Biological Barriers Research Articles

Advanced Oral Drug Delivery Systems for Combating and Preventing Paediatric Periodontal Disease

: The oral route is the most common route of administration of drugs. Over 90% of all the available marketed pharmaceutical products are oral formulations. Oral drugs are used in different courses of treatment including the prevention of tooth decay. Tooth decay is the permanent damage of the enamel which leads to the formation of cavities. It can be prevented with good oral hygiene and enough fluorides in the body. Fluorides can be administered both topically (toothpastes) and systemically (supplements). Fluoride supplements fall under oral drug delivery systems. They come in the form of tablets, lozenges, and liquids. However, challenges are faced when it comes to oral drug delivery in children. The development of paediatric drugs is a difficult undertaking since many pharmaceutically active compounds have low water solubility, instability, or an unpleasant taste. Children are unable to tolerate bitter or unpleasant- tasting formulations, as well as huge pills and capsules. Due to various biological, biochemical, and physical barriers faced by oral drug delivery systems, new approaches have been developed to address these challenges such as the application of nanotechnology in drug development. Jellies for oral administration on the other hand are a new approach for the delivery of drugs with bitter tastes as well as for age groups such as children and elders. They are clear, translucent, or non-greasy semisolid products that can be used both externally and internally. In-depth, aspects of these factors will be discussed in this review paper including oral dosage forms for paediatrics, tooth decay and its pathogenesis, preventive measures and setbacks of each measure as well as the future perspectives.

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.

PLASTAMINATION: Outcomes on the Central Nervous System and Reproduction.

Environmental exposures to non-biodegradable and biodegradable plastics are unavoidable. Microplastics (MPs) and nanoplastics (NPs) from the manufacturing of plastics (primary sources) and the degradation of plastic waste (secondary sources) can enter the food chain directly or indirectly and, passing biological barriers, could target both the brain and the gonads. Hence, the worldwide diffusion of environmental plastic contamination (PLASTAMINATION) in daily life may represent a possible and potentially serious risk to human health. This review provides an overview of the effects of non-biodegradable and the more recently introduced biodegradable MPs and NPs on the brain and brain-dependent reproductive functions, summarizing the molecular mechanisms and outcomes on nervous and reproductive organs. Data from in vitro, ex vivo, non-mammalian and mammalian animal models and epidemiological studies have been reviewed and discussed. MPs and NPs from non-biodegradable plastics affect organs, tissues and cells from sensitive systems such as the brain and reproductive organs. Both MPs and NPs induce oxidative stress, chronic inflammation, energy metabolism disorders, mitochondrial dysfunction and cytotoxicity, which in turn are responsible for neuroinflammation, dysregulation of synaptic functions, metabolic dysbiosis, poor gamete quality, and neuronal and reproductive toxicity. In spite of this mechanistic knowledge gained from studies of non-biodegradable plastics, relatively little is known about the adverse effects or molecular mechanisms of MPs and NPs from biodegradable plastics. The neurological and reproductive health risks of MPs/NPs exposure warrant serious consideration, and further studies on biodegradable plastics are recommended.

Green Nanotechnology Through Papain Nanoparticles: Preclinical in vitro and in vivo Evaluation of Imaging Triple-Negative Breast Tumors.

Recent advancements in nanomedicine and nanotechnology have expanded the scope of multifunctional nanostructures, offering innovative solutions for targeted drug delivery and diagnostic agents in oncology and nuclear medicine. Nanoparticles, particularly those derived from natural sources, hold immense potential in overcoming biological barriers to enhance therapeutic efficacy and diagnostic accuracy. Papain, a natural plant protease derived from Carica papaya, emerges as a promising candidate for green nanotechnology-based applications due to its diverse medicinal properties, including anticancer properties. This study presents a novel approach in nanomedicine and oncology, exploring the potential of green nanotechnology by developing and evaluating technetium-99m radiolabeled papain nanoparticles (99mTc-P-NPs) for imaging breast tumors. The study aimed to investigate the efficacy and specificity of these nanoparticles in breast cancer models through preclinical in vitro and in vivo assessments. Papain nanoparticles (P-NPs) were synthesized using a radiation-driven method and underwent thorough characterization, including size, surface morphology, surface charge, and cytotoxicity assessment. Subsequently, P-NPs were radiolabeled with technetium-99m (99mTc), and in vitro and in vivo studies were conducted to evaluate cellular uptake at tumor sites, along with biodistribution, SPECT/CT imaging, autoradiography, and immunohistochemistry assays, using breast cancer models. The synthesized P-NPs exhibited a size mean diameter of 9.3 ± 1.9 nm and a spherical shape. The in vitro cytotoxic activity of native papain and P-NPs showed low cytotoxicity in HUVEC, MDA-MB231, and 4T1 cells. The achieved radiochemical yield was 94.2 ± 3.1% that were sufficiently stable (≥90%) for 6 h. The tumor uptake achieved in the 4T1 model was 2.49 ± 0.32% IA/g at 2h and 1.51 ± 0.20% IA/g at 6h. In the spontaneous breast cancer model, 1.19 ± 0.20% IA/g at 2h and 0.86 ± 0.31% IA/g at 6h. SPECT/CT imaging has shown substantial tumor uptake of the new nanoradiopharmaceutical and clear tumor visualization. 99mTc-P-NPs exhibited a high affinity to tumoral cells confirmed by ex vivo autoradiography and immunohistochemistry assays. The findings underscore the potential of green nanotechnology-driven papain nanoparticles as promising agents for molecular imaging of breast and other tumors through SPECT/CT imaging. The results represent a substantial step forward in the application of papain nanoparticles as carriers of diagnostic and therapeutic radionuclides to deliver diagnostic/therapeutic payloads site-specifically to tumor sites for the development of a new generation of nanoradiopharmaceuticals.

Intelligent drugs based on notch protein remodeling: a defensive targeting strategy for tumor therapy

In the process of tumor treatment, systemic drug administration is hindered by biological barriers, leading to the retention of a large number of drug molecules in healthy tissues and causing unavoidable side effects. The precise deployment of drugs at the tumor site is expected to alleviate this phenomenon. Here, we take endostatin and Her2 (+) tumors as examples and develop an intelligent drug with simple “wisdom” by endowing mesenchymal stem cells (MSCs) with an intelligent response program (iMSCEndostatin). It can autonomously perceive and distinguish tumor cells from non-tumor cells, establishing a logical connection between tumor signals and drug release. Enable it to selectively deploy drugs at the tumor site, thereby locking the toxicity of drugs at the tumor site. Unlike traditional aggressive targeting strategies that aim to increase drug concentration at the lesion, intelligent drugs are more inclined to be defensive strategies that prevent the presence of drugs in healthy tissues.

Adaptive Size Evolution of an MOFs-in-MOF Nanovehicle for Enhanced Nucleus-Targeted Tumor Chemotherapy.

A metal-organic frameworks (MOFs)-in-MOF nanovehicle (160 nm), which was constructed with newly prepared ultrasmall Cu(I)Cu(II)-BTC MOFs (UCMs, 2.95 nm) loaded with doxorubicin (DOX) and a nuclear localization signal (NLS) peptide as multicores (UCMDNs) and ZIF-8 as the shell MOF, was proposed to cross layers of biological barriers with adaptive size evolution capacity for achieving efficient nucleus-targeted drug delivery. It first enhanced tumor tissue penetration through its larger nanosize effect. Then the acidic tumor environment made the ZIF-8 shell degrade, releasing small-sized UCMDNs to enter into the cell and into the nucleus under the guidance of NLS. Furthermore, due to the distinct surface structural characteristics of UCMs, UCMDNs remained stable in the cytoplasm and collapsed in the nucleus due to the DOX-DNA interaction to deliver DOX precisely. It showed superior performance in the nucleus-directed delivery of DOX (delivery efficiency up to 56.7%) and a high tumor growth inhibition rate (96.4%), offering promising prospects in tumor chemotherapy.

Biosurfactant Nanomicelles and Peptide Integration: Novel Approaches to Targeted Gene Delivery in Colon Cancer Treatment.

A notable breakthrough in the treatment of colon cancer involves the utilisation of a cutting-edge drug delivery technology known as biosurfactant-derived nanomicelles. These nanomicelles, composed of natural biosurfactant molecules, possess the distinct capability to enclose pharmaceuticals or genetic material, such as DNA, siRNA, or mRNA, within spherical formations. With a size ranging from 10 to 100 nanometers, these nanomicelles exhibit precision targeting capabilities towards colon cancer cells, hence minimising the occurrence of side effects typically associated with treatment. Upon being specifically targeted, the nanomicelles liberate their cargo into cancer cells, resulting in enhanced therapy efficacy. This novel strategy utilises the specific attributes of the tumour microenvironment to administer precise and focused treatment. These nanomicelles improve the absorption by cells and reduce harm to healthy tissues by imitating important nutrients or utilising compounds that specifically target tumours. Furthermore, the incorporation of stimuli-responsive components allows for regulated medication release in reaction to the acidic environment seen in tumours. The review focuses on examining the use of biosurfactants and natural peptides in nanomicellar carriers as ways to fight against colon cancer. Folate-coated nanomicelles incorporating curcumin facilitate precise gene delivery, while the partnership of biosurfactants, such as surfactin from Bacillus subtilis and natural peptides, enables the transportation of particular cyclopeptides into the tumour network. Peptides, similar to bombesin, direct nanomicelles to specific places, while peptides based on curcumin control the release of medicinal substances. While preclinical investigations demonstrate promise, obstacles remain in formulation and regulatory issues. However, biosurfactant-based nanomicelles, particularly folate-coated carriers loaded with curcumin, show tremendous potential in overcoming biological barriers and delivering medicines efficiently to colon cancer cells.

Dendrimers-Novel Therapeutic Approaches for Alzheimer's Disease.

Dendrimers are covalently bonded globular nanostructures that may be used in the treatment of Alzheimer's disease (AD). Nowadays, AD therapies are focused on improving cognitive functioning and not causal treatment. However, this may change with the use of dendrimers, which are being investigated as a drug-delivery system or as a drug per se. With their ability to inhibit amyloid formation and their anti-tau properties, they are a promising therapeutic option for AD patients. Studies have shown that dendrimers may inhibit amyloid formation in at least two ways: by blocking fibril growth and by breaking already existing fibrils. Neurofibrillary tangles (NFTs) are abnormal filaments built by tau proteins that can be accumulated in the cell, which leads to the loss of cytoskeletal microtubules and tubulin-associated proteins. Cationic phosphorus dendrimers, with their anti-tau properties, can induce the aggregation of tau into amorphous structures. Drug delivery to mitochondria is difficult due to poor transport across biological barriers, such as the inner mitochondrial membrane, which is highly negatively polarized. Dendrimers may be potential nanocarriers and increase mitochondria targeting. Another considered use of dendrimers in AD treatment is as a drug-delivery system, for example, carbamazepine (CBZ) or tacrine. They can also be used to transport siRNA into neuronal tissue and to carry antioxidants and anti-inflammatory drugs to act protectively on the nervous system.

Nanoparticle-Based Therapies for Neurotropic Viral Infections: Mechanisms, Challenges, and Future Prospects.

Neurotropic viral infections pose a significant challenge due to their ability to target the central nervous system and cause severe neurological complications. Traditional antiviral therapies face limitations in effectively treating these infections, primarily due to the blood-brain barrier, which restricts the delivery of therapeutic agents to the central nervous system. Nanoparticle-based therapies have emerged as a promising approach to overcome these challenges. Nanoparticles offer unique properties that facilitate drug delivery across biological barriers, such as the blood-brain barrier, and can be engineered to possess antiviral activities.

Recent Review on Biological Barriers and Host-Material Interfaces in Precision Drug Delivery: Advancement in Biomaterial Engineering for Better Treatment Therapies.

Preclinical and clinical studies have demonstrated that precision therapy has a broad variety of treatment applications, making it an interesting research topic with exciting potential in numerous sectors. However, major obstacles, such as inefficient and unsafe delivery systems and severe side effects, have impeded the widespread use of precision medicine. The purpose of drug delivery systems (DDSs) is to regulate the time and place of drug release and action. They aid in enhancing the equilibrium between medicinal efficacy on target and hazardous side effects off target. One promising approach is biomaterial-assisted biotherapy, which takes advantage of biomaterials' special capabilities, such as high biocompatibility and bioactive characteristics. When administered via different routes, drug molecules deal with biological barriers; DDSs help them overcome these hurdles. With their adaptable features and ample packing capacity, biomaterial-based delivery systems allow for the targeted, localised, and prolonged release of medications. Additionally, they are being investigated more and more for the purpose of controlling the interface between the host tissue and implanted biomedical materials. This review discusses innovative nanoparticle designs for precision and non-personalised applications to improve precision therapies. We prioritised nanoparticle design trends that address heterogeneous delivery barriers, because we believe intelligent nanoparticle design can improve patient outcomes by enabling precision designs and improving general delivery efficacy. We additionally reviewed the most recent literature on biomaterials used in biotherapy and vaccine development, covering drug delivery, stem cell therapy, gene therapy, and other similar fields; we have also addressed the difficulties and future potential of biomaterial-assisted biotherapies.

Intertumoral and intratumoral barriers as approaches for drug delivery and theranostics to solid tumors using stimuli-responsive materials.

The solid tumors provide a series of biological barriers in cellular microenvironment for designing drug delivery methods based on advanced stimuli-responsive materials. These intertumoral and intratumoral barriers consist of perforated endotheliums, tumor cell crowding, vascularity, lymphatic drainage blocking effect, extracellular matrix (ECM) proteins, hypoxia, and acidosis. Triggering opportunities have been drawn for solid tumor therapies based on single and dual stimuli-responsive drug delivery systems (DDSs) that not only improved drug targeting in deeper sites of the tumor microenvironments, but also facilitated the antitumor drug release efficiency. Single and dual stimuli-responsive materials which are known for their lowest side effects can be categorized in 17 main groups which involve to internal and external stimuli anticancer drug carriers in proportion to microenvironments of targeted solid tumors. Development of such drug carriers can circumvent barriers in clinical trial studies based on their superior capabilities in penetrating into more inaccessible sites of the tumor tissues. In recent designs, key characteristics of these DDSs such as fast response to intracellular and extracellular factors, effective cytotoxicity with minimum side effect, efficient permeability, and rate and location of drug release have been discussed as core concerns of designing paradigms of these materials.

Trends on Nanomedicines as Novel therapeutics Approach in Targeting Nociceptors for Relieving Pain.

An important sensation that warns of potential harm to a specific area of the body is pain. The prevalence of pain-related conditions globally is a significant and growing public health issue. Chronic pain affects an estimated 1.5 billion people worldwide, with prevalence rates varying by region and demographic factors. Along with diabetes, cardiovascular disease, and cancer, pain is among the most frequent medical diseases. Opioid analgesics are the mainstay of current pain therapies, which are ineffective. Opioid addiction and its potentially fatal side effects necessitate novel treatment strategies. Nanotechnology offers potential advantages in pain management by enabling targeted drug delivery, which can enhance the efficacy and reduce the side effects of analgesic medications. Additionally, nanoparticles can be designed to release drugs in a controlled manner, improving pain relief duration and consistency. This approach also allows for the delivery of therapeutics across biological barriers, potentially enhancing treatment outcomes for chronic pain conditions. Nanomedicine enables sensitive and focused treatments with fewer side effects than existing clinical pain medicines; it is worth exploring as a potential solution to these problems. Furthermore, medication delivery systems that use nanomaterials are being used to treat pain. Whether it's the distribution of a single medication or a combination of therapies, this review seeks to summarise the ways in which drug delivery systems based on nanomaterials can be utilised to successfully treat and alleviate pain. For the purpose of writing this paper, we consulted several online libraries, including Pubmed, Science Direct, Pubmed Prime, and the Cochrane Library, to gather fresh and up-to-date material. This overview delves into the ins and outs of pain's pathophysiology, the present state of pain treatment, potential new pain treatment targets, and the various initiatives that have been launched and are still in the works to address pain with nanotechnology. Recent developments in nanomaterials-based scavenging, gene therapy for pain aetiology, and nanoparticle-based medicine delivery for side effect reduction are highlighted. Analgesics have been further covered in our discussion on FDA-approved pharmaceuticals and clinical advancements.

Plastic particle impacts on the cardiovascular system and angiogenesis potential.

The extensive application of plastics in different sectors such as packaging, building, textiles, consumer products, and several industries has increased in recent years. Emerging data have confirmed that plastic wastes and segregates are problematic issues in aquatic and terrestrial ecosystems. The decomposition of plastic particles (PPs) leads to the release of microplastics (MPs) and nanoplastics (NPs) into the surrounding environment and entry of these particles will be problematic in unicellular and multicellular creatures. It was suggested that PPs can easily cross all biological barriers and reach different organs, especially the cardiovascular system, with the potential to modulate several molecular pathways. It is postulated that the direct interaction of PPs with cellular and subcellular components induces genotoxicity and cytotoxicity within the cardiovascular system. Meanwhile, being inert carriers, PPs can intensify the toxicity of other contaminants inside the cardiovascular system. Here, in this review article, several underlying mechanisms related to PP toxicity in the cardiovascular system were discussed in detail.

Advancements in Cancer Therapeutics: Current Paradigms in Applying Biodegradable Polymer Nanoparticles for Enhanced Management

Abstract: The development of novel colloidal formulations that can regulate the pharmacological and biological properties of medications has been made possible by the developments of nanotechnology. Biodegradable nanoparticles were exploited as drug delivery methods because of their high bioavailability, improved encapsulation, controlled release, and less toxic characteristics. Over the past few decades, a variety of synthetic polymers have been investigated for application in nanomedicine, particularly in drug delivery systems. Drug delivery polymers need to be environmentally friendly, biodegradable, and biocompatible. As they have the ability to provide targeted delivery to a specified site, polymeric nanoparticles have the potential to increase the effectiveness of cancer therapies significantly. It is possible to modify the physical and chemical characteristics of polymers to provide delivery across the many biological barriers needed to reach different cell subsets. The use of biodegradable polymers as nanocarriers is particularly appealing since these materials can be developed to show triggered functionality at certain locations or activated by an external source in addition to degrading under physiological circumstances. Biodegradable polymers can be developed as easy drug-delivery systems that specifically target the tumour microenvironment. This is because these nanomedicines can directly target cancer cells, as well as blood vessels that supply the nutrition and oxygen required for tumour growth and immune cells that support anti-cancer immunotherapy. With the advancements in nanotechnology-based drug delivery systems for pharmaceutical applications, it is exciting to examine and highlight the significance of polymeric nanocarrier systems for drug delivery in chemotherapy.

(Invited) Tuning Chirality of Graphene Quantum Dots to Empower Medical Imaging and Theranostic Applications

Chiral nanostructures from metals and semiconductor, including graphene-based materials, are increasingly recognized for their potential in polarization-sensitive optoelectronics. Particularly, graphene quantum dots (GQDs) modified with L/D amino acids exhibit unique chiral properties due to edge-specific interactions, offering new possibilities in biomedicine. Our study delves into the interaction of these chiral nanomaterials with biological systems, revealing significant implications for their application in biology and medicine. We discovered that attaching L/D amino acid moieties to GQDs induces nanoscale chirality by helical buckling, influenced by the chiral interactions at the graphene edges. The chirality of GQDs affects their interaction at the nanoscale with cells and tissues. Molecular dynamics simulations show that D-GQDs are more likely to accumulate within cellular membranes compared to L-GQDs. Additionally, experiments on chiral GQD permeation through lipid membranes of extracellular vesicles demonstrated that optimizing chirality via ligand tuning and GQD size can significantly enhance their permeation efficiency into lipid bilayers, exceeding 80%. Leveraging this enhanced transmembrane transport, chiral GQDs have been applied in imaging and efficient drug loading for therapeutic extracellular vesicles. Furthermore, we explored how GQD chirality affects transport in tumor-like cellular spheroids. The results indicate that L-GQDs exhibit a 1.7 times higher apparent diffusion coefficient than D-GQDs, enhancing their transport into these spheroids. In summary, our research underscores the importance of controlling and engineering GQD chirality. This approach not only enhances the transport of drug carriers through biological barriers but also opens new avenues for advanced imaging and theranostic applications.

Peptide ligands for the universal purification of exosomes by affinity chromatography.

Exosomes are gaining prominence as vectors for drug delivery, vaccination, and regenerative medicine. Owing to their surface biochemistry, which reflects the parent cell membrane, these nanoscale biologics feature low immunogenicity, tunable tissue tropism, and the ability to carry a variety of payloads across biological barriers. The heterogeneity of exosomes' size and composition, however, makes their purification challenging. Traditional techniques, like ultracentrifugation and filtration, afford low product yield and purity, and jeopardizes particle integrity. Affinity chromatography represents an excellent avenue for exosome purification. Yet, current affinity media rely on antibody ligands whose selectivity grants high product purity, but mandates the customization of adsorbents for exosomes with different surface biochemistry while their binding strength imposes elution conditions that may harm product's activity. Addressing these issues, this study introduces the first peptide affinity ligands for the universal purification of exosomes from recombinant feedstocks. The peptides were designed to (1) possess promiscuous biorecognition of exosome markers, without binding process-related contaminants and (2) elute the product under conditions that safeguard product stability. Selected ligands SNGFKKHI and TAHFKKKH demonstrated the ability to capture of exosomes secreted by 14 cell sources and purified exosomes derived from HEK293, PC3, MM1, U87, and COLO1 cells with yields of up to 80% and up-to 50-fold reduction of host cell proteins (HCPs) upon eluting with pH gradient from 7.4 to 10.5, recommended for exosome stability. SNGFKKHI-Toyopearl resin was finally employed in a two-step purification process to isolate exosomes from HEK293 cell fluids, affording a yield of 68% and reducing the titer of HCPs to 68 ng/mL. The biomolecular and morphological features of the isolated exosomes were confirmed by analytical chromatography, Western blot analysis, transmission electron microscopy, nanoparticle tracking analysis.

Comparison of colostrum and milk extracellular vesicles small RNA cargo in water buffalo

Recently, much interest has been raised for the characterization of signaling molecules carried by extracellular vesicles (EVs), which are particularly enriched in milk (mEVs). Such interest is linked to the capability of EVs to cross biological barriers, resist acidification in the gastric environment, and exert modulation of the immune system, mainly through their microRNA (miRNA) content. We characterized the small-RNA cargo of colostrum EVs (colosEVs) and mEVs from Italian Mediterranean buffalo through next generation sequencing. Colostrum (first milking after birth) and milk (day 50 of lactation) were sampled from seven subjects from five farms. ColosEVs and mEVs were subjected to morphological characterization, followed by high-depth sequencing of small RNA libraries produced from total RNA. The main difference was the amount of EV in the two samples, with colostrum showing 10 to 100-fold higher content than milk. For both matrices, miRNA was the most abundant RNA species (95% for colosEVs and 96% for mEVs) and three lists were identified: colosEV-specific, mEV-specific and shared most expressed. Gene ontology (GO) enrichment analysis on miRNA targets highlighted many terms related to the epigenetic, transcriptional and translational regulations across the three lists, with a higher number of enriched terms for colosEV-specific miRNAs. Terms specific to colosEVs were related to “cell differentiation” and “microvillus assembly”, while for mEV “cardiac and blood vessel development” and “mitochondria” emergerd. Immune modulation terms were found for both sample-specific miRNAs. Overall, both matrices carry a similar molecular message in terms of biological processes potentially modulated into receiving cells, but there is significant difference in the abundance, with colostrum containing much more EVs than milk. Moreover, colosEVs carry molecules involved in signal transduction, cell cycle and immune response, as for mEVs and EVs of other previously characterized species, but with a special enrichment for miRNAs with epigenetic regulation capacities. These beneficial characteristics of colosEVs and mEVs are essential for the calf and could also be exploited for the therapeutic purposes in humans, although further studies are necessary to measure the sanitization treatment impact on EV conservation, especially in buffalo where milk is consumed almost exclusively after processing.

An investigation of nano- and micron-sized carriers based on calcium carbonate and polylactic acid for oral administration of siRNA

ABSTRACT Background Oral delivery of small interfering RNAs (siRNAs) draws significant attention, but the gastrointestinal tract (GIT) has many biological barriers that limit the drugs’ bioavailability. The aim of this work was to investigate the potential of micro- and nano-sized CaCO3 and PLA carriers for oral delivery of siRNA and reveal a relationship between the physicochemical features of these carriers and their biodistribution. Research design and methods In vitro stability of carriers was investigated in simulated gastric and intestinal fluids. Toxicity and cellular uptake were investigated on Caco-2 cells. The biodistribution profiles of the developed CaCO3 and PLA carriers were examined using different visualization methods, including SPECT, fluorescence imaging, radiometry, and histological analysis. The delivery efficiency of siRNA loaded carriers was investigated both in vitro and in vivo. Results Micro-sized carriers were accumulated in the stomach and later localized in the colon tissues. The nanoscale particles (100–250 nm) were distributed in the colon tissues. nPLA was also detected in small intestine. The developed carriers can prevent siRNA from premature degradation in GIT media. Conclusion Our results reveal how the physicochemical properties of the particles, including their size and material type can affect their biodistribution profile and oral delivery of siRNA.

Biorobotic Drug Delivery for Biomedical Applications.

Despite extensive efforts, current drug-delivery systems face biological barriers and difficulties in bench-to-clinical use. Biomedical robotic systems have emerged as a new strategy for drug delivery because of their innovative diminutive engines. These motors enable the biorobots to move independently rather than relying on body fluids. The main components of biorobots are engines controlled by external stimuli, chemical reactions, and biological responses. Many biorobot designs are inspired by blood cells or microorganisms that possess innate swimming abilities and can incorporate living materials into their structures. This review explores the mechanisms of biorobot locomotion, achievements in robotic drug delivery, obstacles, and the perspectives of translational research.

In Vitro Studies to Evaluate the Intestinal Permeation of an Ursodeoxycholic Acid-Conjugated Oligonucleotide for Duchenne Muscular Dystrophy Treatment.

Delivery represents a major hurdle to the clinical advancement of oligonucleotide therapeutics for the treatment of disorders such as Duchenne muscular dystrophy (DMD). In this preliminary study, we explored the ability of 2'-O-methyl-phosphorothioate antisense oligonucleotides (ASOs) conjugated with lipophilic ursodeoxycholic acid (UDCA) to permeate across intestinal barriers in vitro by a co-culture system of non-contacting IEC-6 cells and DMD myotubes, either alone or encapsulated in exosomes. UDCA was used to enhance the lipophilicity and membrane permeability of ASOs, potentially improving oral bioavailability. Exosomes were employed due to their biocompatibility and ability to deliver therapeutic cargo across biological barriers. Exon skipping was evaluated in the DMD myotubes to reveal the targeting efficiency. Exosomes extracted from milk and wild-type myotubes loaded with 5'-UDC-3'Cy3-ASO and seeded directly on DMD myotubes appear able to fuse to myotubes and induce exon skipping, up to ~20%. Permeation studies using the co-culture system were performed with 5'-UDC-3'Cy3-ASO 51 alone or loaded in milk-derived exosomes. In this setting, only gymnotic delivery induced significant levels of exon skipping (almost 30%) implying a possible role of the intestinal cells in enhancing delivery of ASOs. These results warrant further investigations to elucidate the delivery of ASOs by gymnosis or exosomes.