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International Journal of Nanomedicine 2024The design of delivery tools that efficiently transport drugs into cells remains a major challenge in drug development for most pathological conditions. Triple-negative...
INTRODUCTION
The design of delivery tools that efficiently transport drugs into cells remains a major challenge in drug development for most pathological conditions. Triple-negative breast cancer (TNBC) is a very aggressive subtype of breast cancer with poor prognosis and limited effective therapeutic options.
PURPOSE
In TNBC treatment, chemotherapy remains the milestone, and doxorubicin (Dox) represents the first-line systemic treatment; however, its non-selective distribution causes a cascade of side effects. To address these problems, we developed a delivery platform based on the self-assembly of amphiphilic peptides carrying several moieties on their surfaces, aimed at targeting, enhancing penetration, and therapy.
METHODS
Through a single-step self-assembly process, we used amphiphilic peptides to obtain nanofibers decorated on their surfaces with the selected moieties. The surface of the nanofiber was decorated with a cell-penetrating peptide (gH625), an EGFR-targeting peptide (P22), and Dox bound to the cleavage sequence selectively recognized and cleaved by MMP-9 to obtain on-demand drug release. Detailed physicochemical and cellular analyses were performed.
RESULTS
The obtained nanofiber (NF-Dox) had a length of 250 nm and a diameter of 10 nm, and it was stable under dilution, ionic strength, and different pH environments. The biological results showed that the presence of gH625 favored the complete internalization of NF-Dox after 1h in MDA-MB 231 cells, mainly through a translocation mechanism. Interestingly, we observed the absence of toxicity of the carrier (NF) on both healthy cells such as HaCaT and TNBC cancer lines, while a similar antiproliferative effect was observed on TNBC cells after the treatment with the free-Dox at 50 µM and NF-Dox carrying 7.5 µM of Dox.
DISCUSSION
We envision that this platform is extremely versatile and can be used to efficiently carry and deliver diverse moieties. The knowledge acquired from this study will provide important guidelines for applications in basic research and biomedicine.
Topics: Doxorubicin; Triple Negative Breast Neoplasms; Humans; Nanofibers; Cell Line, Tumor; Female; Drug Delivery Systems; Cell-Penetrating Peptides; Drug Liberation; Cell Survival; Peptides; Antibiotics, Antineoplastic; ErbB Receptors; Matrix Metalloproteinase 9; Drug Carriers
PubMed: 38911501
DOI: 10.2147/IJN.S453958 -
International Journal of Nanomedicine 2024The relentless pursuit of effective cancer diagnosis and treatment strategies has led to the rapidly expanding field of nanotechnology, with a specific focus on... (Review)
Review
The relentless pursuit of effective cancer diagnosis and treatment strategies has led to the rapidly expanding field of nanotechnology, with a specific focus on nanocomposites. Nanocomposites, a combination of nanomaterials with diverse properties, have emerged as versatile tools in oncology, offering multifunctional platforms for targeted delivery, imaging, and therapeutic interventions. Nanocomposites exhibit great potential for early detection and accurate imaging in cancer diagnosis. Integrating various imaging modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence imaging, into nanocomposites enables the development of contrast agents with enhanced sensitivity and specificity. Moreover, functionalizing nanocomposites with targeting ligands ensures selective accumulation in tumor tissues, facilitating precise imaging and diagnostic accuracy. On the therapeutic front, nanocomposites have revolutionized cancer treatment by overcoming traditional challenges associated with drug delivery. The controlled release of therapeutic agents from nanocomposite carriers enhances drug bioavailability, reduces systemic toxicity, and improves overall treatment efficacy. Additionally, the integration of stimuli-responsive components within nanocomposites enables site-specific drug release triggered by the unique microenvironment of the tumor. Despite the remarkable progress in the field, challenges such as biocompatibility, scalability, and long-term safety profiles remain. This article provides a comprehensive overview of recent developments, challenges, and prospects, emphasizing the transformative potential of nanocomposites in revolutionizing the landscape of cancer diagnostics and therapeutics. In Conclusion, integrating nanocomposites in cancer diagnosis and treatment heralds a new era for precision medicine.
Topics: Humans; Nanocomposites; Neoplasms; Animals; Antineoplastic Agents; Drug Delivery Systems; Magnetic Resonance Imaging; Contrast Media; Nanomedicine; Tomography, X-Ray Computed; Drug Carriers
PubMed: 38911500
DOI: 10.2147/IJN.S471360 -
International Journal of Nanomedicine 2024Ginsenoside Rg3 (Rg3) and Panax notoginseng saponins (PNS) can be used for ischemic stroke treatment, however, the lack of targeting to the ischemic region limits the...
PURPOSE
Ginsenoside Rg3 (Rg3) and Panax notoginseng saponins (PNS) can be used for ischemic stroke treatment, however, the lack of targeting to the ischemic region limits the therapeutic effect. To address this, we leveraged the affinity of macrophage membrane proteins for inflamed brain microvascular endothelial cells to develop a macrophage membrane-cloaked liposome loaded with Rg3 and PNS (MM-Lip-Rg3/PNS), which can precisely target brain lesion region through intranasal administration.
METHODS
MM-Lip-Rg3/PNS was prepared by co-extrusion method and was performed by characterization, stability, surface protein, and morphology. The cellular uptake, immune escape ability, and blood-brain barrier crossing ability of MM-Lip-Rg3/PNS were studied in vitro. The in vivo brain targeting, biodistribution and anti-ischemic efficacy of MM-Lip-Rg3/PNS were evaluated in MACO rats, and we determined the diversity of the nasal brain pathway through the olfactory nerve blockade model in rats. Finally, the pharmacokinetics and brain targeting index of MM-Lip-Rg3/PNS were investigated.
RESULTS
Our results indicated that MM-Lip-Rg3/PNS was spherical with a shell-core structure. MM-Lip-Rg3/PNS can avoid mononuclear phagocytosis, actively bind to inflammatory endothelial cells, and have the ability to cross the blood-brain barrier. Moreover, MM-Lip-Rg3/PNS could specifically target ischemic sites, even microglia, increase the cumulative number of drugs in the brain, improve the inflammatory environment of the brain, and reduce the infarct size. By comparing olfactory nerve-blocking rats with normal rats, it was found that there are direct and indirect pathways for nasal entry into the brain. Pharmacokinetics demonstrated that MM-Lip-Rg3/PNS exhibited stronger brain targeting and prolonged drug half-life.
CONCLUSION
MM-Lip-Rg3/PNS might contribute to the accumulation of Rg3 and PNS in the ischemic brain area to improve treatment efficacy. This biomimetic nano-drug delivery system provides a new and promising strategy for the treatment of ischemic stroke.
Topics: Animals; Liposomes; Administration, Intranasal; Ischemic Stroke; Rats; Male; Ginsenosides; Blood-Brain Barrier; Macrophages; Drug Delivery Systems; Rats, Sprague-Dawley; Tissue Distribution; Brain; Biomimetic Materials; Saponins; Mice
PubMed: 38911498
DOI: 10.2147/IJN.S458656 -
BMJ Open Diabetes Research & Care Jun 2024To assess the efficacy of a chitosan-based gel (ChitoCare) for the treatment of non-healing diabetic foot ulcers (DFUs). (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
To assess the efficacy of a chitosan-based gel (ChitoCare) for the treatment of non-healing diabetic foot ulcers (DFUs).
RESEARCH DESIGN AND METHODS
Forty-two patients with chronic DFUs were randomized to the ChitoCare or placebo gel for a 10-week treatment period and 4-week follow-up. The primary study end point was the rate of complete wound closure at week 10, presented as relative rate.
RESULTS
Thirty patients completed the 10-week treatment and 28 completed the 4-week follow-up. The ChitoCare arm achieved 16.7% complete wound closure at week 10 vs 4.2% in the placebo arm (p=0.297), 92.0% vs 37.0% median relative reduction in wound surface area from baseline at week 10 (p=0.008), and 4.62-fold higher likelihood of achieving 75% wound closure at week 10 (p=0.012). Based on the results of the Bates-Jensen Wound Assessment Tool, the wound state at week 10 and the relative improvement from the baseline were significantly better (median 20 vs 24 points, p=0.018, and median 29.8% vs 3.6%, p=0.010, respectively).
CONCLUSIONS
ChitoCare gel increased the rate of the DFU healing process. Several secondary end points significantly favored ChitoCare gel.
TRIAL REGISTRATION NUMBER
NCT04178525.
Topics: Humans; Chitosan; Diabetic Foot; Female; Male; Middle Aged; Gels; Wound Healing; Aged; Follow-Up Studies; Treatment Outcome; Chronic Disease; Double-Blind Method; Prognosis
PubMed: 38909998
DOI: 10.1136/bmjdrc-2024-004195 -
Scientific Reports Jun 2024Frequent and variant infections are caused by the virtue of opportunistic fungi pathogens. Candidiasis, aspergillosis, and mucormycosis are pathogenic microorganisms...
Frequent and variant infections are caused by the virtue of opportunistic fungi pathogens. Candidiasis, aspergillosis, and mucormycosis are pathogenic microorganisms that give rise to vast fungal diseases that alternate between moderate to fatal in severity. The use of fluconazole as an antifungal drug was limited due to the acquired resistance in some types of Candida and other fungal species. This study aims to consolidate fluconazole's biological effectiveness against several pathogenic fungi. Six active monoterpenes (MTs) of carvacrol, linalool, geraniol, α-terpinene, citronellal, and nerolidol were selected and encapsulated in nanostructure lipid carrier (NLC) with (NLC-Flu-MTs) and/without (NLC-MTs) fluconazole in one nanoformulation to determine if they will act synergistically or not? The synthesized nanoformulation NLC-Flu-MTs and NLC-MTs exhibited very good particle size of 144.5 nm and 138.6 nm for size and zeta potential values of (- 23.5 mV) and (- 20.3 mV), respectively. Transmission electron microscope investigation confirmed that the synthesized NLCs have regular and spherical shape. The abundance and concentration of the six released monoterpenes were determined, as a novel approach, using GC-MS with very good results and validity. In-vitro antifungal screening was done before and after nano co-delivery against seven pathogenic, and aggressive fungi of Candida tropicalis, Candida krusei, Candida glabrata, Geotrichum Candidum, Candidaalbicans, Aspergillus Niger, and mucor circinelloides. Inhibition Zone diameter (IZD) and the minimum inhibitory concentration (MIC) were measured. Nanoformulations NLC-Flu-MTs and NLC-MTs manifested potential and unique biological susceptibility against all the tested microorganisms with reduced (MIC) values, especially against Candida Tropicalis (MIC = 0.97 µg/ml) which represents 16-fold of the value shown by NLC-MTs (MIC = 15.6 µg/ml) and 64-fold of fluconazole free before nanoformulation (MIC = 62.5 µg/ml). The efficiency of nanomaterials, particularly NLC-Flu-MTs, has become evident in the diminishing value of MIC which affirmed the synergism between fluconazole and the other six monoterpenes.
Topics: Antifungal Agents; Fluconazole; Microbial Sensitivity Tests; Monoterpenes; Nanostructures; Lipids; Drug Synergism; Drug Carriers; Particle Size; Candida
PubMed: 38909063
DOI: 10.1038/s41598-024-63149-x -
Journal of Applied Biomaterials &... 2024Atomization is a treatment method to make inhaled liquids into aerosols and transport them to target organs in the form of fog or smoke. It has the advantages of...
Atomization is a treatment method to make inhaled liquids into aerosols and transport them to target organs in the form of fog or smoke. It has the advantages of improving the bioavailability of drugs, being painless, and non-invasive, and is now widely used in the treatment of lung and oral lesions. Aerosol inhalation as the route of administration of therapeutic proteins holds significant promise due to its ability to achieve high bioavailability in non-invasive pathways. Currently, a great number of therapeutic proteins such as alpha-1 antitrypsin and Dornase alfa are effective. Recombinant humanized collagen type III (rhCol III) as a therapeutic protein is widely used in the biomedical field, but atomization is not a common route of administration for rhCol III, presenting great potential for development. However, the structural stability of recombinant humanized collagen after atomization needs further investigation. This study demonstrated that the rhCol III subjected to atomization through compressed air had retained its original molecular weights, triple helical structures, and the ability to promote cell adhesion. In other words, the rhCol III can maintain its stability after undergoing atomization. Although more research is required to determine the efficacy and safety of the rhCol III after atomization, this study can lay the groundwork for future research.
Topics: Recombinant Proteins; Humans; Collagen Type III; Aerosols
PubMed: 38907595
DOI: 10.1177/22808000241261904 -
BMC Ophthalmology Jun 2024Retinopathy of prematurity (ROP) is a proliferative disorder of the developing retina. Intravitreal bevacizumab injection (IVB) is an emerging treatment for severe forms...
BACKGROUND
Retinopathy of prematurity (ROP) is a proliferative disorder of the developing retina. Intravitreal bevacizumab injection (IVB) is an emerging treatment for severe forms of ROP, which does not restrict the visual field in comparison to laser therapy. The present study aimed to determine and evaluate the risk factors for ROP recurrence following IVB injection.
MATERIALS AND METHODS
In this retrospective study, 98 eyes of 49 infants with ROP who had received IVB injections as the primary treatment for type 1 ROP are included.
RESULTS
Fifty-four eyes (55.1%) had aggressive retinopathy of prematurity (A-ROP), and forty-four (44.9%) had Stage III Plus ROP in Zone II. ROP recurred in 13 eyes (13.26%) of 8 infants. The mean period between IVB and the ROP recurrence was 8.08 (95% CI:5.32-10.83) weeks. The infants who had ROP recurrence had lower birth weight (P value = 0.002), lower postmenstrual age at IVB injection (P value = 0.001), lower IVB injection gap period from birth (P value = 0.044), higher oxygen therapy requirement rate after IVB injection (P value < 0.001, OR:19.0) and higher oxygen therapy duration (P value = 0.006). The ROP severity, gestational age at birth, and diet were not statistically different between the recurrence and complete regression groups. Out of 13 eyes treated with laser photocoagulation because of ROP relapse, macula dragging occurred in one eye, and all the cases met the complete regression.
CONCLUSION
Low birth weight and oxygen therapy are the most important risk factors for ROP relapse, which requires meticulous oxygen treatment guidelines for premature infants.
Topics: Humans; Retinopathy of Prematurity; Bevacizumab; Intravitreal Injections; Retrospective Studies; Angiogenesis Inhibitors; Female; Male; Recurrence; Infant, Newborn; Gestational Age; Vascular Endothelial Growth Factor A; Risk Factors; Infant; Follow-Up Studies; Infant, Premature
PubMed: 38907228
DOI: 10.1186/s12886-024-03528-0 -
Nature Communications Jun 2024Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is closely associated with various malignancies. Considering the complex life cycle of EBV,...
Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is closely associated with various malignancies. Considering the complex life cycle of EBV, developing vaccines targeting key entry glycoproteins to elicit robust and durable adaptive immune responses may provide better protection. EBV gHgL-, gB- and gp42-specific antibodies in healthy EBV carriers contributed to sera neutralizing abilities in vitro, indicating that they are potential antigen candidates. To enhance the immunogenicity of these antigens, we formulate three nanovaccines by co-delivering molecular adjuvants (CpG and MPLA) and antigens (gHgL, gB or gp42). These nanovaccines induce robust humoral and cellular responses through efficient activation of dendritic cells and germinal center response. Importantly, these nanovaccines generate high levels of neutralizing antibodies recognizing vulnerable sites of all three antigens. IgGs induced by a cocktail vaccine containing three nanovaccines confer superior protection from lethal EBV challenge in female humanized mice compared to IgG elicited by individual NP-gHgL, NP-gB and NP-gp42. Importantly, serum antibodies elicited by cocktail nanovaccine immunization confer durable protection against EBV-associated lymphoma. Overall, the cocktail nanovaccine shows robust immunogenicity and is a promising candidate for further clinical trials.
Topics: Animals; Epstein-Barr Virus Infections; Antibodies, Neutralizing; Herpesvirus 4, Human; Humans; Female; Mice; Antibodies, Viral; Glycoproteins; Nanoparticles; Adjuvants, Immunologic; Lymphoma; Nanovaccines
PubMed: 38906867
DOI: 10.1038/s41467-024-49546-w -
PloS One 2024The primary objective of this investigation was to assess the viability of free and encapsulated Lactobacillus plantarum probiotics in mango juice and under simulated...
The primary objective of this investigation was to assess the viability of free and encapsulated Lactobacillus plantarum probiotics in mango juice and under simulated gastrointestinal conditions. Specifically, the probiotics were encapsulated using sodium alginate and alginate-soy protein isolate through the internal gelation method, and the obtained probiotics were characterized for various attributes. Both free and encapsulated probiotics were exposed to challenging conditions, including thermal stress, low temperature, and simulated gastrointestinal conditions. Additionally, both types of probiotics were incorporated into mango juice, and their survival was monitored over a 28-day storage period. Following viability under simulated gastrointestinal conditions, the count of free and encapsulated probiotic cells decreased from initial levels of 9.57 log CFU/mL, 9.55 log CFU/mL, and 9.53 log CFU/mL, 9.56 log CFU/mL to final levels of 6.14 log CFU/mL, 8.31 log CFU/mL, and 6.24 log CFU/mL, 8.62 log CFU/mL, respectively. Notably, encapsulated probiotics exhibited a decrease of 1.24 log CFU and 0.94 log CFU, while free cells experienced a reduction of 3.43 log CFU and 6.24 log CFU in mango juice over the storage period. Encapsulated probiotics demonstrated higher viability in mango juice compared to free probiotics throughout the 28-day storage period. These findings suggest that mango juice can be enriched with probiotics to create a health-promoting beverage.
Topics: Probiotics; Lactobacillus plantarum; Alginates; Microbial Viability; Gastrointestinal Tract; Mangifera; Gels; Fruit and Vegetable Juices; Soybean Proteins
PubMed: 38905169
DOI: 10.1371/journal.pone.0303091 -
Zhongguo Ying Yong Sheng Li Xue Za Zhi... Jun 2024The human immune system plays a pivotal role in protecting the body against pathogens, maintaining homeostasis, and preventing disease. Immunomodulation, the process of... (Review)
Review
The human immune system plays a pivotal role in protecting the body against pathogens, maintaining homeostasis, and preventing disease. Immunomodulation, the process of regulating immune responses, is crucial for optimal health. In recent years, there has been growing interest in natural remedies for immune system modulation, driven by the recognition of their potential efficacy and safety profiles. This project aims to investigate the immunomodulatory effects of drumstick leaves tablets, derived from Moringa oleifera, a plant known for its rich nutritional and medicinal properties. The study will explore the potential of drumstick leaves tablets to modulate immune responses through in vitro and in vivo experiments. Through comprehensive analysis of the immunomodulatory properties of drumstick leaves tablets, this project aims to contribute to our understanding of natural remedies for immune system modulation. The findings could have significant implications for the development of novel therapeutic interventions aimed at enhancing immune function and improving human health.
Topics: Moringa oleifera; Plant Leaves; Immunomodulating Agents; Tablets; Animals; Immunologic Factors; Mice; Humans; Drugs, Chinese Herbal
PubMed: 38902996
DOI: 10.62958/j.cjap.2024.004