Drug Delivery Carriers Research Articles

Diversity of extracellular vesicles derived from calli, cell culture and apoplastic fluid of tobacco

In recent years, there has been a growing interest in plant extracellular vesicles (pEVs) due to their immense potential for medical applications, particularly as carriers for drug delivery. To use the benefits of pEVs in the future, it is necessary to identify methods that facilitate their production in sufficient quantities while maintaining high quality. In this study, a comparative analysis of yields of tobacco pEV derived from apoplastic fluid, sterile calli, and suspension cultures, was performed to identify the most suitable plant material for vesicle isolation. Subsequent experiments focused on assessing the efficiency of small interfering RNA (siRNA) loading into callus-derived vesicles, employing various methods such as sonication, incubation, incubation supplemented with saponin, lipofection, and electroporation. Differences in loading efficiency among vesicles derived from apoplastic fluid, calli, and suspension cultures were observed. Moreover, our investigation extended to the presence of tobacco secondary metabolites, specifically anabasine and nicotine, within vesicles originating from three distinct tobacco sources. The outcomes of our study highlight variations not only in vesicle yields based on their source but also in their loadability and the presence of nicotine and anabasine. These findings contribute valuable insights into optimizing the production and application of pEVs for future medicinal purposes.

Enzyme-induced degradation of natural and artificial linear polyanions

Synthetic and natural polymers are widely used for constructing drug delivery systems. Biocompatibility, water solubility and non-toxicity make polymers a convenient matrix for encapsulation, delivery and release of bioactive compounds [1–6]. Coupling of a drug with a biodegraded polymer matrix is a promising way for a controlled drug delivery. Along this line, the degradation of the four polymers in the presence of two enzymes in aqueous solutions was investigated. The following polymers were used: natural polysaccharides, sodium alginate and sodium hyaluronate, artificial (modified) sodium carboxymethylcellulose and synthetic sodium polyacrylate (control); their degradation was caused by the addition of alginate lyase and hyaluronidase. The first enzyme only cleaved the specific alginate substrate and left three other intact. Contrastingly, the second enzyme degraded all three polysaccharides, including artificial carboxymethylcellulose, but did not degrade synthetic polyacrylate. The biodegradation of polymers was accompanied by decreasing the size of polymer particles in solution from 100-200 nm down to 20-30 nm; the latter are capable of removing from the body through the kidneys. The initial polysaccharides showed the negative surface charge in aqueous solution, which changed but retained negative after biodegradation. The initial and biodegraded polysaccharides demonstrated negligible cytotoxicity during long exposure period. The obtained results are valuable for the development of polymer carriers for drug encapsulation and delivery.

Macrophage membrane-encapsulated miRNA nanodelivery system for the treatment of hemophilic arthritis

Hemophilic arthritis (HA) is one of the most pathologically altered joint diseases. Specifically, periodic spontaneous hemorrhage-induced hyperinflammation of the synovium and irreversible destruction of the cartilage are the main mechanisms that profoundly affect the behavioral functioning and quality of life of patients. In this study, we isolated and characterized platelet-rich plasma-derived exosomes (PRP-exo). We performed microRNA (miRNA) sequencing and bioinformatics analysis on these exosomes to identify the most abundant miRNA, miR-451a. Following this, we developed an M@ZIF-8@miR nanotherapeutic system that utilizes nanoscale zeolitic imidazolate framework (ZIF) as a carrier for miRNA delivery, encapsulated within M2 membranes to enhance its anti-inflammatory effects. In vitro and in vivo studies demonstrated that M@ZIF-8@miR significantly reduced pro-inflammatory cytokines, controlled synovial inflammation, and achieved potent therapeutic efficacy by reducing joint damage. We suggest that the ability of M@ZIF-8@miR nanocomposites to inhibit pro-inflammatory cytokines, enhance cellular uptake, and exhibit good endosomal escape properties makes them promising carriers for the efficient delivery of therapeutic nucleic acid drugs. This approach delays joint degeneration and provides a promising combinatorial strategy for HA treatment.

Exploring the potential of plasma and adipose mesenchymal stem cell-derived extracellular vesicles as novel platforms for neuroinflammation therapy

Persistent reactive oxygen species (ROS) and neuroinflammation contribute to the onset and progression of neurodegenerative diseases, underscoring the need for targeted therapeutic strategies to mitigate these effects. Extracellular vesicles (EVs) show promise in drug delivery due to their biocompatibility, ability to cross biological barriers, and and specific interactions with cell and tissue receptors. In this study, we demonstrated that human plasma-derived EVs (pEVs) exhibit higher brain-targeting specificity, while adipose-derived mesenchymal stem cells EVs (ADMSC-EVs) offer regenerative and immunomodulatory properties. We further investigated the potential of these EVs as therapeutic carriers for brain-targeted drug delivery, using Donepezil (DNZ) as the model drug. DNZ, a cholinesterase inhibitor commonly used for Alzheimer's disease (AD), also has neuroprotective and anti-inflammatory properties. The size of EVs used ranged from 50 to 300 nm with a surface charge below −30 mV. Both formulations showed rapid cellular internalization, without toxicity, and the ability to cross the blood-brain barrier (BBB) in a zebrafish model. The have analyzed the anti-inflammatory and antioxidant actions of pEVs-DNZ and ADMSC-EVs-DNZ in the presence of lipopolysaccharide (LPS). ADMSC-EVs significantly reduced the inflammatory mediators released by HMC3 microglial cells while treatment with pEVs-DNZ and ADMSC-EVs-DNZ lowered both phagocytic activity and ROS levels in these cells. In vivo experiments using zebrafish larvae revealed that both EV formulations reduced microglial proliferation and exhibited antioxidant effects. Overall, this study highlights the potential of EVs loaded with DNZ as a novel approach for treating neuroinflammation underlying various neurodegenerative diseases.

Research Progress of Hyaluronic Acid-Coated Nanocarriers in Targeted Cancer Therapy.

Background: Hyaluronic acid (HA), as a critical ingredient of extracellular matrix (ECM) and synovial fluid, has attracted extensive attention in targeted tumor thearpy. The superiority of HA is reflected as its great biocompatibility, biodegradability and special binding ability to CD44 receptor. Moreover, CD44 receptor proteins are overexpressed in many kinds of tumor cells and cancer stem cells (CSCs). Therefore, HA is commonly used as ligands for the surface modification of versatile nanocarriers applied in various tumor therapy approaches. Methods: We reviewed a large amount of literature and summarized the unique properties of HA, the rationale for the use of HA as tumor-specific carrier for drug delivery, catabolism of HA coated nanocarriers and research achievements of frequently-used HA-modified organic and inorganic nanocarries. Results: We concluded the significant applications of HA coated nanocarriers in tumor Chemotherapy and chemoresistance, Combination therapy and Cancer theranostics. Conclusion: The application prospect of HA-coated nanocarriers will be more extensive for various targeting combination therapy and theranostics. was concluded so as to provide some potential thoughts for targeted tumor thearpy and even diagnosis.

Preparation, Characterization and Immune Activity of ViolaPhilippicaPolysaccharide PLGA Nanoparticles.

Recent pharmacological studies have demonstrated that Viola philippicapolysaccharide (VPP) exhibits a modulating effect on immune activity. However, its utilization has been hampered by its large particle size and complex spatial structure. Poly-lactic-co-glycolic acid copolymer (PLGA) is recognized as an effective drug delivery carrier, exhibiting excellent biochemical properties. In this experiment, VPP was encapsulated with PLGA to form Viola philippica polysaccharide PLGA nanoparticles (VPP-PLGA NPs). The morphological structure and immunomodulatory effects of VPP-PLGA NPs were evaluated. The particle size of VPP-PLGA NPs was reduced compared to VPP, and the optimal preparation conditions were as follows: the ratio of the organic phase to the internal aqueous phase was 8:1, the ratio of the external aqueous phase to the primary emulsion was 7:1, and the concentration of PLGA was 20 mg/mL. Additionally, VPP-PLGA NPs significantly increased the NO content, IL-4, and IFN-γ levels in RAW264.7 cells, as well as enhanced their phagocytic activity. Furthermore, VPP-PLGA NPs were found to increase NO content and IFN-γ secretion in bone marrow-derived dendritic cells (BMDCs). These findings suggest that VPP-PLGA NPs could enhance the immune activity and may be utilized as a VPP delivery system for inducing strong immune responses.

Synthesis and Characterization of Polyion Complex Micelles with Glycopolymer Shells for Drug Delivery Carriers.

Double hydrophilic diblock copolymers (G20A100 and G100A98), composed of non-charged poly(glycosyloxyethyl methacrylate) (PGEMA, G) and cationic poly((3-acrylamidopropyl)trimethylammonium chloride), were synthesized via reversible addition-fragementation chain transfer (RAFT) radical polymerization. Likewise, diblock copolymers (G20S80 and G100S78), composed of PGEMA and anionic poly(2-acrylamido-2-methylpropanesulfonate) were synthesized via RAFT. The subscripts in these abbreviations indicate the degree of polymerization (DP) of each block. Polyion complex (PIC) aggregates (G20A100/G20S80 and G100A98/G100S78) were formed through electrostatic interactions by combining oppositely charged diblock copolymers with matched DPs for charge neutralization. The hydrodynamic radii of the G20A100/G20S80 and G100A98/G100S78 PIC aggregates were 77.4 and 26.2 nm, respectively, with zeta potentials close to 0 mV. The G20A100/G20S80 PIC micelles tend to form intermicellar aggregates, resulting in an increase in the particle size over time. In contrast, G100A98/G100S78 PIC micelles exhibited colloidal stability with a constant spherical core-shell shape, which was unaffected by time. The morphology and stability of the PIC aggregates depend upon the DP ratio of PGEMA and oppositely charged polyelectrolyte blocks. Both G20A100/G20S80 and G100A98/G100S78 PIC aggregates dissociated above 0.8 M NaCl due to the screening effect of NaCl.

Advances in the application of live bacteria as vehicles for delivering antitumor drugs

Some bacteria can selectively colonize the tumor site and inhibit tumor growth, serving as ideal vehicles for delivering antitumor drugs. The system of delivering antitumor drugs with live bacteria as vehicles is characterized by good biocompatibility and precise targeting. However, the development of bacteria as drug delivery vehicles is limited by their own immunogenicity. In this paper, the selection of chassis bacteria, bacterial loading drug strategies, antitumor drug delivery applications and their limitations are elaborated in detail, and its future development direction is envisioned, with a view to providing a reference for the study of live bacteria as antitumor drug delivery carriers.

Oral and tumor-targeting mixed micelles based on pegylated biotin and chitosan-based conjugate for breast cancer treatment

Oral drug delivery with tumor-targeting treatment persists as a challenge. In this study, a mixed polymeric micelle (PM) delivery system was designed to overcome the barriers to oral administration for tumor-targeting delivery of paclitaxel (PTX) for breast cancer treatment. D-α-Tocopheryl polyethylene glycol 1000 succinate-modified carboxymethyl chitosan-rhein (TCR) conjugate and Biotin-polyethylene glycol 2000-Biotin (BPB) conjugate were mixed to form TCR-BPB PMs. The particle size and polydispersity index of optimized PTX-loaded TCR-BPB PMs (PTX/TCR-BPB PMs) was 195.90 ± 7.63 nm and 0.08 ± 0.00, with a drug-loading capacity of 41.94 ± 2.47 %. In simulated gastroenteric fluid and blood environments, the PMs presented a sustained-release manner. PTX/TCR-BPB PMs were taken up by Caco-2 and 4T1 cells and displayed strong cytotoxicity in a time- and concentration-dependent manner. PTX/TCR-BPB PMs significantly improved intestinal absorption of PTX. The pharmacokinetics, tissue distribution, and in vivo imaging indicated that PTX/TCR-BPB PMs could enhance oral bioavailability of PTX, prolong the retention time of PTX in the blood, and enhance PTX tumor-targeting ability. PTX/TCR-BPB PMs enhance the antitumor efficacy of PTX and reduce its toxicity in normal organs. Therefore, TCR-BPB PMs are expected to serve as delivery carriers for the oral and tumor-targeting delivery of hydrophobic antitumor drugs.

Marine Cyanobacteria-Assisted Metallic Nanoparticles: A Review on Anticancer Activity and Mechanism of Action

Marine cyanobacteria, known as blue-green algae, are ancient microorganisms with oxygenic photosynthetic capability. They have diverse biochemical capabilities, including production of bioactive secondary metabolites. We studied the anti-cancer properties of cyanobacterial nanoparticles through various literatures. We focused on mechanistic studies of the anticancer properties of metal and metal oxide nanoparticles. Our research gathered information from patent databases, conference abstracts, publications, and news releases, as well as PubMed searches for peer-reviewed articles and Google searches for gray literature. We used strict criteria for selecting sources, and our search ended on 30 October, 2022. Metal nanoparticles, such as gold and silver, have unique physicochemical properties, making them suitable for therapeutic applications in nanomedicine. Cyanobacteria-assisted synthesis is environmentally sustainable and results in mild reaction conditions and minimal toxic byproducts. These nanoparticles have potential applications in cancer therapy, including drug delivery systems and targeted therapies. This study further explored the mechanistic aspects of cancer development, emphasising the role of genetic mutations, uncontrolled cell growth, and metastasis. Cyanobacterial biogenic nanoparticles demonstrate cytotoxicity, apoptosis induction, ROS generation, and immunomodulation, contributing to their anticancer efficacy. Additionally, these nanoparticles serve as carriers for drug delivery, enabling the targeted and controlled release of therapeutic agents. The review ends by emphasising how crucial it is to comprehend how cyanobacteria extract assists metallic nanoparticles. Cyanobacterial biogenic synthesis using microemulsion synthesis methods, UV-initiated photoreduction, microwave assistance, and polymer/polysaccharide-mediated approaches was investigated. The field of marine cyanobacteria, biogenic metal nanoparticles, and their anticancer potential is dynamic and has important implications for future therapeutic approaches.

Pectin/Alginate bio-nanocomposite hydrogel beads based on in-situ formed layered double hydroxide in the presence of Mentha extract: Antibacterial carrier for potential pH-responsive targeted anti-cancer drug delivery

This research presents the creation of novel pH-responsive drug delivery carriers with potential applications in cancer treatment. The study involved the Mentha Extract (ME) for the in-situ synthesis of Layered Double Hydroxide (LDH) bio nanoparticles (LDH-ME NPs). These NPs were incorporated into a biopolymeric hybrid formulation containing Pectin and Alginate to produce bio-nanocomposite hydrogel beads. The morphology and chemical composition were assessed and confirmed through various techniques. Doxorubicin (DOX) was employed as a representative anti-cancer medication to investigate the controlled drug release properties of the newly developed hydrogel beads (loading capacity: ∼92 %). In vitro experiments revealed that the drug release pattern was significantly regulated in response to pH levels (with a higher drug release rate at pH 7.4, about 89 %). The assessment for antibacterial properties validated the effective antibacterial performance of the hydrogel beads toward S. aureus and E. coli with inhibition zones about 20 mm and 14 mm, respectively. MTT assay indicated a high level of cytocompatibility with HT-29 cells (cell viability exceeding 95 %) for the blank bio-nanocomposite hydrogel beads. Conversely, bio-nanocomposite hydrogel beads loaded with DOX exhibited notable cytotoxicity (∼13 % cell viability in 15.6 µg/mL) against HT-29 cells. These findings recommend the current bio-nanocomposite as a promising bio-platform with superior antibacterial and anti-cancer properties.

Efficient Loading into and Controlled Release of Lipophilic Compound from Liposomes by Using Cyclodextrin as Novel Trapping Agent.

Lipid bilayer vesicles, liposomes are representative drug delivery carriers. High encapsulation efficiency and release control of drugs are essential for clinical application of liposomes. For efficient drug loading into liposomes, remote loading method using driving force like transmembrane gradients of pH and ions are utilized. Ions are called as "trapping agents," which are also critical for the controlled release of drugs loaded into liposomes inside. It is difficult to apply ions as trapping agents to various drugs because of limited physicochemical compatibility between drugs and ions. Cyclodextrins (CDs) with hydrophobic cavity can make inclusion complexes with various hydrophobic compounds. Therefore, we aimed to evaluate the potential of CDs as a novel trapping agent using sulfobutylether-β-cyclodextrin (SBE-β-CD) and ibuprofen (IB), a weak acid hydrophobic drug. Encapsulation efficiency of IB in liposomes with pH gradient was approximately 27%, and it was enhanced by intraliposomal SBE-β-CD inclusion in addition to pH gradient, which was SBE-β-CD concentration-dependent. In liposomes with pH gradient, a large fraction of IB was released in a short time. This early-stage rapid IB release was significantly suppressed by the inclusion of SBE-β-CD inside liposomes. Thus, novel remote loading technology by intraliposomal SBE-β-CD enabled the efficient encapsulation of the hydrophobic drug into the aqueous phase of liposomes as well as their controlled release. This technology should be applied to various drugs that can be included into CDs in order to enhance their therapeutic benefits.

ADVANCING TOPICAL POSACONAZOLE DELIVERY: BOX BEHNKEN DESIGN MICROSPONGE HYDROGEL OPTIMIZATION AND EXTENSIVE IN VIVO INVESTIGATION

Objective: The primary aim of this study was to develop a novel hydrogel formulation containing Posaconazole (PCZ) encapsulated within microsponges. Furthermore, the study aimed to assess the permeation properties of this formulation in vivo using a mouse model. Methods: To achieve this aim, a series of seventeen trials were conducted using the Box Behnken Design methodology. These trials were designed to optimize the production of PCZ Microsponges (PCZ MS), which were subsequently incorporated into a hydrogel matrix. Skin permeation studies were then performed to evaluate the ability of the PCZ microsponge-based hydrogel to deliver the drug across the skin barrier. These studies involved comparison with a standard hydrogel formulation lacking microsponges. Results: This study assessed the efficacy of microsponge gel formulation PM-3 for drug entrapment, yield, and sustained release compared to a conventional gel. PM-3 displayed the highest entrapment efficiency of 98.5% and a yield of 95.62%, indicating a direct correlation with the 1:1 drug-polymer ratio. Moreover, PM-3 exhibited sustained drug release over 12 h, releasing 83.82% of PCZ compared to 65.31% with the normal gel, suggesting its potential for prolonged therapeutic action. These findings underscore the promise of microsponge-based hydrogels, like PM-3, in enhancing therapeutic outcomes through sustained drug release, warranting further exploration for clinical applications. Conclusion: The findings of this study highlight the promising potential of microsponge-based hydrogels as effective carriers for localized drug delivery, particularly in the context of treating skin fungal infections.

PH-Responsive Deacetylated Sphingan WL Gum-Based Microgels for the Oral Delivery of Ciprofloxacin Hydrochloride.

Sphingan WL gum (WL) is an extracellular polysaccharide with a carboxyl group produced by Sphingomonas sp. WG. Recently, we have successfully obtained deacetylated WL (DWL) with good water solubility by alkaline treatment. In this study, a DWL-based microgel (named DWLM) with semi-interpenetrating network structure was constructed for the first time and used to deliver the oral drug ciprofloxacin hydrochloride (CIP). DLS results suggested that DWLM had a dual response to pH and temperature. The in vitro cumulative drug release curves showed that the amount of CIP released from the microgel was higher at pH 6.8 than that at pH 3.0. Biocompatibility assessments using HEK293T showed that cell viability was 75.9 ± 1.7% at the DWLM-CIP concentration of 4 mg/mL. While, the cell viability of CIP at the same concentration was only 54.9 ± 1.0%, indicating that DWLM-CIP has good biocompatibility. Antimicrobial performance tests revealed that DWLM-CIP at a concentration of 1 mg/mL could effectively inhibit the growth of Escherichia coli for up to 4 days. When the concentration of DWLM-CIP reached 4 mg/mL, the growth of Staphylococcus aureus was effectively suppressed for up to 3 days, demonstrating the long-lasting antimicrobial efficacy of DWLM-CIP. All of these results indicate that DWL-based microgels have great potential as oral drug delivery carriers.

Jade powder/PLGA composite microspheres for improved performance as potential bone repair drug carrier

Poly (lactic-co-glycolic acid) (PLGA) has been widely used as drug delivery carrier or scaffold for bone repair due to its good biocompatibility, biodegradability, and degradation rate controllability. However, defects, like acidic degradation by-products, are associated with PLGA and restrict its practical applications. Jade powder, leftover from jade polishing process, is a natural material rich in elements of Ca, Si, and Mg while biocompatible and antibacterial. Herein, jade powder/PLGA composite microspheres with different mass ratios were prepared by emulsion solvent evaporation method under the optimized conditions. Characterization from SEM, EDS, FTIR, and surface water contact angle measurements indicated jade powder was successfully combined with PLGA and improved the surface wettability of the microspheres. Moreover, it was proved, through in vitro simulated body fluid test as well as adipose stem cell osteogenesis analysis, that jade powder addition enhanced the pH buffering capacity of the composite microsphere for simulated body fluid, and promoted the in vitro osteogenic activity of adipose stem cells at a certain amount. This study provides new ideas to employ jade powder, a natural material otherwise thrown away as solid waste, for improvement on PLGA performance in bone repair or potentially other biomedical fields.

Camel milk-derived exosomes as novel nanocarriers for curcumin delivery in lung cancer

Cancer remains a leading cause of mortality, with non-small cell lung cancer (NSCLC) being a primary contributor to cancer-related deaths. Traditional treatment strategies such as chemotherapy, radiation, and hormone therapy often present challenges, including severe side effects, drug resistance, and toxicity. Recent advancements in nanotechnology aim to enhance the effectiveness of cancer therapies by targeting drugs selectively and specifically to tumor cells. Among these innovations, exosomes, or small extracellular vesicles (EVs), have emerged as promising carriers for drug delivery due to their natural origin and ability to encapsulate both small molecules and biologics. This study explores the use of exosomes derived from camel milk in Hail, Saudi Arabia, as a vehicle for delivering curcumin (CUR), a polyphenol with known chemopreventive properties but limited bioavailability. Camel milk was processed to isolate exosomes through differential centrifugation, followed by characterization using dynamic light scattering, zeta potential measurements, and Western blot analysis to confirm exosomal markers. The encapsulation of CUR into camel milk-derived exosomes demonstrated a 20% loading efficiency as analyzed by UPLC. In vitro antiproliferative assays revealed that the exosomal formulation of CUR (ExoCUR) significantly enhanced cytotoxicity against drug -sensitive (A549) and taxol-resistant (A549TR) lung cancer cells compared to free CUR. Molecular docking studies and molecular dynamics simulations indicated that CUR has a strong binding affinity for the epidermal growth factor receptor (EGFR), comparable to the established drug gefitinib. Furthermore, CUR effectively downregulated EGFR and STAT3 expression in cancer cells, suggesting its potential to disrupt key signaling pathways involved in tumor progression. Our findings highlight the potential of camel milk-derived exosomes as an effective and biocompatible delivery system for CUR, offering a promising strategy to overcome the limitations of current cancer therapies and enhance the therapeutic efficacy of chemopreventive agents.

A new insight into the mechanism of loading of Granisetron, Naltrexone and Risperidone in poly(ortho ester) and poly (lactic-co-glycolic acid) as the controlled release drug delivery systems using a computational molecular approach

Owing to the good biocompatibility, bioavailability, biodegradability, and low toxicity of polymeric nanoparticles, considerable research interest has been generated. These polymeric carriers enhance the therapeutic index and improve controlled drug release. In this study, molecular dynamics (MD) simulation of six designed systems were conducted to compare poly(ortho ester) (POE) and poly (lactic-co-glycolic acid) (PLGA) polymeric nanoparticles as carriers and delivery systems for three drugs: Granisetron, Naltrexone, and Risperidone. These drugs are FDA-approved under the brand name SUSTOL (Granisetron for anti-nausea and vomiting post-heavy chemotherapy), VIVITROL (Naltrexone for managing alcohol or opioid use disorder), and RISPERDAL CONSTA (Risperidone for treating schizophrenia). Various parameters, such as interaction energy, radius of gyration (Rg), solvent accessible surface area (SASA), distance, hydrogen bond, radial distribution function (RDF), and root mean square fluctuation (RMSF), were investigated. The MD simulations show good consistency with FDA-approved data, clearly illustrate why PLGA is suitable for NAL and RIS, and POE for GRS, as carriers in drug delivery. The findings, detailing mechanisms of polymer-drug interactions, have potential applications in (i) manufacturing and production of novel sustained-release drugs and biopolymers, (ii) identifying suitable patterns, and (iii) rationally designing new controlled-release drugs based on future artificial intelligence methods.

Biowaste Transformation to Functional Materials: Structural Properties, Extraction Methods, Applications, and Challenges of Silk Sericin

AbstractThis review underscores the novelty of silk sericin, often regarded as a byproduct in silk production. Comprising approximately 30% of silk, sericin possesses valuable properties that have been largely overlooked in favor of silk fibroin. This work focuses on innovative extraction methods to convert sericin, typically considered waste, into a valuable resource. By examining these extraction techniques alongside diverse applications, the review aims to enhance the recognition and utilization of silk sericin in research and industry. Various extraction processes where the traditional methods, and some new techniques, are all discussed. In detail, the advantages, limitations, and strategy optimization associated with each extraction method are highlighted. For instance, silk sericin has shown promise as a wound treatment agent, a scaffold for tissue engineering, a carrier for drug delivery, and a biomaterial for regenerative medicine in the field of biomedical science due to its biocompatibility, biodegradability, and nontoxicity. Additionally, it also finds application in the cosmetic industry, where it is used in skincare products due to its moisturizing, antioxidant, and antiaging properties. Eventually, the challenges, limitations, and prospects of silk sericin are intensively discussed. This comprehensive review is expected to serve the growing body of knowledge surrounding silk sericin and foster further research and development of silk sericin‐related fields.

PH-responsive magnetic nanocarrier based on hyaluronic acid-folic acid conjugated Fe3O4 nanoparticles for controlled delivery of imatinib: Isotherms, kinetics, and thermodynamics studies

A novel pH-responsive magnetic nanocarrier was synthesized with hyaluronic acid/folic acid conjugated magnetic nanoparticles and used as a drug carrier for imatinib drug delivery. Magnetic nanoparticles were surface modified with (3-glycidyloxypropyl) trimethoxysilane. Grafting of hyaluronic acid/folic acid on these magnetic nanoparticles was characterized by Fourier-transform infrared spectroscopy, X-ray diffraction, Field emission scanning electron microscopy, thermogravimetric analysis, and vibrating sample magnetometer. The effect of adsorption parameters such as pH, initial concentration, contact time, and adsorbent dosage was examined. The pseudo-second-order model best described the kinetic data, while the Langmuir model best described the isotherm data, indicating physico-sorption and monolayer imatinib adsorption, respectively. Also, thermodynamic experiments showed that the uptake of the drug by the magnetic adsorbent was endothermic and spontaneous. The maximum sorption capacity of unmodified magnetic nanoparticle for imatinib was 6.38 mg/g and for modified magnetic nanoparticles, it was 16.56 mg/g. Imatinib as an anticancer drug, was loaded and the release curve was investigated at pH 5.6 and 7.4 for 6 h. At acidic fluid, the amount of imatinib released increased to 63.01 % compared to physiological fluid with 26.04 % drug release.

Solvent Choice during Flow Assembly of Photocross-Linked Single-Chain Nanoparticles and Micelles Affects Cellular Uptake.

Polymeric micelles have widely been used as drug delivery carriers, and recently, single-chain nanoparticles (SCNPs) emerged as potential, smaller-sized, alternatives. In this work, we are comparing both NPs side by side and evaluate their ability to be internalized by breast cancer cells (MCF-7) and macrophages (RAW 264.7). To be able to generate these NPs on demand, the polymers were assembled by flow, followed by the stabilization of the structures by photocross-linking using blue light. The central aim of this work is to evaluate how the type of solvent affects self-assembly and ultimately the structure of the final NP. Therefore, a library of copolymers with different sequences, including block copolymers (AB, ABA, BAB), and statistical copolymers (rAB and rAC) was synthesized using PET-RAFT with A denoting poly(ethylene glycol) methyl ether acrylate (PEGMEA), B as 2-hydroxyethyl acrylate (HEA), and C as 4-hydroxybutyl acrylate (HBA). The polymers were conjugated with a quinoline derivative to enable the formation of cross-linked structures by photocross-linking during flow assembly. Using water as the dispersant for photocross-linking led to the preassembly of these amphiphilic polymers into compact SCNPs and cross-linked micelles, resulting in a quick photoreaction. In contrast, acetonitrile led to fully dissolved polymers but a low rate of the photoreaction. These intramolecularly cross-linked polymers were then placed in water to result in more dynamic micelles and looser SCNPs. Small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), and size exclusion chromatography (SEC) coupled with a viscosity detector show that cross-linking in acetonitrile results in better-defined NPs with a shell rich in PEGMEA. Cross-linking in acetonitrile led to NPs with significantly higher cellular uptake. Interestingly, passive transport was identified as the main pathway for the delivery of our NPs on MCF-7 cells, confirmed by the uptake of NPs on cells treated with inhibitors and by red blood cells. This work underscored the importance of the polymer precursor's structure and the choice of solvent during intramolecular cross-linking in determining the drug delivery efficiency and biological behavior of SCNPs.