ESM-PNIPAAm (AgNP) samples showed a greater and sustained cell viability profile. In summary, the modified and enhanced ESM constructs were successfully prepared and characterized in terms of their physical and mechanical profiles. AgNP were successfully loaded into the construct and demonstrated a desirable release profile dependent on temperature modulation. Fibroblasts cultured on the extracted ESM samples and ESM-PNIPAAm demonstrated high biocompatibility in terms of high cell attachment, spreading, viability and proliferation rates. As such, this work summarizes the development of an enhanced ESM-based construct which may be exploited as a clinical/therapeutic wound dressing as well as a possible application as a novel biomaterial scaffold for drug development. [ABSTRACT FROM AUTHOR]

The inclusion of physiologically active molecules into a naturally occurring polymer matrix can improve the degradation, absorption, and release profile of the drug, thus boosting the therapeutic impact and potentially even reducing the frequency of administration. The human body produces significant amounts of polysaccharide hyaluronic acid, which boasts exceptional biocompatibility, biodegradability, and one-of-a-kind physicochemical features. In this review, we will examine the clinical trials currently utilizing hyaluronic acid and address the bright future of this versatile polymer, as well as summarize the numerous applications of hyaluronic acid in drug delivery and immunomodulation. [ABSTRACT FROM AUTHOR]

Novel nanocomposite materials based on Fe3O4 magnetic nanoparticles (MNPs) coated with silica and covalently modified by [(3-triethoxysilyl)propyl]succinic acid–polyethylene glycol (PEG 3000) conjugate, which provides a high level of doxorubicin (Dox) loading, were obtained. The efficiency of Dox desorption from the surface of nanomaterials under the action of an alternating magnetic field (AMF) in acidic and neutral media was evaluated. Their high cytotoxicity against tumor cells, as well as the drug release upon application of AMF, which leads to an increase in the cytotoxic effect, was demonstrated. [ABSTRACT FROM AUTHOR]