Potential Drug Delivery System Research Articles

Enhancing Drug Delivery of Glatiramer Acetate Through in Vitro Development of Controlled-Release Nanoliposomes: Investigating Drug Release Kinetics and Cytotoxic Effects

Background: Multiple sclerosis (MS) damages the myelin sheath covering nerve fibers. This condition affects 400,000 individuals in the United States and 2.5 million people globally, with a higher rate of diagnosis in women aged 20 - 40, with a ratio of 2:1. Liposomes facilitate drug dispersion, making them valuable in biomedicine. They enhance the stability of therapeutic medications, improve cellular and tissue absorption, and increase chemical bioactivity at specific locations. This technique delivers encapsulated compounds with high precision while minimizing negative consequences observed in laboratory settings. Objectives: This study aims to develop an optimal nanoliposome formulation using glatiramer acetate (GA) as the active pharmaceutical ingredient by examining drug release and associated adverse effects to achieve the most effective nanoliposomal system. Methods: The thin layer hydration method was used to prepare nanoliposomes. A comprehensive array of analytical techniques, including FE-SEM, FTIR, XRD, HPLC, and DLS, were employed to examine the physicochemical characteristics of the product. Additionally, the biosafety of the nanoliposomes was assessed using the MTT assay on the 1321N1 human astrocytoma cell line. The release profile of GA from the carrier was studied using the dialysis diffusion method, and the stability of the nanoliposomes was also inspected. Results: The size, Polydispersity Index (PDI), and zeta potential of the nanoliposomes were 91.2 ± 1.3 nm, 0.34 ± 0.03, and -27.3 ± 1.2 mV, respectively. The drug entrapment efficiency (DEE%) in nanoliposomes was approximately 70.2 ± 1.7%. The results from XRD and FTIR revealed no chemical interaction between the drug and carrier, and the nanoliposomes were safe for the cultured cell line. The nanoliposomes were stable under storage conditions and exhibited a sustained release profile. Conclusions: Nanoliposomes, as drug carriers, are known to be a potent drug delivery system due to their numerous advantages. Based on the results, GA-nanoliposomes show promise as a strategy for treating MS patients, pending further in vivo experiments and clinical trials.

Extracellular vesicles as drug delivery systems in therapeutics: current strategies and future challenges

Abstract Background Extracellular vesicles (EVs), which are nanometer-sized vesicles enclosed by lipid membranes, are secreted by most cells and contain lipids, proteins, and various nucleic acid species from the source cell. Due to their natural origin, high biocompatibility, stability, targeting ability, multifunctionality, and low immunogenicity, EVs have been increasingly explored as potential drug delivery system (DDS) agents, offering new strategies for the treatment of cardiovascular disease, neurodegenerative disease, cancer and many other diseases. However, there are several challenges facing EVs as drug delivery systems, such as the low drug loading efficiency and the need for consensus on ideal cell types as sources for EVs at the clinical level. Area Covered This article briefly reviews the physiological characteristics of EVs and discusses the applicable conditions for endogenous and exogenous drug loading in EVs, as well as the delivery modes of EVs as carriers. Finally, the challenges of EVs stability and drug encapsulation efficiency of EVs as future DDS are also described. Expert Opinion This article mainly focused on the different methods of endogenous and exogenous drug loading, described the delivery modes of EVs as carriers in drug delivery, and the challenges of stability and drug encapsulation efficiency facing in the future in detail and deeply.

Unlocking the Potential of Drug Delivery Systems: A Comprehensive Review of Formulation Strategies and Technologies in the Field of Pharmaceutics

: The creation of innovative drug delivery systems to enhance therapeutic effectiveness, safety, and patient compliance has resulted in considerable developments in pharmaceutics in recent years. The most recent formulation techniques and technologies are reviewed in this article to improve medication distribution and accomplish specific therapeutic goals. : This article thoroughly summarizes the most recent formulation techniques and technologies used to enhance medication delivery and provide specific therapeutic effects. It discusses the variety of medication delivery methods, including nanoparticles, liposomes, micelles, and dendrimers, and explores the application of nanotechnology and biotechnology in drug delivery. Additionally, the paper emphasizes the significance of targeted drug delivery systems and their capacity to cross biological barriers including the blood-brain barrier and tumor microenvironment. : The review also addresses the challenges faced in developing and commercializing drug delivery systems and suggests potential solutions to overcome them. Furthermore, the article emphasizes the role of computational modeling and simulation in designing and optimizing drug delivery systems. : Overall, this review paper offers insightful information for pharmaceutics researchers, scientists, and practitioners that will help in the creation of novel drug delivery systems that improve patient outcomes and quality of life.

P01-81 Exploring Gold/PLGA nanoparticles as potential drug-delivery system in a co-culture blood-brain barrier model

P01-81 Exploring Gold/PLGA nanoparticles as potential drug-delivery system in a co-culture blood-brain barrier model

Evaluation of 3-O-β-D-galactosylated resveratrol-loaded polydopamine nanoparticles for hepatocellular carcinoma treatment

In our previous studies, 3-O-β-D-galactosylated resveratrol (Gal-Res) was synthesized by structural modification and then 3-O-β-D-galactosylated resveratrol polydopamine nanoparticles (Gal-Res NPs) were successfully prepared to improve the bioavailability and liver distribution of Res. However, the pharmacodynamic efficacy and specific mechanism of Gal-Res NPs on hepatocellular carcinoma remain unclear. Herein, liver cancer model mice were successfully constructed by xenograft tumor modeling. Gal-Res NPs (34.2 mg/kg) significantly inhibited tumor growth of the liver cancer model mice with no significant effect on their body weight and no obvious toxic effect on major organs. Additionally, in vitro cellular uptake assay showed that Gal-Res NPs (37.5 μmol/L) increased the uptake of Gal-Res by Hepatocellular carcinoma (HepG2) cells, and significantly inhibited the cell migration and invasion. The experimental results of Hoechst 33342/propyl iodide (PI) double staining and flow cytometry both revealed that Gal-Res NPs could remarkably promote cell apoptosis. Moreover, the Western blot results revealed that Gal-Res NPs significantly regulated the Bcl-2/Bax and AKT/GSK3β/β-catenin signaling pathways. Taken together, the in vitro/in vivo results demonstrated that Gal-Res NPs significantly improved the antitumor efficiency of Gal-Res, which is a potential antitumor drug delivery system.

Engineering Platelet Membrane Imitating Nanoparticles for Targeted Therapeutic Delivery.

Platelet Membrane Imitating Nanoparticles (PMINs) is a novel drug delivery system that imitates the structure and functionality of platelet membranes. PMINs imitate surface markers of platelets to target specific cells and transport therapeutic cargo. PMINs are engineered by incorporating the drug into the platelet membrane and encapsulating it in a nanoparticle scaffold. This allows PMINs to circulate in the bloodstream and bind to target cells with high specificity, reducing off-target effects and improving therapeutic efficacy. The engineering of PMINs entails several stages, including the separation and purification of platelet membranes, the integration of therapeutic cargo into the membrane, and the encapsulation of the membrane in a nanoparticle scaffold. In addition to being involved in a few pathological conditions including cancer, atherosclerosis, and rheumatoid arthritis, platelets are crucial to the body's physiological processes. This study includes the preparation and characterization of platelet membrane-like nanoparticles and focuses on their most recent advancements in targeted therapy for conditions, including cancer, immunological disorders, atherosclerosis, phototherapy, etc. PMINs are a potential drug delivery system that combines the advantages of platelet membranes with nanoparticles. The capacity to create PMMNs with particular therapeutic cargo and surface markers provides new possibilities for targeted medication administration and might completely change the way that medicine is practiced. Despite the need for more studies to optimize the engineering process and evaluate the effectiveness and safety of PMINs in clinical trials, this technology has a lot of potential.

Cellulolytic characterization of the rumen-isolated Acinetobacter pittii ROBY and design of a potential controlled-release drug delivery system

A novel cellulolytic bacterial strain, ROBY, was isolated from a bovine rumen sample using the enrichment culture method. This isolate was found to be Acinetobacter pittii, with >99 % similarity according to 16S rRNA gene sequence analysis. The potential use of this strain in combination with doxorubicin (Dox)-integrated cellulose nanoparticles (Dox-CNPs) was evaluated as a proof-of-concept study for the further development of this approach as a novel controlled-release drug delivery strategy. The isolate can utilize CNPs as the sole carbon source for growth and degrade both Dox-CNPs and empty CNPs with high efficiency. Extracellular cellulases isolated from bacteria may also be used to trigger Dox release. The results also demonstrated that the release of Dox into the environment due to nanoparticle degradation in the samples incubated with Dox-CNPs significantly affected bacterial cell viability (∼75 % decrease), proving the release of Dox due to bacterial cellulase activity and suggesting the great potential of this approach for further development.

Development of Norelgestromin Dissolving Bilayer Microarray Patches for Sustained Release of Hormonal Contraceptive.

Microarray patches (MAPs) offer a noninvasive and patient-friendly drug delivery method, suitable for self-administration, which is especially promising for low- and middle-income country settings. This study focuses on the development of dissolving bilayer MAPs loaded with norelgestromin (NGMN) as a first step towards developing a future potential drug delivery system for sustained hormonal contraception. The fabricated MAPs were designed with the appropriate needle lengths to penetrate the stratum corneum, while remaining minimally stimulating to dermal nociceptors. Ex vivo assessments showed that the MAPs delivered an average of 176 ± 60.9 μg of NGMN per MAP into excised neonatal porcine skin, representing 15.3 ± 5.3% of the loaded drug. In vivo pharmacokinetic analysis in Sprague Dawley rats demonstrated a Tmax of 4 h and a Cmax of 67.4 ± 20.1 ng/mL for the MAP-treated group, compared to a Tmax of 1 h and a Cmax of 700 ± 138 ng/mL for the intramuscular (IM) injection group, with a relative bioavailability of approximately 10% for the MAPs. The MAP-treated rats maintained plasma levels sufficient for therapeutic effects for up to 7 days after a single application. These results indicate the potential of NGMN-loaded dissolving bilayer MAPs, with further development focused on extending the release duration and improving bioavailability for prolonged contraceptive effects.

Thermosensitive Hydrogels as Targeted and Controlled Drug Delivery Systems: Potential Applications in Transplantation.

Drug delivery in transplantation plays a vital role in promoting graft survival, preventing rejection, managing complications, and contributing to positive patient outcomes. Targeted and controlled drug delivery can minimize systemic effects. Thermosensitive hydrogels, due to their unique sol-gel transition properties triggered by thermo-stimuli, have attracted significant research interest as a potential drug delivery system in transplantation. This review describes the current status, characteristics, and recent applications of thermosensitive hydrogels for drug delivery. Studies aimed at improving allotransplantation outcomes using thermosensitive hydrogels are then elaborated on. Finally, the challenges and opportunities associated with their use are discussed. Understanding the progress of research will serve as a guide for future improvements in their application as a means of targeted and controlled drug delivery in translational therapeutic applications for transplantation.

Effect of Calcium Chloride on Chitosan Behavior in an Acidic Water Mixture for Pharmaceutical and Biomedical Applications

The present article reviews the uses of the biopolymer chitosan (CH) and its derivatives as versatile biomaterials for potential drug delivery systems, as well as for tissue engineering applications, analgesia and treatment of arthritis. CH and its derivatives, as natural antimicrobial agents, can be applied in biomedical, biotechnological, and pharmaceutical applications. Its antimicrobial activity depends on many factors, such as its molecular size, source, associated components, concentration and type of microorganism. In addition, in our research described here, we prepared and characterized the dynamic viscosity and the rheological properties of a biopolymer material based on CH/CaCl2 in solution. The dynamic viscosity and shear stress were measured under the influence of an increasing CH concentration of 1 to 10 g/l and an increasing temperature of 288.15 to 318.15 K.

Deciphering the drug delivery potential of Type1 lipid transfer protein from Citrus sinensis for enhancing the therapeutic efficacy of drugs

Type1 Non-specific Lipid Transfer Protein (CsLTP1) from Citrus sinensis is a small cationic protein possessing a long tunnel-like hydrophobic cavity. CsLTP1 performing membrane trafficking of lipids is a promising candidate for developing a potent drug delivery system. The present work includes in-silico studies and the evaluation of drugs binding to CsLTP1 using biophysical techniques along with the investigation of CsLTP1's ability to enhance the efficacy of drugs employing cell-based bioassays. The in-silico investigations identified Panobinostat, Vorinostat, Cetylpyridinium Chloride, and Fulvestrant with higher affinities and stability of binding to the hydrophobic pocket of CsLTP1. SPR studies revealed strong binding affinities of anticancer drugs, Panobinostat (KD = 1.40 μM) and Vorinostat (KD = 2.17 μM) to CsLTP1 along with the binding and release kinetics. CD and fluorescent spectroscopy revealed drug-induced conformational changes in CsLTP1. CsLTP1-associated drug forms showed remarkably enhanced efficacy in MCF-7 cells, representing increased cell cytotoxicity, intracellular ROS, reduced mitochondrial membrane potential, and up-regulation of proapoptotic markers than the free drugs employing qRT-PCR and western blot analysis. The findings demonstrate that CsLTP1 binds strongly to hydrophobic drugs to facilitate their transport, hence improving their therapeutic efficacy revealed by the in-vitro investigations. This study establishes an excellent foundation for developing CsLTP1-based efficient drug delivery system.

Polyelectrolyte complexes of chitosan and hyaluronic acid or carboxymethylpullulan and their aminoguaiacol derivatives with biological activities as potential drug delivery systems

Polyelectrolyte complexes (PECs) were elaborated from chitosan as cationic polymer and carboxy-methylpullulan (CMP), hyaluronic acid (HA) and their derivatives grafted with aminoguaiacol (G) with different degrees of substitution (DSGA) with the aim of obtaining nanogels for drug delivery. For each couple of polysaccharides, the charge ratios giving the smaller size with the lower PDI were selected to produce PECs. CMP_CHIT and CMP-G_CHIT PECs had smaller sizes (220–280 nm) than HA_CHIT and HA-G_CHIT PECs (280–390 nm). PECs were stable at 4 °C during 28 days at pH 5. In phosphate buffer saline (PBS) at pH 7.4, at 4 °C, a better stability of PECs based on CMP-G derivatives was observed. The hydrophobic associations between aminoguaiacol groups (highlighted by measurements of pyrene fluorescence) led to a better PECs' stabilization in PBS. The PECs' antioxidant and antibacterial activities were demonstrated and related to the DSGA. Diclofenac and curcumin were used as drug models: their loading reached 260 and 53 μg/mg PEC, respectively. The release of diclofenac in PBS at 37 °C followed a quasi-Fickian diffusion mechanism with release constant between 0.88 and 1.04 h−1. The curcumin release followed a slow linear increase in PBS/EtOH (60/40 V/V) with an effect of DSGA.

Enhanced anti-breast cancer activity of green synthesized selenium nanoparticles by PEGylation: induction of apoptosis and potential anticancer drug delivery system

Breast cancer is a disease associated with high morbidity and mortality rates worldwide. The potential use of biogenic nanoparticles as alternative anticancer agents has been immensely acknowledged in several studies, particularly selenium nanoparticles (SeNPs). Nanoparticles were synthesised using the aqueous extract of Moringa peregrine (MPM-SeNPs) and were PEGylated (PEG-MPM-SeNPs). MPM-SeNPs were characterised by chemical and physical techniques. The successful capping of MPM-SeNPs with PEG was confirmed by spectrophotometric measurements and via Fourier-transform infrared spectroscopy (FT-IR) analysis. Furthermore, the effect of PEGylation of MPM-SeNPs on enhancing their anti-breast cancer activity and as a drug delivery agent was evaluated. Therefore, the loading efficiency and release of DOX at different pH values were measured; the antiproliferative activity of PEG-MPM-SeNPs against the adenocarcinoma breast cancer cell line (MDA-MB-231) was evaluated and compared with that of biogenic MPM-SeNPs and DOX-conjugated PEG-MPM-SeNPs. PEG-MPM-SeNPs and DOX-PEG-MPM-SeNPs had reduced IC50 values compared to MPM-SeNPs; IC50 of 11.54 ± 1.74 and 31.27 ± 2.9 μg mL−1 compared to 71.4 ± 3.4 μg mL−1, respectively. MPM-SeNPs and PEG-MPM-SeNPs caused apoptosis to MDA-MB-231 cells with a significant decrease in the mitochondrial membrane potential (MMP), increase in the released cytochrome C (Cyt C), and activation of caspase-3/9 (P < 0.05). Linking DOX to PEG-MPM-SeNPs led to an increase in caspase-3/8 concentrations and an increase in the released Cyt C, but there were non-significant differences in MMP (P > 0.1) between treated and untreated control cancer cells. MPM-SeNPs and PEG-MPM-SeNPs caused apoptotic reactions via an intrinsic pathway, while linking DOX to PEG-MPM-SeNPs caused apoptosis in cancer cells through an extrinsic pathway.

ZINC PECTINATE-SESBANIA GUM-MEDIATED INTERPENETRATING POLYMER NETWORK-BASED MICROBEADS AS A CANDIDATE FOR FLOATING DRUG DELIVERY OF ESOMEPRAZOLE

This study aimed to develop esomeprazole-loaded zinc-pectinate-Sesbania gum floating microbeads, optionally supplemented with calcium silicate, as a gastro-retentive drug delivery system. The microbeads were produced using the ionic gelation method, with zinc acetate as the crosslinking agent, and were characterized through in vitro studies. The findings revealed that all formulations exhibited high drug encapsulation efficiency and sustained drug release profiles. Polymer ratios, calcium silicate incorporation, and the choice of low-density oils significantly influenced drug encapsulation efficiency and release kinetics. Notably, the B:6 batch, formulated with Sesbania gum and low methoxy pectin, demonstrated outstanding performance, releasing 95.89 ± 1.66% of the drug within 7 h, with a floating lag time of 1.18 ± 0.07 min, indicating promising in vitro gastro-retention capabilities. Analysis of P-XRD, FT-IR, SEM, and DSC data highlighted changes in crystallinity, drug–excipient compatibility, surface morphology, and thermal behavior of esomeprazole and esomeprazole-loaded microbeads. In conclusion, these floating microbeads represent a potential gastro-retentive drug delivery system, offering enhanced buoyancy and prolonged drug release, with potential therapeutic advantages for peptic ulcer management.

Impact of Cross‐Linking on the Physicochemical and Physiological Characteristics of Barnyard Millet (Echinochloa frumentacea) Grains Starch

Barnyard millet starch (Echinochloa frumentacea) has been investigated for its potential in drug delivery systems due to its unique properties. This study examined the physicochemical and physiological properties of cross‐linked barnyard millet starch (BMS) using varying concentrations of sodium tripolyphosphate (STPP). Physicochemical and physiological properties of the cross‐linked starches are analyzed. Cross‐linking resulted in reduced swelling capacity and solubility of starch samples. Morphological analysis revealed rough surfaces with cavities and minute cracks in cross‐linked starches. Acute and sub‐acute toxicity studies in test animals indicated no adverse effects, with LD50 values within acceptable limits at 2000 mg kg−1. Hematological, biochemical, and lipid profiles showed no significant alterations compared to the control group. The study demonstrated a low acute toxicity level and favorable safety profile for STPP‐cross‐linked starch. These findings highlighted the potential of cross‐linked barnyard millet starch as a carrier in drug delivery system and for food applications. This study supports the potential of cross‐linked barnyard millet starch in pharmaceutical formulations.

Risperidone/cyclodextrin inclusion complex electrospun nanofibers for fast-disintegrating antipsychotic drug delivery

In this paper, the inclusion complexes (ICs) of hydroxypropyl-beta-cyclodextrin (HPβCD) and risperidone were electrospun into nanofibrous film for potential fast-disintegrating drug delivery system. Risperidone is used to treat bipolar disorder, schizophrenia, and mood swings from autism. However, it is practically insoluble in aqueous medium. On the other hand, the encapsulation of risperidone into HPβCD cavity by inclusion complexation can enhance water solubility of this drug molecule. Here, the IC systems were prepared with 4/1 and 2/1 M ratio (HPβCD/risperidone). The highly concentrated HPβCD aqueous solutions (200 %, w/v) were used for the fiber formation. Finally, the system having 4/1 M ratio resulted in a clear and homogeneous solution showing that the HPβCD and risperidone completely formed IC. However, HPβCD/risperidone-IC having 2/1 M ratio was turbid and contained some small clumps of un-complexed risperidone. Even so, free-standing and thin nanofibrous films were obtained for both systems with an average fiber diameter of ∼315 nm and ∼280 nm for 2/1 and 4/1 systems, respectively. Both HPβCD/risperidone-IC nanofibers were produced with approximately 100 % preservation of risperidone within the nanofiber matrix without the loss of risperidone during electrospinning process, that is, HPβCD/risperidone-IC nanofibers retained the initial M ratio of 2/1 and 4/1 as in electrospinning solution. Both HPβCD/risperidone-IC nanofibrous films showed fast-disintegration and fast-release characteristics in artificial saliva and aqueous medium verifying their potential as a fast-disintegrating oral drug delivery system for risperidone.

Alginate Nanoparticles Containing Cuminum cyminum and Zataria multiflora Essential Oils with Promising Anticancer and Antibacterial Effects.

Cancer and bacterial infections are major global health concerns driving the need for innovative medicines. This study investigated alginate nanoparticles loaded with essential oils (EOs) from Cuminum cyminum and Zataria multiflora as potential drug delivery systems. The nanoparticles were comprehensively characterized using techniques such as gas chromatography-mass spectrometry (GC-MS), dynamic light scattering (DLS), zetasizer, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and ultraviolet-visible spectroscopy (UV-Vis). Their biological properties against two human skin cancer cell lines (A-375 and A-431) and three bacteria (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) were also evaluated. Alginate nanoparticles containing C. cyminum and Z. multiflora EOs exhibited sizes of 160 ± 8 nm and 151 ± 10 nm, respectively. Their zeta potentials and encapsulation efficiencies were -18 ± 1 mV and 79 ± 4%, as well as -27 ± 2 mV and 86 ± 5%, respectively. The IC50 values against the tested cell lines and bacteria revealed superior efficacy for nanoparticles containing Z. multiflora EO. Considering the proper efficacy of the proposed nanoparticles, the straightforward preparation method and low cost suggest their potential for further in vivo studies.

Nonintuitive Immunogenicity and Plasticity of Alpha-Synuclein Conformers: A Paradigm for Smart Delivery of Neuro-Immunotherapeutics.

Despite the extensive research successes and continuous developments in modern medicine in terms of diagnosis, prevention, and treatment, the lack of clinically useful disease-modifying drugs or immunotherapeutic agents that can successfully treat or prevent neurodegenerative diseases is an ongoing challenge. To date, only one of the 244 drugs in clinical trials for the treatment of neurodegenerative diseases has been approved in the past decade, indicating a failure rate of 99.6%. In corollary, the approved monoclonal antibody did not demonstrate significant cognitive benefits. Thus, the prevalence of neurodegenerative diseases is increasing rapidly. Therefore, there is an urgent need for creative approaches to identifying and testing biomarkers for better diagnosis, prevention, and disease-modifying strategies for the treatment of neurodegenerative diseases. Overexpression of the endogenous α-synuclein has been identified as the driving force for the formation of the pathogenic α-synuclein (α-Syn) conformers, resulting in neuroinflammation, hypersensitivity, endogenous homeostatic responses, oxidative dysfunction, and degeneration of dopaminergic neurons in Parkinson's disease (PD). However, the conformational plasticity of α-Syn proffers that a certain level of α-Syn is essential for the survival of neurons. Thus, it exerts both neuroprotective and neurotoxic (regulatory) functions on neighboring neuronal cells. Furthermore, the aberrant metastable α-Syn conformers may be subtle and difficult to detect but may trigger cellular and molecular events including immune responses. It is well documented in literature that the misfolded α-Syn and its conformers that are released into the extracellular space from damaged or dead neurons trigger the innate and adaptive immune responses in PD. Thus, in this review, we discuss the nonintuitive plasticity and immunogenicity of the α-Syn conformers in the brain immune cells and their physiological and pathological consequences on the neuroimmune responses including neuroinflammation, homeostatic remodeling, and cell-specific interactions that promote neuroprotection in PD. We also critically reviewed the novel strategies for immunotherapeutic delivery interventions in PD pathogenesis including immunotherapeutic targets and potential nanoparticle-based smart drug delivery systems. It is envisioned that a greater understanding of the nonintuitive immunogenicity of aberrant α-Syn conformers in the brain's microenvironment would provide a platform for identifying valid therapeutic targets and developing smart brain delivery systems for clinically effective disease-modifying immunotherapeutics that can aid in the prevention and treatment of PD in the future.

Hybrid adipocyte-derived exosome nano platform for potent chemo-phototherapy in targeted hepatocellular carcinoma

The high prevalence and severity of hepatocellular carcinoma (HCC) present a significant menace to human health. Despite the significant advancements in nanotechnology-driven antineoplastic agents, there remains a conspicuous gap in the development of targeted chemotherapeutic agents specifically designed for HCC. Consequently, there is an urgent need to explore potent drug delivery systems for effective HCC treatment. Here we have exploited the interplay between HCC and adipocyte to engineer a hybrid adipocyte-derived exosome platform, serving as a versatile vehicle to specifically target HCC and exsert potent antitumor effect. A lipid-like prodrug of docetaxel (DSTG) with a reactive oxygen species (ROS)-cleavable linker, and a lipid-conjugated photosensitizer (PPLA), spontaneously co-assemble into nanoparticles, functioning as the lipid cores of the hybrid exosomes (HEMPs and NEMPs). These nanoparticles are further encapsuled within adipocyte-derived exosome membranes, enhancing their affinity towards HCC cancer cells. As such, cancer cell uptakes of hybrid exosomes are increased up to 5.73-fold compared to lipid core nanoparticles. Our in vitro and in vivo experiments have demonstrated that HEMPs not only enhance the bioactivity of the prodrug and extend its circulation in the bloodstream but also effectively inhibit tumor growth by selectively targeting hepatocellular carcinoma tumor cells. Self-facilitated synergistic drug release subsequently promoting antitumor efficacy, inducing significant inhibition of tumor growth with minimal side effects. Our findings herald a promising direction for the development of targeted HCC therapeutics.

The application of phenylboronic acid pinacol ester functionalized ROS-responsive multifunctional nanoparticles in the treatment of Periodontitis

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.