Delivery Of Substances Research Articles

A Journey Along the Boulevard of Bioactive Compounds from Natural Sources, with Cosmetic and Pharmaceutical Potential: Bee Venom, Cobra Venom, Ficus carica

Animal venom and plant extracts have been used since ancient times in traditional medicine worldwide. Natural components, valued for their safety and effectiveness, have been consistently used in cosmetic and pharmaceutical applications. We propose a journey along the boulevard of active compounds from natural sources, where bee venom (BV), cobra venom (CV), and Ficus carica reveal their individual therapeutic and cosmetic properties. The originality of this review lies in exploring the synergy of these bioactive sources, an approach that has not been presented in the literature. Although BV, CV, and Ficus carica have different origins and compositions, they have multiple common pharmacological and cosmetic actions, which make them ideal for inclusion in various products that can be used for skin care and health in general. Their anti-inflammatory, antioxidant, immunomodulatory, antimicrobial, neuroprotective, and regenerative properties give them an essential role in the creation of potential innovative and effective products in the pharmaceutical and cosmetics industry. Although many plant extracts have antioxidant and anti-inflammatory properties, Ficus carica was chosen due to its complex biochemical composition, which provides valuable benefits in skin regeneration and protection against oxidative stress. According to the International Nomenclature of Cosmetic Ingredients (INCI), Ficus carica is used in the form of an extract of fruits, leaves, juice, bark or stem, each having specific applicability in topical formulations; due to the diversity of bioactive compounds, it can amplify the effectiveness of BV and CV, helping to enhance their beneficial effects and reducing the risk of adverse effects, due to its well-tolerated nature. Thus, this combination of natural ingredients opens up new perspectives in the development of innovative products, optimizing efficiency and maintaining a favorable safety profile. In this context, due to the reported experimental results, the three natural sources caught our attention, and we conceived the present work, which is a review made following the analysis of the current progress in the study of the bioactive compounds present in BV, CV, and Ficus carica. We focused on the novelties regarding pharmacological and cosmetic actions presented in the literature, and we highlighted the safety profile, as well as the modern approaches regarding the delivery and transport systems of the active substances from the three natural sources, and we evaluated their prospects in therapeutic and cosmetic use. This paper not only expands our knowledge of bioactive compounds, but it can also generate new ideas and motivations for the research and development of innovative treatments and skincare methods.

Food Gels Based on Polysaccharide and Protein: Preparation, Formation Mechanisms, and Delivery of Bioactive Substances

Hydrogels have a unique three-dimensional network that can create a good environment for the loading of functional compounds; hence, they have considerable potential in the delivery of bioactive substances. Natural macromolecular substances (proteins, polysaccharides) have the features of low toxicity, degradability, and biosafety; thus, they can be employed in the manufacture of hydrogels in the food sector. With its customizable viscoelastic and porous structure, hydrogels are believed to be good bioactive material delivery vehicles, which can effectively load polyphenols, vitamins, probiotics, and other active substances to prevent their influence from the external environment, thereby improving its stability. In this research, the common raw materials, preparation methods, and applications in the delivery of bioactive elements of food gels were examined; this study aimed at presenting new ideas for the development and utilization of protein-based food gels.

Advancements in Nanohydroxyapatite: Synthesis, Biomedical Applications, and Composite Developments

Abstract Nanohydroxyapatite (nHA) is distinguished by its exceptional biocompatibility, bioactivity, and biodegradability, qualities attributed to its similarity to the mineral component of human bone. This review discusses the synthesis techniques of nHA, highlighting how these methods shape its physicochemical attributes and, in turn, its utility in biomedical applications. The versatility of nHA is further enhanced by doping with biologically significant ions like magnesium or zinc, which can improve its bioactivity and confer therapeutic properties. Notably, nHA-based composites, incorporating metal, polymeric, and bioceramic scaffolds, exhibit enhanced osteoconductivity and osteoinductivity. In orthopedic field, nHA and its composites serve effectively as bone graft substitutes, showing exceptional osteointegration and vascularization capabilities. In dentistry, these materials contribute to enamel remineralization, mitigate tooth sensitivity, and are employed in surface modification of dental implants. For cancer therapy, nHA composites offer a promising strategy to inhibit tumor growth while sparing healthy tissues. Furthermore, nHA-based composites are emerging as sophisticated platforms with high surface ratio for the delivery of drugs and bioactive substances, gradually releasing therapeutic agents for progressive treatment benefits. Overall, this review delineates the synthesis, modifications, and applications of nHA in various biomedical fields, shed light on the future advancements in biomaterials research.

Maltodextrin vitamin E succinate: A novel antioxidant emulsifier for formulating functional nanoemulsions

A new multifunctional emulsifier was synthesized by coupling maltodextrin with a dextrose equivalent of 19 to vitamin E succinate. Two emulsifiers with varying degrees of vitamin E succinate substitution were prepared based on different mass ratios of vitamin E succinate to maltodextrin. The molecular structure and purity of these emulsifiers were analyzed. Nanoemulsions were prepared using octenyl succinic anhydride modified starch as a control to investigate the physical stability, antioxidant capacity, oxidative stability, and in vitro simulated digestive properties of the nanoemulsions. The emulsifying and antioxidant activity of the maltodextrin-vitamin E succinate conjugate was significantly superior to that of octenyl succinic anhydride modified starch, demonstrating good physical and oxidative stability. Additionally, they were rapidly digested under simulated small intestinal conditions. This new emulsifier shows broad application potential for the encapsulation, protection, and delivery of hydrophobic bioactive substances in the fields of medicine, food, and healthcare products.

Mesenchymal Stem Cells Target Gastric Cancer and Deliver Epirubicin via Tunneling Nanotubes for Enhanced Chemotherapy.

A reduced effective local concentration significantly contributes to the unsatisfactory therapeutic results of epirubicin in gastric cancer. Mesenchymal stem cells exhibit targeted chemotaxis towards solid tumors and form tunneling nanotubes with tumor cells, facilitating the delivery of various substances. This study demonstrates the novelty of mesenchymal stem cells in releasing epirubicin into gastric cancer cells through tunneling nanotubes. Epirubicin delivery to gastric cancer cells using mesenchymal stem cells. In vitro transwell migration assays, live cell tracking, and in vivo targeting assays were used to demonstrate the chemotaxis of mesenchymal stem cells towards gastric cancer. We verified the targeted chemotaxis of mesenchymal stem cells towards gastric cancer cells and the epirubicin loading ability using a high-content imaging system (Equipment type:Operetta CLS). Additionally, tunneling nanotube formation and the targeted release of epirubicin-loaded mesenchymal stem cells co-cultured with gastric cancer cells through mesenchymal stem cell-tunneling nanotubes into gastric cancer cells was observed using Operetta CLS. Mesenchymal stem cells demonstrated targeted chemotaxis towards gastric cancer, with effective epirubicin loading and tolerance. Co-culturing induced tunneling nanotube formation between these cells. Epirubicin-loaded mesenchymal stem cells were released into gastric cancer cells through tunneling nanotubes, significantly increasing their non-viability compared to the negative control group (p < 0.05). We identified a novel approach for precisely targeting epirubicin release in gastric cancer cells. Therefore, mesenchymal stem cell-tunneling nanotubes could serve as a potential tool for targeted delivery of drugs, enhancing their chemotherapeutic effects in cancer cells.

Chitosan Nanoparticles as a Potential Drug Delivery System in the Skin: A Systematic Review Based on In Vivo Studies

AbstractChitosan nanoparticles (ChNP) represent an interesting technological platform for drug delivery to the skin due to their mucoadhesive, nontoxic, and biodegradable characteristics, offering advantages in bypassing the stratum corneum and improving drug delivery in dermal administration. This systematic review analyzed the in vivo applicability of ChNP as a substance delivery system to the skin. A literature search was conducted in the databases PubMed, SciELO, and Lilacs using the keywords “nanoparticle,” “chitosan,” and “skin.” Inclusion criteria involved in vivo studies investigating the effects of topical use of these nanoparticles, published between 2013 and 2023, and comparing the nanoparticulate formulation with the free drug. The prevalence of studies conducted on animal models was 94.1%, while only 5.9% were performed on humans. The results suggest that ChNP formulations improved the delivery of therapeutic agents and demonstrated superior efficacy compared to formulations containing the free drug; they exhibited good permeability and tolerability, gradual release of the active molecule, and faster results with minimal adverse effects. Therefore, ChNP containing active substances for topical application emerges as a safe and effective platform with significant potential for drug delivery to the skin, opening new perspectives for their use in innovative formulations.

Proposal of classification and terminology of interventional endoscopic ultrasonography/endosonography.

Interventional endoscopic ultrasonography/endosongraphy (I-EUS) procedures have rapidly evolved since their introduction three decades ago; however, the classification and terminology for these procedures remain unstandardized. To address this, the Subcommittee for Terminology of I-EUS in the Japan Gastroenterological Endoscopy Society was established to define classifications and a glossary of I-EUS terms. They categorized I-EUS procedures into five types based on purpose and method: (i) EUS-guided sampling; (ii) EUS-guided through-the-needle examination; (iii) EUS-guided drainage/anastomosis (EUS-D/A); (iv) trans-endosonographically/EUS-guided created route (ESCR) procedures; and (v) EUS-guided delivery. EUS-guided sampling includes tissue acquisition and fluid sampling, classified by needle type into fine needle aspiration and fine needle biopsy. Through-the-needle examinations include imaging, measurements, and biopsies. EUS-D/A includes organ drainage/anastomosis, fluid collection drainage, and digestive tract anastomosis. In the EUS-D/A route, "anastomosis" is used for organ-to-organ procedures, whereas "tract" is for fluid drainage. ESCR is a newly proposed term for procedures via anastomosis or tract, such as endoscopic necrosectomy and EUS-guided antegrade stenting. The term "trans-luminal drainage/anastomosis stent" is used for stents that maintain the ESCR rather than treating strictures. EUS-guided delivery involves the delivery of substances, such as fluids, drugs, medical devices, and energy. This proposed categorization and terminology aimed to clarify I-EUS procedures and will require updates as new techniques and concepts emerge.

Implementing Optogenetic-Controlled Bacterial Systems in Drosophila melanogaster for Alleviation of Heavy Metal Poisoning.

Drosophila melanogaster (fruit fly) is an animal model chassis in biological and genetic research owing to its short life cycle, ease of cultivation, and acceptability to genetic modification. While the D. melanogaster chassis offers valuable insights into drug efficacy, toxicity, and mechanisms, several obvious challenges such as dosage control and drug resistance still limit its utility in pharmacological studies. Our research combines optogenetic control with engineered gut bacteria to facilitate the precise delivery of therapeutic substances in D. melanogaster for biomedical research. We have shown that the engineered bacteria can be orally administered to D. melanogaster to get a stable density of approximately 28,000 CFUs/per fly, leading to no detectable negative effects on the growth of D. melanogaster. In a model of D. melanogaster exposure to heavy metal, these orally administered bacteria uniformly express target genes under green light control to produce MtnB protein for binding and detoxifying lead, which significantly reduces the level of oxidative stress in the intestinal tract of Pb-treated flies. This pioneering study lays the groundwork for using optogenetic-controlled bacteria in the model chassis D. melanogaster to advance biomedical applications.

Development of a zoledronate-modified functional alginate hydrogel with effects of promoting osteogenesis for potential osteoporosis treatment

Osteoporosis is one of the most prevalent age-related diseases worldwide. It is characterized by a systemic deterioration in bone strength (bone density and bone mass), leading to an increase in fragility fractures. The complex pathological environment of osteoporosis presents a significant challenge to the induction of bone regeneration under osteoporotic conditions. Therefore, the development of a system for local delivery of active substances with osteoinductive effects is of practical significance in the clinical treatment of osteoporosis. In this study, we successfully loaded the anti-osteoporotic small molecule drug zoledronate (ZOL) into calcium alginate to prepare a biologically functional hydrogel, designated as ALG-ZOL-Ca. The prepared ALG-ZOL-Ca hydrogel gels quickly, making the hydrogel easy to inject and adapt to irregularly shaped bone defects, and simultaneously exhibits good bioactivity and osteoconductivity. The RT-qPCR results suggested that this hydrogel effectively promoted the expression levels of β-catenin and Axin2, which indicating a stimulative effect on the Wnt/β-catenin pathway in vitro. Moreover, ALG-ZOL-Ca hydrogel effectively promoted the expression of the OCN and SP7 genes. Therefore, this study proposes a new functional composite hydrogel that provides a potential treatment strategy for osteoporosis.

UTILIZATION OF NANOTECHNOLOGY IN VETERINARY MEDICINE

In veterinary medicine, particularly in diagnostics, drug administration, and reproductive biology, nanotechnology has made significant contributions. By enabling the precise delivery of unstable or insoluble substances, reducing systemic toxicity, and prolonging the action of the active ingredient at the desired site, nanoparticles enhance the effectiveness of treatments. This translates to fewer doses, reduced costs, and less waste from animal-derived products. Furthermore, nanotechnology aids in diagnostics by detecting pathogens and mapping molecular profiles related to diseases. The sensitivity of tests, increased by nanoparticles, allows for more effective detection of contaminants and microbial agents in animal-derived products, which is crucial for food safety. Nanoparticles and nanotubes are also used in reproductive biology to improve fertility, extend sperm longevity, and facilitate semen purification for artificial insemination. Additionally, implanted nanotubes can monitor hormone levels, aiding in the identification of estrus and the selection of breeders. Despite these advancements, it is crucial to monitor the risks and environmental impacts of nanotechnological technologies to ensure their safety and effectiveness in veterinary medicine. The objective of this work is to explore and evaluate current applications of nanotechnology in veterinary medicine, highlighting its benefits, challenges, and potential for future advancements.

Egg yolk lecithin delivery system constructed by ovalbumin-fucoidan (OVA-FUC) binary complex: Storage stability, release yield and in vitro digestion characteristics

Unfavorable environmental factors limit the utilization of egg yolk lecithin in functional foods. Therefore, it is necessary to enhance its stability and effectiveness to cater to the diverse food needs of individuals. This study aimed to explore the feasibility of protecting and delivering egg yolk lecithin through O/W emulsions, which were stabilized using ovalbumin-fucoidan (OVA-FUC) binary complexes as emulsifiers. This study investigated the protective effect of OVA-FUC emulsion on egg yolk lecithin and its impact on delivery by examining the storage stability, in vitro release yield, and stability during in vitro digestion of egg yolk lecithin in the emulsion. The results indicate that egg yolk lecithin, when encapsulated in the OVA-FUC emulsion, exhibits a relatively stable behavior during simulated in vitro digestion. Additionally, encapsulation enhanced both the delivery efficiency and drug release of egg yolk lecithin. Furthermore, the thermal and light stability of egg yolk lecithin embedded in OVA-FUC emulsion was improved, significantly improving its storage performance. The emulsion, prepared using the OVA-FUC binary complex, effectively safeguarded and enhanced the delivery efficiency of bioactive substances as an encapsulating material, thus exhibiting immense potential for application in the active protection and delivery of such substances.

The Effect of Metallic Nanoparticles Supplementation in Semen Extender on Post-thaw Quality and Fertilizing Ability of Egyptian Buffalo (Bubalus bubalis) Spermatozoa.

Nanomaterials offer several promising prospects in the field of farm animal reproduction, encompassing a broad range of applications such as transgenesis and the precise delivery of substances to sperm cells, antimicrobial, antioxidants properties as well as their potent role in improving cryopreservation methods. The aim of the present study is to explore the effect of supplementing the semen extender with 10µg/mL nano gold (Au-NPs10), 10µg/mL nano silver (Ag-NPs10), 1µg/mL nano selenium (Se-NPs1), and 100µg/mL nano zinc oxide (ZnO-NPs100) on sperm characteristics and kinematics parameters, acrosome integrity, oxidative biomarkers, morphological and apoptosis-like changes of frozen-thawed buffalo bull sperm, and, ultimately, their fertilizing capacity. The results revealed that all aforementioned nano materials significantly improved viability, progressive motility, membrane integrity, acrosome integrity, and kinematic parameters as well as apoptosis-like changes of post-thawed buffalo bull sperm compared to the control (p < 0.05). No discernible effects were observed on sperm ultrastructure morphology measures as a response to the addition of these metallic nanoparticles to the extender. The values of caspase 3 significantly decreased by 64.22, 45.99, 75.59, and 49.39% in Au-NPs10, Ag-NPs10, Se-NPs1, and ZnO-NPs100treated groups, respectively, compared to the control. The addition of 100µg ZnO-NPs to the extender significantly decreased the total count of bacteria, fungi, and yeast compared to the control (p < 0.05). The AuNPs10 and SeNPs1 treated groups showed lower content of malondialdehyde, hydrogen peroxide, and nitric oxide concentrations and higher values of total antioxidant capacity of post-thawed extended semen (p < 0.05). Pregnancy rates increased by 17.5, 20, and 30% in buffalo cows inseminated with sperm treated with ZnO-NPs100, Se-NPs1, and Au-NPs10, respectively, compared to the control group. The present results indicate that the freezing extender supplemented with metallic nanoparticles can be an effective strategy to enhance the cryotolerance and fertility potential of buffalo bull sperm.

Physicochemical characterization of emulsions stabilized with polysaccharide conjugates extracted from Pu'er tea and their protective effect on curcumin

This study aimed to investigate the influence of different storage periods on the emulsifying properties of polysaccharide-protein complexes (pTPC) in Pu 'er tea through structural analysis and macroscopic characterization, and further explore the stability of pTPC-stabilized nano-emulsions in various environmental conditions. Through determination of chemical composition, interfacial tension, and infrared spectroscopy, it was found that compared to pTPC-13, the higher amino acid content of pTPC-18 led to enhanced hydrogen bonding and electrostatic interactions between intramolecular polysaccharides and polyphenols, thereby increasing its adsorption rate and interfacial film thickness. Additionally, the stability of pTPC-18 stabilized nano-emulsions showed no significant changes in zeta potential and particle size over 0–90 days of storage, pH 2.0–9.0, 25–100 °C, Na+ and Ca2+, whereas pTPC-13 stabilized emulsions exhibited noticeable droplet aggregation and layering instability under the same stress conditions. Furthermore, for curcumin encapsulation, pTPC-18 nano-emulsions (60%) demonstrated stronger protection of curcumin compared to pTPC-13 nano-emulsions (39%). These results suggest that during long-term storage, the relative increase in protein and polyphenol content within pTPC-18 enhances its emulsifying properties, providing new insights into the development of lipid-active substance delivery systems.

Optimization and Characterization of PEG Extraction Process for Tartary Buckwheat-Derived Nanoparticles.

Plant-derived edible nanovesicles serve as crucial nanocarriers for targeted delivery of bioactive substances, including miRNAs and phytochemicals, to specific tissues. They have emerged as a significant focus in precision nutrient delivery research. In this study, Tartary-buckwheat-derived nanoparticles (TBDNs) were isolated and purified using a combination of differential centrifugation and PEG precipitation. A response surface test was employed to optimize the extraction process of TBDNs in terms of yield, total phenol and flavonoid content, as well as antioxidant activity. The results demonstrated that TBDNs exhibited the highest yield and activity at a 10% concentration of PEG, pH 5, and centrifugation temperature of 4 °C. Under these conditions, the measured yield of TBDNs was 1.7795 g/kg, with a total phenol content of 178.648 mg/100 g, total flavonoid content of 145.421 mg/100 g, and DPPH-radical-scavenging rate reaching 86.37%. Characterization through a transmission electron microscope and nanoparticle-size-tracking analyzer revealed that TBDNs possessed a teato-type vesicle structure with dispersed vesicle clusters present within them. Furthermore, the extracted TBDNs were found to have an average particle size of 182.8 nm with the main peak observed at 162.8 nm when tested for particle size distribution analysis. These findings provide a novel method for extracting TBDNs while laying the groundwork for future investigations into their activities.

Substance Delivery across the Blood-Brain Barrier or the Blood-Retinal Barrier Using Organic Cation Transporter Novel Type 2 (OCTN2)

The membrane impermeability of a drug poses a significant challenge in drug research and development, preventing effective drug delivery to the target site. Specifically, the blood-brain barrier (BBB) presents a formidable obstacle to the delivery of drugs targeting the central nervous system (CNS) into the brain, whereas the blood-retinal barrier (BRB) presents a tremendous obstacle to the delivery of drugs targeting the ocular diseases into the eyes. The development of drugs for Alzheimer’s or Parkinson’s disease targeting the CNS and for diabetic retinopathy and age-related macular degeneration targeting the eyes remains an unmet medical need for patients. Transporters play a crucial physiological role in maintaining homeostasis in metabolic organs. Various types of solute carrier (SLC) transporters are expressed in the capillary endothelial cells of the BBB, facilitating the delivery of nutrients from the blood flow to the brain. Therefore, carrier-mediated transport across the BBB can be achieved using SLC transporters present in capillary endothelial cells. It is well-known that CNS drugs typically incorporate N-containing groups, indicating that cation transporters facilitate their transport into the brain. In fact, carrier-mediated transport across the BBB can be accomplished using glucose transporter type 1 (Glut1) as a glucose transporter, L-type amino acid transporter 1 (LAT1) as a large neutral amino acid transporter, and H+/cation antiporter as a cation transporter. Surprisingly, although organic cation transporter novel type 2 (OCTN2) is expressed in the capillary endothelial cells, there has been limited investigation into OCTN2-mediated substance delivery into the brain across the BBB. Furthermore, it is suggested that OCTN2 is expressed at the BRB. In this prospective review, I present the advantages and possibilities of substance delivery into the brain across the BBB or into the eyes across the BRB, mediated by OCTN2 via carrier-mediated transport or receptor-mediated transcytosis.

Modification of soybean lipophilic protein based on pH-shifting and high-pressure homogenization: Focus on structure, physicochemical properties and delivery vehicle

High-pressure homogenization and pH-shifting can be used to modify soybean lipophilic protein (SLP), and to enhance its ability to deliver vitamin B12. The structural changes of SLP were analyzed by multispectral techniques and the results showed that secondary and tertiary structures of SLP were altered by modification. The modification unfolded the SLP structure, released more free hydrogen ions, and increased positive charge density on the protein surface. Also, the solubility of modified SLP increased by maximum of 34.75 %. Furthermore, molecular docking showed that complexes were formed between SLP and vitamin B12 mainly through hydrogen bonding and hydrophobic interactions, and the encapsulation rate of modified SLP was maximally increased by 2.3 %. In vitro digestion showed that modified SLP enhanced stability and bioaccessibility of vitamin B12. This study provides theoretical basis for modification of SLP and effective delivery of bioactive substances.

Biohacking Nerve Repair: Novel Biomaterials, Local Drug Delivery, Electrical Stimulation, and Allografts to Aid Surgical Repair.

The regenerative capacity of the peripheral nervous system is limited, and peripheral nerve injuries often result in incomplete healing and poor outcomes even after repair. Transection injuries that induce a nerve gap necessitate microsurgical intervention; however, even the current gold standard of repair, autologous nerve graft, frequently results in poor functional recovery. Several interventions have been developed to augment the surgical repair of peripheral nerves, and the application of functional biomaterials, local delivery of bioactive substances, electrical stimulation, and allografts are among the most promising approaches to enhance innate healing across a nerve gap. Biocompatible polymers with optimized degradation rates, topographic features, and other functions provided by their composition have been incorporated into novel nerve conduits (NCs). Many of these allow for the delivery of drugs, neurotrophic factors, and whole cells locally to nerve repair sites, mitigating adverse effects that limit their systemic use. The electrical stimulation of repaired nerves in the perioperative period has shown benefits to healing and recovery in human trials, and novel biomaterials to enhance these effects show promise in preclinical models. The use of acellular nerve allografts (ANAs) circumvents the morbidity of donor nerve harvest necessitated by the use of autografts, and improvements in tissue-processing techniques may allow for more readily available and cost-effective options. Each of these interventions aid in neural regeneration after repair when applied independently, and their differing forms, benefits, and methods of application present ample opportunity for synergistic effects when applied in combination.

Research advances on signaling pathways regulating the polarization of tumor-associated macrophages in lung cancer microenvironment.

Lung cancer (LC) is one of the most common cancer worldwide. Tumor-associated macrophages (TAMs) are important component of the tumor microenvironment (TME) and are closely related to the stages of tumor occurrence, development, and metastasis. Macrophages are plastic and can differentiate into different phenotypes and functions under the influence of different signaling pathways in TME. The classically activated (M1-like) and alternatively activated (M2-like) represent the two polarization states of macrophages. M1 macrophages exhibit anti-tumor functions, while M2 macrophages are considered to support tumor cell survival and metastasis. Macrophage polarization involves complex signaling pathways, and blocking or regulating these signaling pathways to enhance macrophages' anti-tumor effects has become a research hotspot in recent years. At the same time, there have been new discoveries regarding the modulation of TAMs towards an anti-tumor phenotype by synthetic and natural drug components. Nanotechnology can better achieve combination therapy and targeted delivery of drugs, maximizing the efficacy of the drugs while minimizing side effects. Up to now, nanomedicines targeting the delivery of various active substances for reprogramming TAMs have made significant progress. In this review, we primarily provided a comprehensive overview of the signaling crosstalk between TAMs and various cells in the LC microenvironment. Additionally, the latest advancements in novel drugs and nano-based drug delivery systems (NDDSs) that target macrophages were also reviewed. Finally, we discussed the prospects of macrophages as therapeutic targets and the barriers to clinical translation.

Refinement of intranasal delivery in rats: A cadaveric study.

The intranasal route enables direct delivery of multiple substances from the nose to the brain, through olfactory and trigeminal pathways, bypassing the blood-brain barrier and avoiding systemic absorption. Despite the potential of this route, the various administration approaches make data reproducibility and interpretation challenging, emphasizing the necessity to establish a consistent methodology. Considering this, the aim of our study was to assess and compare the distribution of two dye volumes (30 µl and 50 µl) in the nasal cavity of rat cadavers. We employed three distinct methods of intranasal delivery: nose drops, by pipette tip, or cannula inserted into the nasal cavity. The results indicated that for both volumes, using the nose drops and the pipette tip methods, the dye dispersion occurred mainly in the vestibule, respiratory and olfactory regions, without reaching the olfactory bulbs. Using the cannula method, the deposition predominantly occurred in the respiratory and olfactory regions, with the dye reaching 66.7% and 100% of the olfactory bulbs, respectively, to low and high volume. Furthermore, the results demonstrated differences between the two volumes, in the pharynx, larynx, trachea, septal window, and incisive papilla, where an increased dye presence was observed with the 50 µl instillation across all three methods. According to our results, the intranasal delivery with a cannula was the most effective method for dye deposition in the olfactory region. However, further studies in live animals will be necessary to determine and refine the administration method that consistently allows specific deposition in the olfactory system.

Alginate Beads with Encapsulated Bioactive Substances from Mangifera indica Peels as Promising Peroral Delivery Systems.

Since various bioactive substances are unstable and can degrade in the gastrointestinal tract, their stabilization is crucial. This study aimed to encapsulate mango peel extract (MPE) into edible alginate beads using the ionotropic gelation method for the potential oral delivery of bioactive substances. Mango peels, generally discarded and environmentally harmful, are rich in health-promoting bioactive substances. The alginate beads were examined for entrapment efficiency, particle size, morphology, thermal stability, physiochemical interactions, release profile under gastrointestinal conditions, and antibacterial efficacy. The study demonstrated the successful encapsulation of MPE with an efficiency of 63.1%. The in vitro release study showed the stability of the alginate beads in simulated gastric fluid with a maximum release of 45.0%, and sustained, almost complete release (99.4%) in simulated intestinal fluid, indicating successful absorption into the human body. In both fluids, the MPE release followed first-order kinetics. Encapsulation successfully maintained the antibacterial properties of MPE, with significant inhibitory activity against pathogenic intestinal bacteria. This is the first study on MPE encapsulation in alginate beads, presenting a promising oral delivery system for high-added-value applications in the food industry for dietary supplements, functional foods, or food additives. Their production is sustainable and economical, utilizing waste material and reducing environmental pollution.