PLGA Nanoparticles Research Articles

Dual action tofacitinib-loaded PLGA nanoparticles alleviate colitis in an IBD mouse model.

Inflammatory bowel disease (IBD) affects over 7 million people worldwide and significant side effects are associated with current therapies such as tofacitinib citrate (TFC), which is linked to increased risks of malignancy and congestive heart issues. To mitigate these systemic adverse effects, localised drug delivery via nano-sized carriers to inflamed gut tissues represents a promising approach. Herein, we aimed to optimise the synthesis of nanoparticles (NPs) using a low molecular weight grade of Poly(lactic-co-glycolic acid) (PLGA) 50:50 loaded with TFC. This approach leverages the dual anti-inflammatory action of TFC and the local production of anti-inflammatory short-chain fatty acids from the degradation of PLGA by colonic gut microbiota. NPs were produced by nanoprecipitation and characterised for their drug release profile in vitro. The efficacy of the enhanced PLGA-TFC NPs was then tested in a C57BL/6 DSS colitis mouse model. The release profile of TFC from the enhanced PLGA NPs showed a 40% burst release within the first hour, followed by up to 80% drug release in the colonic environment. Notably, the degradation of PLGA by colonic gut microbiota did not significantly influence TFC release. In the mouse model, neither PLGA NPs alone nor TFC alone showed significant effects on weight loss compared to the TFC-loaded PLGA NPs, emphasising the enhanced efficacy potential of the combined formulation. Altogether, these results suggest a promising role of NP delivery systems in enhancing TFC efficacy, marking a significant step towards reducing dosage and associated side effects in IBD treatment. This study underscores the potential of PLGA-TFC NPs in providing targeted and effective therapy for IBD.

Nanoconjugate Carrying pH-Responsive Transferrin Receptor-Targeted Hesperetin Triggers Triple-Negative Breast Cancer Cell Death through Oxidative Attack and Assemblage of Pro-Apoptotic Proteins.

Triple-negative breast cancer (TNBC) is recognized as a major aggressive subtype of breast cancer due to its expeditious worsening growth, extensive metastatic capability, and recalcitrance to standard current treatments. Hesperetin (HSP), a natural bioflavonoid from citrus fruits, demonstrates pronounced anticancer efficacy, but its hydrophobicity limits its clinical development. The present study reports the fabrication of a biocompatible and pH-responsive transferrin (TF) receptor-targeted HSP-loaded poly(lactic-co-glycolic acid) (PLGA) nanobioconjugate (PLGA-HSP-TF NPs) and the exploration of its in vitro and in vivo antineoplastic potential. PLGA nanoparticles (NPs), PLGA-HSP NPs, and PLGA-HSP-TF NPs were synthesized and characterized by DLS, FTIR, FE-SEM, and 1H NMR spectroscopy. The stability and in vitro release profile of nanoparticles were inspected, and anticancer efficacy was scrutinized in terms of in vitro cytotoxicity, oxidative stress and apoptosis biomarkers, and cell cycle arrest. In vivo tumor regression and host survival studies were executed in Ehrlich ascites carcinoma (EAC) cell-bearing Swiss albino mice. The drug uptake of highly stable PLGA-HSP-TF NPs was accomplished effectively in MDA-MB-231 cells and showed the pH-dependent intracellular release of HSP, which generated excessive intracellular reactive oxygen species (ROS) that led to oxidative assault to the TNBC cells. This elevated ROS dropped the mitochondrial membrane potential and triggered apoptosis-mediated cell death by arresting the cell cycle at the G0/G1 phase. Furthermore, PLGA-HSP-TF NPs unveiled significant in vivo Ehrlich ascites carcinoma regression and host survival compared to free HSP with minimum toxicity at a minimum dose of 20 mg/kg body weight. The study divulges that PLGA-HSP-TF NPs may be an astounding anticancer nanocandidate for aggressive triple-negative breast cancer therapy.

Fabrication of apigenin and adenosine-loaded nanoparticles against doxorubicin-induced myocardial infarction by reducing inflammation and oxidative stress.

The study's goals are to fabricate PLGA nanoparticles (PNPs) loaded with apigenin (AP) and adenosine (AD) using a microfluidic preparation method to a standard emulsification method and investigate the possible heart-protective effects of AP-AD PNPs made using the emulsification method. Compared to microfluidics, the emulsification method fabricated small-size nanoparticles, which are better at encapsulating drugs, retaining more drugs, and having a low viscosity for the myocardial infarction (MI) injection. TheMI model was developed using SD rats injected under the skin with 85mg/kg doxorubicin (DOX) for 2 days. The metabolic results showed that our AP-AD PNPs accelerated the blood flow in rats with MI, which increased the amounts of AP and AD in the circulatory system. This led to significant improvements in the cardiac index and lower amounts of AST, LDH, and CK in the blood. A histopathological study using Hematoxylin&eosin, and TUNEL staining showed that cardiac function had improved and apoptosis had decreased. Moreover, tests that checked the amounts of IL-6, TNF-α, NO, GSH, MDA, and SOD showed that AP-AD PNPs may help treat MI by reducing oxidative stress and inflammation, making it a potentially useful therapeutic approach.

Optimising the production of PLGA nanoparticles by combining design of experiment and machine learning

Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable polymer in drug delivery and nanoparticle (NP) formulation due to its controlled drug release properties and safety profiles. Among the methods available for NP production, nanoprecipitation is distinguished by its simplicity and scalability. However, it requires careful optimisation to achieve the desired NP characteristics, making the process potentially lengthy and costly. This study aimed to assess and compare the predictive performance of Design of Experiments (DOE) and Machine Learning (ML) models for the optimisation of PLGA nanoparticle size and zeta potential produced by nanoprecipitation. Various ML methods were employed to predict particle size, with Extreme Gradient Boosting (XGBoost) identified as the best performing. The key finding is that integrating ML with DOE provides deeper insights into the dataset than either method alone. While ML outperformed DOE in predictive performance, as evidenced by lower root mean squared error values and higher coefficients of determination, both methods struggled to accurately predict zeta potential, generating models with high errors. However, ML proved more effective in identifying the parameters that most significantly influence NP size, even with a smaller DOE dataset. Combining DOE datasets with ML for parameter importance was particularly advantageous in situations where data is limited, offering superior predictive power and the potential to streamline experimental design and optimisation. These results suggest that the synergistic use of ML and DOE can lead to more robust feature analysis and improved optimisation outcomes, particularly for NP size. This integrated approach can enhance the accuracy of predictions and supports more efficient experimental design, streamlining nanoparticle production processes, especially under resource-constrained conditions.

Dexamethasone-loaded chitosan-decorated PLGA nanoparticles: a step forward in attenuating the COVID-19 cytokine storm?

This study aims to develop and characterize poly (lactic-co-glycolic acid) (PLGA) nanoparticles decorated with chitosan (CS) for the encapsulation of dexamethasone (DEX) (NP-DEX-CS), targeting improved efficacy in the treatment of severe acute respiratory syndrome (SARS) associated with COVID-19. The nanoparticles were systematically characterized for size, zeta potential (ZP), morphology, encapsulation efficiency, and in vitro drug release. Incorporation of CS resulted in significant modifications in the nanoparticles' physical properties, notably an increase in size (from 207.3 ± 6.7nm to 264.4 ± 4.4nm) and a shift in ZP to positive values (from -11.8 ±1.4mV to +30.0 ± 1,6mV). The NP-DEX-CS formulation achieved a high encapsulation efficiency (~79%) and a drug loading capacity of 6.53 ± 0.02%.In addition, the in vitro release rate of DEX from NP-DEX-CS was lower compared to undecorated nanoparticles, with a reduction from approximately 64% to 37% within 24h. Microscopy analyses revealed a smoother surface on the CS-decorated nanoparticles. FTIR and XRD analyses confirmed successful chitosan coating and DEX encapsulation. The CS coating enhanced the tolerability of J774.A1 cells to the nanoparticles, particularly evident at the highest concentration (400ug/mL), resulting in a cell viability ≥70%. Importantly, the NP-DEX-CS significantly reduced levels of nitric oxide and inflammatory cytokines (IL-1, IL-6, IL-12, and TNF-α). These findings suggest that CS-decorated PLGA nanoparticles hold promise as an effective dexamethasone delivery system for treating SARS related to COVID-19.

Development of Hybrid Implantable Local Release Systems Based on PLGA Nanoparticles with Applications in Bone Diseases.

The current strategy for treating osteomyelitis includes surgical procedures for complete debridement of the formed biofilm and necrotic tissues, systemic and oral antibiotic therapy, and the clinical use of cements and three-dimensional scaffolds as bone defect fillers and delivery systems for therapeutic agents. The aim of our research was to formulate a low-cost hybrid nanoparticulate biomaterial using poly(lactic-co-glycolic acid) (PLGA), in which we incorporated the therapeutic agent (ciprofloxacin), and to deposit this material on titanium plates using the matrix-assisted pulsed laser evaporation (MAPLE) technique. The deposited material demonstrated antibacterial properties, with all analyzed samples inhibiting the growth of tested bacterial strains, confirming the release of active substances from the investigated biocomposite. The poly(lactic-co-glycolic acid)-ciprofloxacin (PLGA-CIP) nanoparticle scaffolds displayed a prolonged local sustained release profile over a period of 45 days, which shows great promise in bone infections. Furthermore, the burst release ensures a highly efficient concentration, followed by a constant sustained release which allows the drug to remain in the implant-adjacent area for an extended time period.

Dual drug delivery systems based on natural and synthetic polymer particles for isoniazid and rifampicin vehiculization

AbstractThe purpose of this work is the design and characterization of novel systems based on micro and nanoparticles prepared from poly(lactic‐co‐glycolic) acid (PLGA), chitosan (CHT) and gelatin (GEL) for compartmentalization and dual release of rifampicin and isoniazid. The emulsion/evaporation method is employed for the preparation of PLGA based microparticles and nanoparticles. CHT and GEL are used for the preparation of microparticles by spray‐drying. Entrapment efficiencies are in the range of 35%–73% and 5%–29% for rifampicin and isoniazid in PLGA microparticles, respectively. For isoniazid GEL:CHT particles the entrapment efficiencies are within 82%–100%. Isoniazid shows a complete release at acid condition from GEL:CHT particles, while rifampicin release is maintained from GEL:CHT particles or displays an slightly increase from PLGA particles during buffer conditions. Antimycobacterial activity experiments show that the formulations present the ability to inhibit the bacterial growth in comparison with a control culture without treatment. Rifampicin PLGA and isoniazid GEL:CHT microparticles could be used for the preparation of a dual drug delivery system with each antibiotic in a single particulate compartment. GEL:CHT microparticles containing free isoniazid and rifampicin PLGA nanoparticles are a novel two compartment delivery system.

Pluronic F127/lecithin PLGA nanoparticles as carriers of monocyte-targeted jakinibs: a potential therapeutic platform.

Aim: In this study, PLGA nanoparticles (PNPs) emulsified in Pluronic F127 (F127)/Lecithin (LEC) were designed to load Itacitinib (ITA), a selective JAK1 inhibitor, for targeting human monocytes.Materials & methods: The physicochemical characteristics of empty and ITA-loaded F127/LEC PNPs were analyzed. The binding and internalization of NPs in leukocytes were evaluated. The effect of NPs on monocyte activation and JAK1 inhibition was assessed.Results: F127/LEC PNPs were selectively bound and internalized by monocytes, sparing other leukocytes. ITA-F127/LEC PNPs significantly dampened monocyte activation. They also inhibited the monocyte's ability to promote T-cell proliferation and inhibited proinflammatory cytokine production.Conclusion: ITA-loaded F127/LEC PNPs showed potential for monocyte-targeted therapy, offering new avenues for disease treatment.

Macrophage Membrane-Coated Nanoparticles for the Delivery of Natamycin Exhibit Increased Antifungal and Anti-Inflammatory Activities in Fungal Keratitis.

This study aims to explore the efficacy and safety of macrophage membrane-coated nanoparticles for the delivery of natamycin (NAT) in the therapy of fungal keratitis (FK). Macrophage membranes were isolated and identified by immunofluorescence staining (IFS). NAT was encapsulated into poly(lactic-co-glycolic acid) (PLGA). Fungal stimulated macrophage membranes (M1) or unstimulated membranes (M) were separately mixed and sonicated with PLGA nanoparticles. The biocompatible nanoparticles (PLGA-NAT, PLGA-NAT@M, and PLGA-NAT@M1) were characterized with zeta-sizer analysis, transmission electron microscopy (TEM), and Western blot. Drug encapsulation and loading efficiency and the release of NAT in the nanoparticles were detected by ultraviolet spectrophotometry. The cytotoxicity, ocular surface toxicity and irritability, and systemic safety of nanoparticles with different concentrations were assessed. In vitro, we examined the antifungal properties of the nanoparticles. The eye surface retention time, drug release, and curative effects on FK were evaluated in vitro and in vivo. IFS results showed the separation of the macrophage membrane and nucleus. The prepared nanoparticles had a typical "core-shell" structure and uniform nanometer size, and the membrane proteins were retained on the membrane allowing to exert functional effects of macrophage. The loading efficiencies of PLGA-NAT@M and PLGA-NAT@M1 were 7.6 and 6.7%, respectively. The encapsulation efficiencies of PLGA-NAT@M and PLGA-NAT@M1 were 51.2 and 41.5%, respectively. PLGA-NAT@M and PLGA-NAT@M1 could gradually release NAT and reduce the clearance of the ocular surface. Macrophage membranes enhanced the antifungal activity of PLGA-NAT. Furthermore, the membrane coated with macrophage increased the biocompatibility and decreased the corneal toxicity of nanoparticles. In vivo, PLGA-NAT@M1 significantly alleviated the severity of FK. In vitro, PLGA@M and PLGA@M1 reduced the protein levels of inflammatory cytokines after fungal stimulation. The prepared PLGA-NAT@M1 has good physical properties and biosafety. It could evade ocular surface clearance, release NAT gradually, and achieve high antifungal and anti-inflammatory efficiencies to FK. Macrophage membrane-coated nanoparticles clinically have high application potential to the treatment of FK.

A baculoviral gene and drug-eluting (GDES) stent to promote re-endothelialization and prevent restenosis caused by atherosclerosis

Abstract Background Coronary artery disease (CAD) is a prevalent condition affecting approximately one in every 20 individuals over the age of 20, resulting in significant health and economic burdens worldwide. Atherosclerosis, characterized by plaque buildup in the arteries, is a leading cause of CAD, involving endothelial dysfunction, inflammation, and smooth muscle cell hyperproliferation. The standard interventions for CAD, namely bare-metal stents (BMS) or drug-eluting stents (DES), often lead to complications such as blood clotting, inflammation, and arterial re-narrowing, necessitating further interventions and potentially leading to severe outcomes like heart failure, stroke, or death. Additionally, the TGFβ1 gene regulates SMC proliferation and ECM secretion, promoting endothelial cell proliferation, inhibiting smooth muscle cell hyperproliferation, reducing reactive oxygen species production. Purpose This innovative stent aims to mitigate complications associated with conventional stents by promoting endothelial health and preventing inflammation and hyperproliferation downstream. The purpose of this study is to design a new gene and drug eluting stent and evaluate their preclinical efficacy and safety in addressing some of the key limitations of currently available coronary stents. Methods The TGFβ1 expressing baculoviruses loaded PLGA nanoparticles are prepared by double emulsion solvent evaporation method. The formulated nanoparticles were characterized by their surface morphology, particle size, zeta potential, and in vitro release. Moreover, the designed nanoparticles undergo a further investigation for their therapeutic efficiency using cell lines. The GDES is synthesized by dip-coating a BMS into a solution containing Everolimus and genipin carrying baculoviruses expressing TGFβ1 in nanoparticles. The stent elutes the gene and drug over specific durations pertaining to a sustained release profile. The study assesses the functionality and safety of the GDES through in vitro and in vivo experiments, including cell culture studies and animal models. Results The PLGA nanoparticles at 115.3±1.4 nm with a polydipersity (pdi) index of 0.152 have a sustained release profile for the TGFβ1 expressing baculovirus. The findings demonstrate that the GDES effectively promotes endothelial health and prevents inflammation and hyperproliferation downstream. The expression of TGFβ1 facilitates the formation of a fully reconstituted endothelial lining, reducing the risk of complications. Additionally, the prolonged release of Everolimus prevents inflammation and the progression of neointimal hyperplasia. The stent coating and system exhibit non-cytotoxicity and hemocompatibility, ensuring safety during expansion and degradation over time. Overall, the combined action of gene and drug elution in the GDES shows promising results in addressing current complications associated with cardiovascular stents.

Berberine-loaded PLGA nanoparticles alleviate ulcerative colitis by targeting IL-6/IL-6R axis

AimsThe present study aims to develop a nano-delivery system that encapsulates berberine (BBR) into PLGA-based nanoparticles (BPL-NPs), to treat ulcerative colitis (UC). Furthermore, the therapeutic efficacy and molecular targeting mechanisms of BPL-NPs in the management of UC are thoroughly examined.MethodsEmulsion solvent-driven methods were used to self-assemble BBR and PLGA into nanoparticles, resulting in the development of the nano-delivery system (BPL-NPs). The therapeutic effectiveness of BPL-NPs was evaluated using a dextran sulfate sodium (DSS)-induced model of ulcerative colitis in mice and a lipopolysaccharide (LPS)-induced model of inflammation in THP-1 macrophages. The interaction between Mφs and NCM-460 cells was investigated using a co-culture system. The molecular targeting ability of BPL-NPs in the treatment of UC was validated through in vitro as well as in vivo experiments.ResultsThe BPL-NPs demonstrated a particle size of 184 ± 22.4 nm, enhanced dispersibility in deionized water, and a notable encapsulation efficiency of 31.1 ± 0.2%. The use of BPL-NPs clearly improved the clinical symptoms and pathological changes associated with UC in mice while also ensuring minimal toxicity. In addition, BPL-NPs improved intestinal epithelial cell apoptosis and enhanced the function of the intestinal barrier by inhibiting M1 Mφs infiltration and IL-6 signaling pathway in mice with UC. Furthermore, the BPL-NPs were found to selectively target the IL-6/IL-6R axis during the M1 Mφs-induced apoptosis of NCM460 cells.ConclusionThe BPL-NPs were confirmed to harbor anti-inflammatory effects both in vitro and in vivo, along with enhanced water solubility and bioactivity. In addition, the precise targeting of the IL-6/IL-6R axis was confirmed as the mechanism by which the BPL-NPs exerted therapeutic effects in UC, as demonstrated in both in vitro as well as in vivo studies.Graphical

Co-delivery of polyphyllin II and IR780 PLGA nanoparticles induced pyroptosis combined with photothermal to enhance hepatocellular carcinoma immunotherapy.

The clinical efficacy of immunotherapy for hepatocellular carcinoma (HCC) is significantly limited by the low immunogenicity of the tumor. Recent studies have revealed that both pyroptosis and photothermal therapy can effectively induce tumor immunogenic cell death (ICD) in liver cancer cells. Polyphyllin II (PPII), the major active component of Rhizoma Paridis, has been demonstrated for the first time to induce pyroptosis in tumor cells, while IR780 is activated by 808nm laser to transform light energy into heat energy, effectively eliminating tumor cells. However, both PPII and IR780 are afflicted with challenges such as low solubility and poor targeting, significantly limiting their utilization. To address these problems, the pyroptosis inducer PPII and photosensitizer IR780 were co-loaded in PLGA nanoparticles by precipitation method, and the aptamer AS1411 was modified on the surface of nanoparticles to construct the targeting nanoparticles (Apt/PPII/IR780-NPs). The nanoparticles exhibit a pH/NIR dual-response intelligent release feature, which realizes the targeted and controlled release of drugs in tumor site. Furthermore, it can rapidly release PPII to induce cell pyroptosis under laser irradiation, combining with IR780-based photothermal therapy exert a significant synergistic anti-tumor effect in vitro and in vivo. This process not only promotes maturation of DCs and activates effector T cells, thereby initiating adaptive immunity, but also generates enduring and effective immune memory. In addition, Apt/PPII/IR780-NPs significantly improved the Anti-PD-1 efficacy. In summary, chemo-photothermal therapy based on Apt/PPII/IR780-NPs can significantly enhance tumor ICD, which provides a promising new strategy for HCC immunotherapy.

Enhancing Vaccine Efficacy with Polyethylenimine-Modified Lovastatin-Loaded Nanoparticle Pickering Emulsion Adjuvant.

Despite the potent immunoadjuvant properties of mevalonate pathway inhibitors, their application is constrained by poor solubility and instability. In this study, we developed a cationic nanoparticle-stabilized Pickering emulsion loaded with lovastatin (Lov-PPE), using polyethylenimine (PEI)-modified PLGA nanoparticles and squalene as carriers. The system was prepared and tested by evaluating the physicochemical properties and adjuvant efficacy of the Lov-PPE. Lov-PPE/O demonstrated good particle size distribution and zeta potential, with an adsorption efficiency of up to 73.07%. The immunization results showed that Lov-PPE/O significantly promoted the production of OVA-specific IgG antibodies, activated CD4+ and CD8+ T cells, and induced a strong mixed Th1/2 immune response. Additionally, safety assessments indicated that Lov-PPE/O has good in vivo safety. This study demonstrates that the PEI-modified lovastatin PLGA nanoparticle Pickering emulsion (Lov-PPE) is an effective vaccine adjuvant capable of significantly enhancing humoral and cellular immune responses while possessing good safety, offering a new strategy for vaccine formulation development.

Exploring Nanocarriers for Boosting Entacapone Bioavailability: A Journey through System Characterization and Assessment of Toxicity and Pharmacological and 2D Permeability Paybacks.

Catechol-O-methyltransferase inhibitors (iCOMT), such as entacapone, have been successfully employed to treat tremor-related symptoms of Parkinson's disease. However, iCOMT has been associated with a short half-life and poor oral bioavailability. Nanobased drug delivery systems have often been used to overcome this type of setbacks. Therefore, entacapone was encapsulated in PEGylated poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) via a nanoprecipitation process, as well as in PEGylated nanostructured lipid carriers (NLCs) using a solvent emulsification/evaporation method. Both nanoformulations presented sub-200 nm populations, with zeta-potential (ZP) values close to -30 mV, and showed stability at different pHs, while maintaining their physicochemical properties mostly intact, presenting only a change in their superficial charge (ZP values), indicating their interaction. Both nanoformulations presented interaction with mucins, which anticipates good permeation and bioavailability for oral and topical administration. No cytotoxic effects were observed for lyophilized PLGA NPs encapsulating entacapone, in which 2-hydroxypropyl-ß-cyclodextrin (HPβCD) was used as a cryoprotectant at 3% concentration (HP-PLGA@Ent), in human hepatocellular carcinoma (HepG2), human neuroblastoma (SH-SY5Y), or human epithelial colorectal adenocarcinoma (Caco-2) cell lines. Conversely, NLCs encapsulating entacapone (W-NLCs@Ent) presented cytotoxic effects on the HepG2 cell line, likely due to intracellular lipid accumulation or storage. Both nanoformulations maintained a COMT inhibition effect in HepG2 cells, using 3-BTD as the COMT probe. An increase of entacapone permeability in both monolayer and coculture models (Caco-2 and Caco-2/HT29-MTX, respectively) was observed for the developed nanoformulations. Overall, this work shows that encapsulated entacapone in different nanocarriers could be a stimulating alternative to solve entacapone setbacks, since they improve its physicochemical properties and permeability while still maintaining the COMT inhibitory activity.

Curcumin attenuates smoking and drinking activated NF-κB/IL-6 inflammatory signaling axis in cervical cancer

BackgroundHigh-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated if smoking and/or drinking augment the molecular mechanisms of cervical carcinogenesis and defined a potential therapeutic approach for their attenuation.MethodsThe impact of benzo[a]pyrene (B[a]P) and/or ethanol (EtOH) exposure on cervical cancer cells was assessed by measuring changes in their cell migration and invasion characteristics. Expression of HPV16 E6/E7, NF-κB, cytokines, and inflammation mediators was determined using qRT-PCR, immunoblotting, ELISA, luciferase reporter assay, and confocal microscopy. Herein, we used curcumin (Cur), and PLGA nanoparticle formulation of curcumin (PLGA-Cur) and determined effectiveness of free Cur and PLGA-Cur formulation on smoking and drinking activated NF-κB/IL-6 mediated inflammatory signaling pathways using in vitro cervical cancer models.ResultsTreatments with B[a]P and/or EtOH altered the expression of HPV16 E6/E7 oncogenes and EMT markers in cervical cancer cells; it also enhanced migration and invasion. In addition, B[a]P and/or EtOH exposure promoted inflammation pathways through TNF-α and NF-κB signaling, leading to IL-6 upregulation and activation of VEGF. The molecular effects caused by B[a]P and/or EtOH exposure were effectively attenuated by curcumin (Cur)/PLGA-Cur treatment.ConclusionsThese data suggest a molecular link between smoking, drinking, and HPV infectivity in cervical carcinogenesis. In addition, attenuation of these effects by treatment with Cur/PLGA-Cur treatment, implies the role of curcumin in cervical cancer prevention and treatment.

Partial Protection of Goats against Haemonchus contortus Achieved with ADP-Ribosylation Factor 1 Encapsulated in PLGA Nanoparticles.

Haemonchus contortus (H. contortus), a nematode with global prevalence, poses a major threat to the gastrointestinal health of sheep and goats. In an effort to combat this parasite, a nanovaccine was created using a recombinant ADP-ribosylation factor 1 (ARF1) antigen encapsulated within poly lactic-co-glycolic acid (PLGA). This study aimed to assess the effectiveness of this nanovaccine in providing protection against H. contortus infection. Fifteen goats were randomly divided into three groups. The experimental group received two doses of the PLGA encapsulated rHcARF1 (rHcARF1-PLGA) nanovaccine on days 0 and 14. Fourteen days after the second immunization, both the experimental and positive control groups were challenged with 8000 infective larvae (L3) of H. contortus, while the negative control group remained unvaccinated and unchallenged. At the end of the experiment on the 63rd day, all animals were humanly euthanized. The results showed that the experimental group had significantly higher levels of sera IgG, IgA, and IgE antibodies, as well as increased concentrations of cytokines, such as IL-4, IL-9, IL-17, and TGF-β, compared to the negative control group after immunization. Following the L3 challenge, the experimental group exhibited a 47.5% reduction in mean eggs per gram of feces (EPG) and a 55.7% reduction in worm burden as compared to the positive control group. These findings indicate that the nanovaccine expressing rHcARF1 offers significant protective efficacy against H. contortus infection in goats. The results also suggest the need for more precise optimization of the antigen dose or a reassessment of the vaccination regimen. Additionally, the small sample size limits the statistical rigor and the broader applicability of the findings.

An Updated Review Summarizing the Anticancer Potential of Poly(Lactic-co-Glycolic Acid) (PLGA) Based Curcumin, Epigallocatechin Gallate, and Resveratrol Nanocarriers.

The utilization of nanoformulations derived from natural products for the treatment of many human diseases, including cancer, is a rapidly developing field. Conventional therapies used for cancer treatment have limited efficacy and a greater number of adverse effects. Hence, it is imperative to develop innovative anticancer drugs with superior effectiveness. Among the diverse array of natural anticancer compounds, resveratrol, curcumin, and epigallocatechin gallate (EGCG) have gained considerable attention in recent years. Despite their strong anticancer properties, medicinally significant phytochemicals such as resveratrol, curcumin, and EGCG have certain disadvantages, such as limited solubility in water, stability, and bioavailability problems. Encapsulating these phytochemicals in poly(lactic-co-glycolic acid) (PLGA), a polymer that is nontoxic, biodegradable, and biocompatible, is an effective method for delivering medication to the tumor location. In addition, PLGA nanoparticles can be modified with targeting molecules to specifically target cancer cells, thereby improving the effectiveness of phytochemicals in fighting tumors. Combining plant-based medicine (phytotherapy) with nanotechnology in a clinical environment has the potential to enhance the effectiveness of drugs and improve the overall health outcomes of patients. Therefore, it is crucial to have a comprehensive understanding of the different aspects and recent advancements in using PLGA-based nanocarriers for delivering anticancer phytochemicals. This review addresses the most recent advancements in PLGA-based delivery systems for resveratrol, EGCG, and curcumin, emphasizing the possibility of resolving issues related to the therapeutic efficacy and bioavailability of these compounds.

Li-Fraumeni Syndrome in Breast Cancer: Development of Theranostic Probes on Variation of P53

Li-Fraumeni Syndrome (LFS) is a hereditary condition characterized by a high predisposition to various cancers due to mutations in the p53 protein. Effectively targeting and treating this syndrome requires early detection and personalized treatment according to one’s specific nucleotide sequence. With the use of various forms of theranostics, LFS can be treated, increasing life expectancy; however, there is no absolute cure that could immediately end this syndrome. This paper delves into three different theranostic approaches: Gendicine (rAd-p53), Phesgo, and gold nanoshell poly(D, L-lactic-co-glycolic acid) nanoparticles (PLGA NPs). While each approach has limitations, PLGA nanoparticles exhibit advantages that outweigh their drawbacks, making it an attractive solution. This proposal will describe improvements to PLGA nanoparticles, which are a promising area of research for the development of new LFS treatments.

Silk fibroin/chitosan thiourea hydrogel scaffold with vancomycin and quercetin-loaded PLGA nanoparticles for treating chronic MRSA osteomyelitis in rats

Chronic osteomyelitis presents significant treatment challenges, necessitating an efficient system for infection elimination and bone repair. This study developed a natural hydrogel scaffold using silk fibroin (SF) and chitosan thiourea (CST), incorporating vancomycin (VC) and quercetin (QC) loaded PLGA nanoparticles (NPs) for dual-purpose treatment. SF/CST hydrogel scaffolds exhibited homogeneous porosity and smaller interconnected pore size than pure SF and pure CST hydrogel scaffolds. Optimal PLGA/QC NPs measured 206 nm in size, displayed spherical morphology, had uniform distribution, and achieved 87 % QC loading. The release study showed sustained long-term release of VC and QC from the hydrogel scaffolds for over 20 days. Biocompatibility tests indicated that hydrogel scaffolds promoted osteoblast adhesion without cytotoxicity, with QC-containing scaffolds enhancing osteoblast growth. Antibacterial tests confirmed retained VC activity against methicillin-resistant Staphylococcus aureus (MRSA) in SF/CST. An experimental study assessed the efficacy of the hydrogel scaffolds in a MRSA-infected rat osteomyelitis model. Radiographic scores demonstrated a significant reduction for SF/CST-VC-PLGA/QC NPs compared to control, indicating reduced osteomyelitis effects. Macroscopic evaluations showed notable reductions in gross pathological effects for VC-containing groups. Histopathological assessments revealed significantly lower osteomyelitis scores and higher healing scores in the SF/CST-VC-PLGA/QC NPs, with reduced inflammatory cell infiltration and more organized connective tissue formation. In conclusion, SF/CST-VC-PLGA/QC NPs is an effective dual drug delivery system for osteomyelitis treatment, demonstrating significant antibacterial activity, enhanced bone regeneration, and reduced infection rate.

Formulation development, characterization, and evaluation of sorafenib-loaded PLGA-chitosan nanoparticles.

The basic purpose of this work was to develop environmentally friendly, biodegradable, and biocompatible polymeric nanoparticles of sorafenib that can effectively release the desired drug in a customized and controlled manner for targeting hepatocellular carcinoma. The solvent evaporation technique was employed for the synthesis of sorafenib-loaded PLGA-chitosan nanoparticles, followed by various experimental specifications and compatibility studies using poloxamer 407 as the stabilizer. The best nanoparticles thus synthesized were selected to be used for cytotoxicity investigations through in vitro and in vivo assessments. For the in vitro drug release tests, the dialysis bag diffusion technique was used. For both chitosan nanoparticles and PLGA loaded with sorafenib, a biphasic release pattern was found, exhibiting a protracted release lasting 10 days after a 24-h burst release. As experimental animals, rabbits were utilized to evaluate different in vivo pharmacokinetic properties of the selected formulations. Plasma samples were extracted with acetonitrile and analyzed through the developed HPLC method. Pharmacokinetic parameters such as AUC0-t, Cmax MRT, Vd, and half-life (t1/2) were enhanced significantly (p ≤ 0.001), while clearance was considerably decreased (p ≤ 0.001) for the chosen synthesized nanoparticles in contrast to the commercially accessible sorafenib formulation (Nexavar®). The cytotoxicity of the reference drug and sorafenib-loaded PLGA and chitosan nanoparticles was calculated by performing an MTT assay against HepG2 cell lines. The developed polymeric sorafenib nanoformulations possess the appropriate physicochemical properties, better targeting, surface morphology, and prolonged release kinetics. The pharmacokinetic parameters were improved significantly when the results were compared with commercially available sorafenib formulations.