Cell Membrane Fragment-Wrapped Parenteral Nanoemulsions: A New Drug Delivery Tool to Target Gliomas.

Poor prognosis in high-grade gliomas is mainly due to fatal relapse after surgical resection in the absence of efficient chemotherapy, which is severely hampered by the blood-brain barrier. However, the leaky blood-brain-tumour barrier forms upon tumour growth and vascularization, allowing targeted nanocarrier-mediated drug delivery. The homotypic targeting ability of cell-membrane fragments obtained from cancer cells means that these fragments can be exploited to this aim. In this experimental work, injectable nanoemulsions, which have a long history of safe clinic usage, have been wrapped in glioma-cell membrane fragments via co-extrusion to give targeted, homogeneously sized, sterile formulations. These systems were then loaded with three different chemotherapeutics, in the form of hydrophobic ion pairs that can be released into the target site thanks to interactions with physiological components. The numerous assays performed in two-dimensional (2D) and three-dimensional (3D) cell models demonstrate that the proposed approach is a versatile drug-delivery platform with chemo-tactic properties towards glioma cells, with adhesive interactions between the target cell and the cell membrane fragments most likely being responsible for the effect. This approach's promising translational perspectives towards personalized nanomedicine mean that further in vivo studies are foreseen for the future.

Revolutionizing Knee Osteoarthritis Treatment: Innovative Self-Nano-Emulsifying Polyethylene Glycol Organogel of Curcumin for Effective Topical Delivery.

In the current study, self-nano-emulsifying (SNE) physically cross-linked polyethylene glycol (PEG) organogel (SNE-POG) as an innovative hybrid system was fabricated for topical delivery of water-insoluble and unstable bioactive compound curcumin (CUR). Response surface methodology (RSM) based on Optimal Design was utilized to evaluate the formulation factors. Solid fiber mechanism with homogenization was used to prepare formulations. Pharmaceutical evaluation including rheological and texture analysis, their mathematical correlations besides physical and chemical stability experiments, DSC study, in vitro release, skin permeation behavior, and clinical evaluation were carried out to characterize and optimize the SNE-OGs. PEG 4000 as the main organogelator, Poloxamer 188 (Plx188) and Ethyl Cellulose (EC) as co-gelator/nanoemulsifier agents, and PEG 400 and glycerin as solvent/co-emulsifier agents could generate SNE-POGs in PS range of 356 to 1410 nm that indicated organic base percentage and PEG 4000 were the most detrimental variables. The optimized OG maintained CUR stable in room and accelerated temperatures and could release CUR sustainably up to 72 h achieving high flux of CUR through guinea pig skin. A double-blind clinical trial confirmed that pain scores, stiffness, and difficulty with physical function were remarkably diminished at the end of 8 weeks compared to the placebo (71.68% vs. 7.03%, 62.40% vs. 21.44%, and 45.54% vs. 8.66%, respectively) indicating very high efficiency of system for treating knee osteoarthritis. SNE-POGs show great potential as a new topical drug delivery system for water-insoluble and unstable drugs like CUR that could offer a safe and effective alternative to conventional topical drug delivery system.

Theory of nanostructured sensors integrated in/on microneedles for diagnostics and therapy.

Efficient real-time diagnostics and on-demand drug delivery are essential components in modern healthcare, especially for managing chronic diseases. The lack of a rapid and effective sensing and therapeutic system can result in analyte level deviations, leading to severe complications. Minimally invasive microneedle (MN)-based patches integrating nanostructures (NSs) in their volume or on their surface have emerged as a biocompatible technology for delay-free analyte sensing and therapy. However, a quantitative relationship for the signal response in NS-assisted reactions remains elusive. Existing generalized formalisms are derived for in-vitro applications, raising questions about their direct applicability to in-situ wearable sensors. In this study, we apply the reaction-diffusion theory to establish a generalized physics-guided framework for NS-in-MN platforms in wearable applications. The model relates the signal response to analyte concentration, incorporating geometric, physical, and catalytic platform properties. Approximating the model under NS (binding or catalytic) and environmental (mass transport) limitations, we validate it against numerical simulations and various experimental results from diverse conditions - analyte sensing (glucose, lactic acid, pyocyanin, miRNA, etc.) in artificial and in-vivo environments (humans, mice, pigs, plants, etc.) through electrochemical and optical/colorimetric, enzymatic and non-enzymatic platforms. The results plotted in the scaled response show that (a) NS-limited platforms exhibit a linear dependence, (b) Mass transport-limited platforms saturate to 1, (c) a one-to-one mapping against traditional sensitivity plots unifies the scattered data points reported in literature. The universality of the model provides insightful perspectives for the design and optimization of MN-based sensing technologies, with potential extensions to dissolvable MNs as part of analyte-responsive closed-loop therapeutic applications.

Methods, Mechanisms, and Application Prospects for Enhancing Extracellular Vesicle Uptake.

Extracellular vesicles (EVs) are considered to be a new generation of bioinspired nanoscale drug delivery systems due to their low immunogenicity, natural functionality, and excellent biocompatibility. However, limitations such as low uptake efficiency, insufficient production, and inhomogeneous performance undermine their potential. To address these issues, numerous researchers have put forward various methods and applications for enhancing EV uptake in recent decades. In this review, we introduce various methods for the cellular uptake of EVs and summarize recent advances on the methods and mechanisms for enhancing EV uptake. In addition, we provide further understanding regarding enhancing EV uptake and put forward prospects and challenges for the development of EV-based therapy in the future.

A Microfluidics-Assisted Double-Barreled Nanobioconjugate Synthesis Introducing Aprotinin as a New Moonlight Nanocarrier Protein: Tested toward Physiologically Relevant 3D-Spheroid Models.

Proteins are promising substances for introducing new drug carriers with efficient blood circulation due to low possibilities of clearance by macrophages. However, such natural biopolymers have highly sophisticated molecular structures, preventing them from being assembled into nanoplatforms with manipulable payload release profiles. Here, we report a novel anticancer nanodrug carrier moonlighting protein, Aprotinin, to be used as a newly identified carrier for cytotoxic drugs. The Aprotinin-Doxorubicin (Apr-Dox) nanobioconjugate was prepared via a single-step microfluidics coflow mixing technique, a feasible and simple way to synthesize a carrier-based drug design with a double-barreled approach that can release and actuate two therapeutic agents simultaneously, i.e., Apr-Dox in 1:11 ratio (the antimetastatic carrier drug aprotinin and the chemotherapeutic drug DOX). With a significant stimuli-sensitive (i.e., pH) drug release ability, this nanobioconjugate achieves superior bioperformances, including high cellular uptake, efficient tumor penetration, and accumulation into the acidic tumor microenvironment, besides inhibiting further tumor growth by halting the urokinase plasminogen activator (uPA) involved in metastasis and tumor progression. Distinctly, in healthy human umbilical vein endothelial (HUVEC) cells, drastically lower cellular uptake of nanobioconjugates has been observed and validated compared to the anticancer agent Dox. Our findings demonstrate an enhanced cellular internalization of nanobioconjugates toward breast cancer, prostate cancer, and lung cancer both in vitro and in physiologically relevant biological 3D-spheroid models. Consequently, the designed nanobioconjugate shows a high potential for targeted drug delivery via a natural and biocompatible moonlighting protein, thus opening a new avenue for proving aprotinin in cancer therapy as both an antimetastatic and a drug-carrying agent.

Surface engineered nanodiamonds: mechanistic intervention in biomedical applications for diagnosis and treatment of cancer.

In terms of biomedical tools, nanodiamonds (ND) are a more recent innovation. Their size typically ranges between 4 to 100 nm. ND are produced via a variety of methods and are known for their physical toughness, durability, and chemical stability. Studies have revealed that surface modifications and functionalization have a significant influence on the optical and electrical properties of the nanomaterial. Consequently, surface functional groups of NDs have applications in a variety of domains, including drug administration, gene delivery, immunotherapy for cancer treatment, and bio-imaging to diagnose cancer. Additionally, their biocompatibility is a critical requisite for theirin vivoandin vitrointerventions. This review delves into these aspects and focuses on the recent advances in surface modification strategies of NDs for various biomedical applications surrounding cancer diagnosis and treatment. Furthermore, the prognosis of its clinical translation has also been discussed.

Milk-Derived Extracellular Vesicles: Biomedical Applications, Current Challenges, and Future Perspectives.

Extracellular vesicles (EVs) are nano to-micrometer-sized sacs that are released by almost all animal and plant cells and act as intercellular communicators by transferring their cargos between the source and target cells. As a safe and scalable alternative to conditioned medium-derived EVs, milk-derived EVs (miEVs) have recently gained a great deal of popularity. Numerous studies have shown that miEVs have intrinsic therapeutic actions that can treat diseases and enhance human health. Additionally, they can be used as natural drug carriers and novel classes of biomarkers. However, due to the complexity of the milk, the successful translation of miEVs from benchtop to bedside still faces several unfilled gaps, especially a lack of standardized protocols for the isolation of high-purity miEVs. In this work, by comprehensively reviewing the bovine miEVs studies, we provide an overview of current knowledge and research on miEVs while highlighting their challenges and enormous promise as a novel class of theranostics. It is hoped that this study will pave the way for clinical applications of miEVs by addressing their challenges and opportunities.

Transmucosal Delivery of Peptides and Proteins Through Nanofibers: Current Status and Emerging Developments.

Advancements in recombinant DNA technology have made proteins and peptides available for diagnostic and therapeutic applications, but their effectiveness when taken orally leads to poor patient compliance, requiring clinical administration. Among the alternative routes, transmucosal delivery has the advantage of being noninvasive and bypassing hepato-gastrointestinal clearance. Various mucosal routes-buccal, nasal, pulmonary, rectal, and vaginal-have been explored for delivering these macromolecules. Nanofibers, due to their unique properties like high surface-area-to-volume ratio, mechanical strength, and improved encapsulation efficiency, serve as promising carriers for proteins and peptides. These nanofibers can be tailored for quick dissolution, controlled release, enhanced encapsulation, targeted delivery, and improved bioavailability, offering superior pharmaceutical and pharmacokinetic performance compared to conventional methods. This leads to reduced dosages, fewer side effects, and enhanced patient compliance. Hence, nanofibers hold tremendous potential for protein/peptide delivery, especially through mucosal routes. This review focuses on the therapeutic application of proteins and peptides, challenges faced in their conventional delivery, techniques for fabricating different types of nanofibers and, various nanofiber-based dosage forms, and factors influencing nanofiber generation. Insights pertaining to the precise selection of materials used for fabricating nanofibers and regulatory aspects have been covered. Case studies wherein the use of specific protein/peptide-loaded nanofibers and delivered via oral/vaginal/nasal mucosa for diagnostic/therapeutic use and related preclinical and clinical studies conducted have been included in this review.

Herbal Theranostics: Controlled, Targeted Delivery and Imaging of Herbal Molecules.

Modern medicine relies on a small number of key biologics, which can be found in nature but require further characterization and purification before they can be used. Since the herbal remedy is given through a dated and ineffective method of drug administration, its effectiveness is diminished. The novel form of medicine delivery has the potential to increase the effectiveness of herbal substances while decreasing their side effects. This is the main idea behind utilising different ways of drug delivery in herbal treatments. Several benefits arise from novel formulations of herbal compounds as compared to their conventional counterparts. These include enhanced penetrating ability into tissues, constant delivery of effective doses, and resistance to physical and chemical degradation. Controlled and targeted delivery that include herbal components allow for more traditional dosing while simultaneously increasing their efficacy. Enhancing the biodistribution and target site accumulation of systemically administered herbal medicines is the goal of nanomedicine formulations. The field of nanotheranostics has made significant advancements in the development of herbal compounds by combining diagnostic and therapeutic functions on a single nanoscale platform. It is critically important to create a theranostic nanoplatform that is derived from plants and is intrinsically "all-in-one" for single molecules. In addition to examining the mechanistic approach to nanoparticle synthesis, this review highlights the therapeutic effects of nanoscale phytochemical delivery systems. Furthermore, we have evaluated the scope for future advancements in this field, discussed several nanoparticles that have been developed recently for herbal imaging, and provided experimental evidence that supports their usage.

Minoxidil Nanosuspension-Loaded Dissolved Microneedles for Hair Regrowth.

Minoxidil (MIN) is used topically to treat alopecia. However, its low absorption limits its use, warranting a new strategy to enhance its delivery into skin layers. The objective of this study was to evaluate the dermal delivery of MIN by utilizing dissolved microneedles (MNs) loaded with MIN nanosuspension (MIN-NS) for hair regrowth. MIN-NS was prepared by the solvent-antisolvent precipitation technique. The particle size of MIN-NS was 226.7 ± 9.3 nm with a polydispersity index of 0.29 ± 0.17 and a zeta potential of -29.97 ± 1.23 mV. An optimized formulation of MIN-NS was selected, freeze-dried, and loaded into MNs fabricated with sodium carboxymethyl cellulose (Na CMC) polymeric solutions (MIN-NS-loaded MNs). MNs were evaluated for morphology, dissolution rate, skin insertion, drug content, mechanical properties, ex vivo permeation, in vivo, and stability studies. MNs, prepared with 14% Na CMC, were able to withstand a compression force of 32 N for 30 s, penetrate Parafilm M® sheet at a depth of 374-504 µm, and dissolve completely in the skin within 30 min with MIN %recovery of 95.1 ± 6.5%. The release of MIN from MIN-NS-loaded MNs was controlled for 24 h. MIN-NS-loaded MNs were able to maintain their mechanical properties and chemical stability for 4 weeks, when kept at different storage conditions. The in vivo study of the freeze-dried MIN-NS and MIN-NS-loaded MNs proved hair regrowth on rat skin after 11 and 7 days, respectively. These results showed that MIN-NS-loaded MNs could potentially improve the dermal delivery of MIN through the skin to treat alopecia.

Engineered Extracellular Vesicles in Chronic Kidney Diseases: A Comprehensive Review.

Chronic kidney diseases (CKD) present a formidable global health challenge, characterized by a deficiency of effective treatment options. Extracellular vesicles (EVs), recognized as multifunctional drug delivery systems in biomedicine, have gained accumulative interest. Specifically, engineered EVs have emerged as a promising therapeutic approach for targeted drug delivery, potentially addressing the complexities of CKD management. In this review, we systematically dissect EVs, elucidating their classification, biogenesis, composition, and cargo molecules. Furthermore, we explore techniques for EV engineering and strategies for their precise renal delivery, focusing on cargo loading and transportation, providing a comprehensive perspective. Moreover, this review also discusses and summarizes the diverse therapeutic applications of engineered EVs in CKD, emphasizing their anti-inflammatory, immunomodulatory, renoprotective, and tissue-regenerating effects. It critically evaluates the challenges and limitations in translating EV therapies from laboratory settings to clinical applications, while outlining future prospects and emerging trends.

Spatiotemporal modeling of nano-delivered chemotherapeutics for synergistic microwave ablation cancer therapy.

BACKGROUND AND OBJECTIVE: The effectiveness of current microwave ablation (MWA) therapies is limited. Administration of thermosensitive liposomes (TSLs) which release drugs in response to heat has presented a significant potential for enhancing the efficacy of thermal ablation treatment, and the benefits of targeted drug delivery. However, a complete knowledge of the mechanobiological processes underlying the drug release process, especially the intravascular drug release mechanism and its distribution in response to MWA needs to be improved. Multiscale computational-based modeling frameworks, integrating different biophysical phenomena, have recently emerged as promising tools to decipher the mechanobiological events in combo therapies. The present study aims to develop a novel multiscale computational model of TSLs delivery following MWA implantation. METHODS: Due to the complex interplay between the heating procedure and the drug concentration maps, a computational model is developed to determine the intravascular release of doxorubicin from TSL, its transvascular transport into the interstitium, transport in the interstitium, and cell uptake. Computational models can estimate the interplays among liposome and drug properties, tumor perfusion, and heating regimen to examine the impact of essential parameters and to optimize a targeted drug delivery platform. RESULTS: Results indicated that the synergy of TSLs with MWA allows more localized drug delivery with lower side effects. The drug release rate and tumor permeability play crucial roles in the efficacy of TSLs during MWA treatment. The computational model predicted an unencapsulated drug lime around the ablated zone, which can destroy more cancer cells compared to MWA alone by 40%. Administration of TSLs with a high release rate capacity can improve the percentage of killed cancer cells by 24%. Since the heating duration in MWA is less than 15 min, the presented combination therapy showed better performance for highly permeable tumors. CONCLUSION: This study highlights the potential of the proposed computational framework to address complex and realistic scenarios in cancer treatment, which can serve as the future research foundation, including advancements in nanomedicine and optimizing the pair of TSL and MWA for both preclinical and clinical studies. The present model could be as a valuable tool for patient-specific calibration of essential parameters.

Extracellular Vesicles: A New Star for Gene Drug Delivery.

Recently, gene therapy has become a subject of considerable research and has been widely evaluated in various disease models. Though it is considered as a stand-alone agent for COVID-19 vaccination, gene therapy is still suffering from the following drawbacks during its translation from the bench to the bedside: the high sensitivity of exogenous nucleic acids to enzymatic degradation; the severe side effects induced either by exogenous nucleic acids or components in the formulation; and the difficulty to cross the barriers before reaching the therapeutic target. Therefore, for the successful application of gene therapy, a safe and reliable transport vector is urgently needed. Extracellular vesicles (EVs) are the ideal candidate for the delivery of gene drugs owing to their low immunogenicity, good biocompatibility and low toxicity. To better understand the properties of EVs and their advantages as gene drug delivery vehicles, this review covers from the origin of EVs to the methods of EVs generation, as well as the common methods of isolation and purification in research, with their pros and cons discussed. Meanwhile, the engineering of EVs for gene drugs is also highlighted. In addition, this paper also presents the progress in the EVs-mediated delivery of microRNAs, small interfering RNAs, messenger RNAs, plasmids, and antisense oligonucleotides. We believe this review will provide a theoretical basis for the development of gene drugs.

A Hollow Microneedle Equipped with a Micropillar for Improved Needle Insertion and Injection of Drug Solution.

PURPOSE: Hollow-type microneedles (hMNs) are a promising device for the effective administration of drugs into intradermal sites. Complete insertion of the needle into the skin and administration of the drug solution without leakage must be achieved to obtain bioavailability or a constant effect. In the present study, several types of hMN with or without a rounded blunt tip micropillar, which suppresses skin deformation, around a hollow needle, and the effect on successful needle insertion and administration of a drug solution was investigated. Six different types of hMNs with needle lengths of 1000, 1300, and 1500 µm with or without a micropillar were used. METHODS: Needle insertion and the disposition of a drug in rat skin were investigated. In addition, the displacement-force profile during application of hMNs was also investigated using a texture analyzer with an artificial membrane to examine needle factors affecting successful insertion and administration of a drug solution by comparing with in vivo results. RESULTS: According to the results with the drug distribution of iodine, hMN1300 with a micropillar was able to successfully inject drug solution into an intradermal site with a high success rate. In addition, the results of displacement-force profiles with an artificial membrane showed that a micropillar can be effective for depth control of the injected solution as well as the prevention of contact between the hMN pedestal and the deformed membrane. CONCLUSION: In the present study, hMN1300S showed effective solution delivery into an intradermal site. In particular, a micropillar can be effective for depth control of the injected solution as well as preventing contact between the hMN pedestal and the deformed membrane. The obtained results will help in the design and development of hMNs that ensure successful injection of an administered drug.

Bioinspired and biomimetic strategies for inflammatory bowel disease therapy.

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory bowel disease with high morbidity and an increased risk of cancer or death, resulting in a heavy societal medical burden. While current treatment modalities have been successful in achieving long-term remission and reducing the risk of complications, IBD remains incurable. Nanomedicine has the potential to address the high toxic side effects and low efficacy in IBD treatment. However, synthesized nanomedicines typically exhibit some degree of immune rejection, off-target effects, and a poor ability to cross biological barriers, limiting the development of clinical applications. The emergence of bionic materials and bionic technologies has reshaped the landscape in novel pharmaceutical fields. Biomimetic drug-delivery systems can effectively improve biocompatibility and reduce immunogenicity. Some bioinspired strategies can mimic specific components, targets or immune mechanisms in pathological processes to produce targeting effects for precise disease control. This article highlights recent research on bioinspired and biomimetic strategies for the treatment of IBD and discusses the challenges and future directions in the field to advance the treatment of IBD.

Focused ultrasound-mediated blood-brain barrier opening is safe and feasible with moderately hypofractionated radiotherapy for brainstem diffuse midline glioma.

BACKGROUND: Diffuse midline glioma (DMG) is a pediatric tumor with dismal prognosis. Systemic strategies have been unsuccessful and radiotherapy (RT) remains the standard-of-care. A central impediment to treatment is the blood-brain barrier (BBB), which precludes drug delivery to the central nervous system (CNS). Focused ultrasound (FUS) with microbubbles can transiently and non-invasively disrupt the BBB to enhance drug delivery. This study aimed to determine the feasibility of brainstem FUS in combination with clinical doses of RT. We hypothesized that FUS-mediated BBB-opening (BBBO) is safe and feasible with 39 Gy RT. METHODS: To establish a safety timeline, we administered FUS to the brainstem of non-tumor bearing mice concurrent with or adjuvant to RT; our findings were validated in a syngeneic brainstem murine model of DMG receiving repeated sonication concurrent with RT. The brainstems of male B6 (Cg)-Tyrc-2J/J albino mice were intracranially injected with mouse DMG cells (PDGFB+, H3.3K27M, p53-/-). A clinical RT dose of 39 Gy in 13 fractions (39 Gy/13fx) was delivered using the Small Animal Radiation Research Platform (SARRP) or XRAD-320 irradiator. FUS was administered via a 0.5 MHz transducer, with BBBO and tumor volume monitored by magnetic resonance imaging (MRI). RESULTS: FUS-mediated BBBO did not affect cardiorespiratory rate, motor function, or tissue integrity in non-tumor bearing mice receiving RT. Tumor-bearing mice tolerated repeated brainstem BBBO concurrent with RT. 39 Gy/13fx offered local control, though disease progression occurred 3-4 weeks post-RT. CONCLUSION: Repeated FUS-mediated BBBO is safe and feasible concurrent with RT. In our syngeneic DMG murine model, progression occurs, serving as an ideal model for future combination testing with RT and FUS-mediated drug delivery.

ON/OFF based synergetic plasmonic photothermal drug release approach through core-satellite like mussel-inspired polydopamine nanoparticles.

One of the studies on new drug delivery and release systems that has increased in recent years is the study using plasmonic nanoparticles. In this study, polydopamine nanoparticles (PDOP NPs), which contribute to photothermal drug release by near infrared radiation (NIR), were decorated with gold nanoparticles (AuNPs) to utilize their plasmonic properties, and a core-satellite-like system was formed. With this approach, epirubicin (EPI)-loaded PDOP NPs were prepared by utilizing the plasmonic properties of AuNPs. Scanning Electron Microscope (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Diffraction (XRD) methods were used to evaluate the structural properties of these particles. The release behavior of the prepared structures in acidic (pH 5.0) and neutral (pH 7.4) environments based on the ON/OFF approach was also examined. The biocompatibility properties of the particles were evaluated on mouse fibroblast (L929) and anticancer activities on neuroblastoma (SH-SY5Y) cells. The effects of prepared EPI-loaded particles and laser-controlled drug release on ROS production, genotoxicity, and apoptosis were also investigated in SH-SY5Y cells. With the calculated combination index (CI) value, it was shown that the activity of EPI-loaded AuNP@PDOP NPs increased synergistically with the ON/OFF-based approach. The developed combination approach is considered to be remarkable and promising for further evaluation before clinical use.

Biomaterials in Drug Delivery: Advancements in Cancer and Diverse Therapies-Review.

Nano-sized biomaterials are innovative drug carriers with nanometric dimensions. Designed with biocompatibility in mind, they enable precise drug delivery while minimizing side effects. Controlled release of therapeutic substances enhances efficacy, opening new possibilities for treating neurological and oncological diseases. Integrated diagnostic-therapeutic nanosystems allow real-time monitoring of treatment effectiveness, which is crucial for therapy personalization. Utilizing biomaterials as nano-sized carriers in conjunction with drugs represents a promising direction that could revolutionize the field of pharmaceutical therapy. Such carriers represent groundbreaking drug delivery systems on a nanometric scale, designed with biocompatibility in mind, enabling precise drug delivery while minimizing side effects. Using biomaterials in synergy with drugs demonstrates significant potential for a revolutionary impact on pharmaceutical therapy. Conclusions drawn from the review indicate that nano-sized biomaterials constitute an innovative tool that can significantly improve therapy effectiveness and safety, especially in treating neurological and oncological diseases. These findings should guide researchers towards further studies to refine nano-sized biomaterials, assess their effectiveness under various pathological conditions, and explore diagnostic-therapeutic applications. Ultimately, these results underscore the promising nature of nano-sized biomaterials as advanced drug carriers, ushering in a new era in nanomedical therapy.

Recent Advances in Synergistic Effect of Nanoparticles and Its Biomedical Application.

The synergistic impact of nanomaterials is critical for novel intracellular and/or subcellular drug delivery systems of minimal toxicity. This synergism results in a fundamental bio/nano interface interaction, which is discussed in terms of nanoparticle translocation, outer wrapping, embedding, and interior cellular attachment. The morphology, size, surface area, ligand chemistry and charge of nanoparticles all play a role in translocation. In this review, we suggest a generalized mechanism to characterize the bio/nano interface, as we discuss the synergistic interaction between nanoparticles and cells, tissues, and other biological systems. Novel perceptions are reviewed regarding the ability of nanoparticles to improve hybrid nanocarriers with homogeneous structures to enhance multifunctional biomedical applications, such as bioimaging, tissue engineering, immunotherapy, and phototherapy.

Polymeric liposomes targeting dual transporters for highly efficient oral delivery of paclitaxel.

A novel delivery system comprising N-succinic anhydride (N-SAA) and D-fructose co-conjugated chitosan (NSCF)-modified polymeric liposomes (NSCF-PLip) were designed to enhance oral delivery of paclitaxel (PTX) by targeting monocarboxylate transporters (MCT) and glucose transporters (GLUT). The synthesized NSCF was characterised by FT-IR and 1H NMR spectra. The prepared 30.78 % (degree of substitution of N-SAA) NSCF-PTX-PLip were approximately 150 nm in size, with a regular spherical shape, the zeta potential of -25.4 ± 5.13 mv, drug loading of 2.35 % ± 0.05 %, and pH-sensitive and slow-release characteristics. Compared with PTX-Lip, 30.78 % NSCF-PTX-PLip significantly enhanced Caco-2 cellular uptake via co-mediation of MCT and GLUT, showing relatively specific binding of propionic acid and MCT. Notably, the NSCF modification of PTX-Lip had no appreciable influence on their original cellular uptake pathway. The fructose modification of 30.78 % NSC-PTX-PLip significantly increased the concentration after tmax, indicating their continuous and efficient absorption. Compared with PTX-Lip, the 30.78 % NSCF-PTX-PLip resulted in a 2.09-fold extension of MRT, and a 6.06-fold increase of oral bioavailability. It significantly increased tumour drug distribution and tumour growth inhibition rate. These findings confirm that 30.78 % NSCF-PLip offer a potential oral delivery platform for PTX and targeting the dual transporters of MCT and GLUT is an effective strategy for enhancing the intestinal absorption of drugs.