PLGA NPs Research Articles

The Evaluation of Anti-Osteoclastic Activity of the Novel Calcium Hydroxide Biodegradable Nanoparticles as an Intracanal Medicament

ABSTRACT Objective: The present investigation looked into PLGA micron-sized particles or NPs, loaded with calcium hydroxide for canal disinfecting processes which have antimicrobial properties, given the significant rejection probabilities related to these kinds of treatments. Methodology: The MIC and inhibitory growing zones (n = 5) were found using the broth dilution and agar diffusion tests, accordingly. Employing confocal microscopy and live/dead labelling, cell viability was evaluated (n = 5). ANOVA was used to evaluate, and post hoc analysis came next. Results: Ca(OH)2 NPs showed a minimum inhibitory concentration of 5 μg/mL for Fn and 10 μg/mL for Pg and Ef (P < 0.001), following a 24-hour incubation period. Conclusion: To sum up, Ca(OH)2-contained PLGA NPs show encouraging ability to kill microbes during canal cleaning treatments.

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.

Engineering of layer-by-layer acetate-coated paclitaxel loaded poly(lactide-co-glycolide) acid nanoparticles for prostate cancer therapy- in vitro

It is hypothesized that layer-by-layer acetate-coated Paclitaxel-loaded PLGA nanoparticles (F2) can be engineered to potentiate the effectiveness of Paclitaxel (PTX) on LNCaP, a human prostate cancer cell line. The core of the layer-by-layer NPs is formed by nanoprecipitation, and the shell of the NPs is engineered using the sodium acetate's unique coating mechanism and surface-active properties. The resulting nanoformulation physicochemical properties are characterized by Fourier Transform Infra-Red (FTIR), Differential Scanning Calorimetry (DSC) Transmission Electron Microscopy (TEM), NanoSight NS300, spectrophotometry, Korsmeyer-Peppas model, respectively. The NP's cytotoxicity on LNCaP is assessed by MTS assay. The DSC and the FTIR confirm SA's coating of the NPs. The particle's mean diameters (PMD) are 89.4±2.3- to 114.4±7.6 nm. The TEM shows a unique multilayer and spherical nanoparticle. The encapsulation efficiency of commonly PTX-loaded PLGA NPs (F1) and F2 are 84.37±2.71% and 86.74±2.22, respectively. The drug transport mechanism of F1 and F2 is anomalous transport and case II, respectively. F2 follows a zero-order release mechanism. The cell viability is 45.08±2.18% and 60.17±4.72% when LNCaP is treated with 10 µg/mL of F2 and F1, respectively, after 48 hours of exposure. F2 and F1 cell growth inhibition are dose-dependent. This unique process of engineering the layer-by-layer NPs will provide new horizons for developing future innovative nanoparticles for targeted prostate cancer therapy.

Combination chemotherapy via poloxamer 188 surface-modified PLGA nanoparticles that traverse the blood–brain–barrier in a glioblastoma model

The effect of chemotherapy for anti-glioblastoma is limited due to insufficient drug delivery across the blood–brain–barrier. Poloxamer 188-coated nanoparticles can enhance the delivery of nanoparticles across the blood–brain–barrier. This study presents the design, preparation, and evaluation of a combination of PLGA nanoparticles (PLGA NPs) loaded with methotrexate (P-MTX NPs) and PLGA nanoparticles loaded with paclitaxel (P-PTX NPs), both of which were surface-modified with poloxamer188. Cranial tumors were induced by implanting C6 cells in a rat model and MRI demonstrated that the tumors were indistinguishable in the two rats with P-MTX NPs + P-PTX NPs treated groups. Brain PET scans exhibited a decreased brain-to-background ratio which could be attributed to the diminished metabolic tumor volume. The expression of Ki-67 as a poor prognosis factor, was significantly lower in P-MTX NPs + P-PTX NPs compared to the control. Furthermore, the biodistribution of PLGA NPs was determined by carbon quantum dots loaded into PLGA NPs (P-CQD NPs), and quantitative analysis of ex-vivo imaging of the dissected organs demonstrated that 17.2 ± 0.6% of the NPs were concentrated in the brain after 48 h. The findings highlight the efficacy of combination nanochemotherapy in glioblastoma treatment, indicating the need for further preclinical studies.

Synergistic antifungal activity against Candida albicans between voriconazole and cyclosporine a loaded in polymeric nanoparticles

The goal of this work is to investigate if the synergistic antifungal activity between cyclosporine A, CsA, and voriconazole, VRZ, increases when both drugs are encapsulated in a nanocarrier as compared when they are free. The preparation and characterization of blank and VRZ and CsA loaded polymeric based PLGA nanoparticles (PLGA, PLGA-PEG, and PLGA+PEG) was a necessary previous step. Using the more suitable NPs, those of PLGA, the antifungal susceptibility tests performed with VRZ-loaded PLGA NPs, show no significant increase of the antifungal activity in comparison to that of free VRZ. However, the synergistic behavior found for the (VRZ+CsA)-loaded PLGA NPs was fourfold stronger than that observed for the two free drugs together. On the other hand, the investigation into the suppression of C. albicans biofilm formation showed that blank PLGA NPs inhibit the biofilm formation at high NPs concentrations. However, a minor effect or even a slight biofilm increase formation was observed at low and moderate NPs concentrations. Therefore, the enhancement of the biofilm inhibition found for the three tested treatments (CsA alone, VRZ alone, and VRZ+CsA) when comparing free and encapsulated drugs, within the therapeutic window, can be attributed to the drug encapsulation approach. Indeed, polymeric PLGA NPs loaded with CsA, VRZ, or VRZ+CsA are more effective at inhibiting the C. albicans biofilm growth than their free counterparts.

Development of α-Tocopherol Loaded PLGA Nanoparticles and Its Evaluation as a Novel Immune Adjuvant.

With the continuous development of preventive and therapeutic vaccines, traditional adjuvants cannot provide sufficient immune efficacy and it is of high necessity to develop safe and effective novel nanoparticle-based vaccine adjuvants. α-Tocopherol (TOC) is commonly used in oil-emulsion adjuvant systems as an immune enhancer, yet its bioavailability is limited by poor water solubility. This study aims to develop TOC-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TOC-PLGA NPs) to explore the potential of TOC-PLGA NPs as a novel nanoparticle-immune adjuvant. TOC-PLGA NPs are prepared by a nanoprecipitation method and their physicochemical properties are characterized. It is shown that TOC-PLGA NPs are 110.8nm, polydispersity indexvalue of 0.042, and Zeta potential of -13.26mV. The encapsulation efficiency and drug loading of NPs are 82.57% and 11.80%, respectively, and the cumulative release after 35days of in vitro testing reaches 47%. Furthermore, TOC-PLGA NPs demonstrate a superior promotion effect on RAW 264.7 cell proliferation compared to PLGA NPs, being well phagocytosed and also promoting antigen uptake by macrophages. TOC-PLGA NPs can strongly upregulate the expression of co-stimulatory surface molecules and the secretion of cytokines. In conclusion, TOC-PLGA NPs can be a novel vaccine adjuvant with excellent biocompatibility and significant immune-enhancing activity.

Comparison of cell delivery and cell membrane camouflaged PLGA nanoparticles in the delivery of shikonin for colorectal cancer treatment

Inspired by the "natural camouflage" strategy, cell-based biomimetic drug delivery systems (BDDS) have shown great potential in cancer therapy. Red blood cell (RBC) delivery vehicles and red blood cell membrane (RBCm)-camouflaged vehicles were commonly used strategies for drug delivery. We prepared shikonin-encapsulated PLGA nanoparticles (PLGA/SK) with different surface charges to obtain both RBC delivery and RBCm-camouflaged PLGA NPs. The physicochemical properties, in vivo circulation and antitumor effects of these biomimetic preparations were studied. Since the positive PLGA NPs may affect the morphology and function of RBCs, the biomimetic preparations prepared by the negative PLGA NPs showed better in vitro stability. However, positive PLGA NP-based biomimetic preparations exhibited longer circulation time and higher tumor region accumulation, leading to stronger anti-tumor effects. Meanwhile, the RBC delivery PLGA(+) NPs possessed better in vitro cytotoxicity, longer circulation time and higher tumor accumulation than RBCm-camouflaged PLGA(+) NPs. Collectively, RBC delivery vehicles possessed more potential than RBCm-camouflaged vehicles on drug delivery for tumor treatment, especially with positive NPs-loaded.

Synthesis of novel coumarin-triazole hybrids and first evaluation of the 4-phenyl substituted hybrid loaded PLGA nanoparticles delivery system to the anticancer activity

Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes in the last century, many studies are still being carried out to develop drugs with higher anticancer efficacy and lower level of side effects. Herein, we designed, synthesized, and characterized six novel coumarin-triazole hybrids, and evaluated for anticancer activity of the one with the highest potential against the breast cancer cell line, MCF-7 and human cervical cancer cell line, human cervical adenocarcinoma (HeLa). Compound 21 which was the coumarin derivative including phenyl substituent with the lowest IC50 value displayed the highest cytotoxicity against the studied cancer cell line. Furthermore, the potential use of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) prepared by the emulsifying solvent evaporation method as a platform for a drug delivery system was studied on a selected coumarin derivative 21. This coumarin derivative-loaded PLGA NPs were produced with an average size of 225.90 ± 2.96 nm, −16.90 ± 0.85 mV zeta potential, and 4.12 ± 0.90% drug loading capacity. The obtained 21-loaded PLGA nanoparticles were analyzed spectroscopically and microscopically with FT-IR, UV–vis, and scanning electron microscopy as well as thermogravimetric analysis, Raman, and x-ray diffraction. The in vitro release of 21 from the nanoparticles exhibited a controlled release profile just over one month following a burst release in the initial six hours and in addition to this a total release ratio of %50 and %85 were obtained at pH 7.4 and 5.5, respectively. 21-loaded PLGA nanoparticles displayed remarkably effective anticancer activity than 21. The IC50 values were determined as IC50 (21-loaded PLGA nanoparticles): 0.42 ± 0.01 mg ml−1 and IC50 (free 21 molecule): 5.74 ± 3.82 mg ml−1 against MCF-7 cells, and as IC50 (21-loaded PLGA nanoparticles): 0.77 ± 0.12 mg ml−1 and IC50 (free 21 molecule): 1.32 ± 0.31 mg ml−1 against HeLa cells after the incubation period of 24 h. Our findings indicated that triazole-substituted coumarins may be used as an anticancer agent by integrating them into a polymeric drug delivery system providing improved drug loading and effective controlled drug release.

Rescuing a Troubled Tolcapone with PEGylated PLGA Nanoparticles: Design, Characterization, and Hepatotoxicity Evaluation.

Tolcapone is an orally active catechol-O-methyltransferase (COMT) inhibitor used as adjuvant therapy in Parkinson's disease. However, it has a highly hepatotoxic profile, as recognized by the U.S. Food and Drug Administration. As a possible solution, nanoscience brought us several tools in the development of new functional nanomaterials with tunable physicochemical properties, which can be part of a solution to solve several drawbacks, including drug's short half-life and toxicity. This work aims to use PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles as a stable carrier with lower hydrodynamic size and polydispersity to encapsulate tolcapone in order to overcome its therapeutic drawbacks. Using the nanoprecipitation method, tolcapone-loaded nanoparticles with a DLC% of 5.7% were obtained (EE% of 47.0%) and subjected to a lyophilization optimization process to obtain a final shelf-stable formulation. Six different cryoprotectants in concentrations up to 10% (w/v) were tested. A formulation of PLGA nanoparticles with 3% hydroxypropyl-β-cyclodextrin (HPβCD) as a cryoprotectant (PLGA-HP@Tolc), presenting sub-200 nm sizes and low polydispersity (PdI < 0.200) was selected. Cytotoxicity assays, namely, MTT and SRB, were used to study the metabolic activity and cell density of tolcapone and PLGA-HP@Tolc-treated cells. In both assays, a hepatocarcinoma cell line (HepG2) growing in glucose or glucose-free media (galactose-supplemented medium) was used. The results demonstrated that the treatment with the PLGA-HP@Tolc formulation led to a decrease in cytotoxicity in comparison to free tolcapone-treated cells in both media tested. Moreover, the elected formulation also counteracted ATP-depletion and excessive ROS production induced by tolcapone. The results suggest that HPβCD might have a dual function in the formulation: cryoprotectant and anticytotoxic agent, protecting cells from tolcapone-induced damage. Using an in vitro COMT inhibition assay, the PLGA-HP@Tolc formulation demonstrated to inhibit COMT as efficiently as free tolcapone. Overall, the results suggest that tolcapone-loaded PLGA NPs could be an interesting alternative to free tolcapone, demonstrating the same in vitro efficacy in inhibiting COMT but with a safer cytotoxic profile.

The In Vivo Biological Fate of Protein Corona: A Comparative PET Study of the Fate of Soft and Hard Protein Corona in Healthy Animal Models.

Radiolabeling and nuclear imaging techniques are used to investigate the biodistribution patterns of the soft and hard protein corona around poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) after administration to healthy mice. Soft and hard protein coronas of 131I-labeled BSA or 131I-labeled serum are formed on PLGA NPs functionalized with either polyehtylenimine (PEI) or bovine serum albumin (BSA). The exchangeability of hard and soft corona is assessed in vitro by gamma counting exposing PLGA NPs with corona to non-labeled BSA, serum, or simulated body fluid. PEI PLGA NPs form larger and more stable coronas than BSA PLGA NPs. Soft coronas are more exchangeable than hard ones.The in vivo fate of PEI PLGA NPs coated with preformed 18F-labeled BSA hard and soft coronas is assessed by positron emission tomography (PET)following intravenous administration. While the soft corona shows a biodistribution similar to free 18F BSA with high activity in blood and kidney, the hard corona follows patterns characteristic of nanoparticles, accumulating in the lungs, liver, and spleen. These results show that in vivo fates of soft and hard corona are different, and that soft corona is more easily exchanged with proteins from the body, while hard corona is largely retained on the nanoparticle surface.

Aurothioglucose encapsulated nanoparticles fostered neuroprotection in streptozotocin-induced Alzheimer’s disease

Alzherimer’s disease (AD) is an age-dependent ubiquitous ailment worldwide with limited therapies that only alleviate the symptoms of AD but do not cure them entirely because of the restricted blood–brain barrier passage of the drug. Hence with new advanced technology, nanoparticles can offer an opportunity as the active candidate to overcome the above limitations. Aurothioglucose, a synthetic glucose derivative of the gold compound, has been clinically proven to be an effective anti-inflammatory drug for rheumatic arthritis. Recently, several scientific groups have developed gold nanoparticle preparations and tested them for the treatment of dementia. This study was planned to prepare the PLGA nanoparticles of aurothioglucose (ATG) and check the neuroprotective potential against STZ-induced AD in rats. The nanoparticles were prepared using the double emulsion solvent evaporation method and characterized for various parameters such as drug-excipient interaction, particle size, zeta potential, and morphology. Then, rats were injected STZ (3 mg/kg/i.c.v., days 1 and 3) and ATG (5 and 10 mg/kg/s.c.), ATG NPs (2.5 and 5 mg/kg/s.c.) and donepezil (2 mg/kg/p.o) from 15th to 29th day. Behavior parameters were performed using an actophotometer, MWM, and ORT. On the 30th day, all the animals were sacrificed, and the brains were isolated for estimating biochemical, neurochemical, and proinflammatory markers. It was observed that ATG NPs significantly restored all behavior and neurotransmitter alterations caused by STZ. Also, it increased antioxidant levels and decreased inflammatory cytokines significantly, then ATG alone. Thus, the study suggests that ATG loaded PLGA NPs could be used as a novel therapeutic strategy to slow the process of AD.

Spray Coating of Wood with Nanoparticles from Lignin and Polylactic Glycolic Acid Loaded with Thyme Essential Oils.

Ensuring the longevity of wooden constructions depends heavily on the preservation process. However, several traditional preservation methods involving fossil-based compounds have become outdated because they pose a significant risk to the environment and to human health. Therefore, the use of bio-based and bioactive solutions, such as essential oils, has emerged as a more sustainable alternative in protecting wood from biotic attacks. The entrapment of essential oils in polymeric carrier matrices provides protection against oxidation and subsequent degradation or rapid evaporation, which implies the loss of their biocidal effect. In this work, lignin as well as PLGA nanoparticles containing the essential oils from two different thyme species (Thymus capitatus and T. vulgaris) were applied on beech wood samples using spray coating. The prepared coatings were investigated using FTIR imaging, SEM, as well as LSM analysis. Release experiments were conducted to investigate the release behavior of the essential oils from their respective lignin and PLGA carrier materials. The study found that lignin nanoparticles were more effective at trapping and retaining essential oils than PLGA nanoparticles, despite having larger average particle diameters and a more uneven particle size distribution. An analysis of the lignin coatings showed that they formed a uniform layer that covered most of the surface pores. PLGA nanoparticles formed a film-like layer on the cell walls, and after leaching, larger areas of native wood were evident on the wood samples treated with PLGA NPs compared to the ones coated with lignin NPs. The loading capacity and efficiency varied with the type of essential oil, while the release behaviors were similar between the two essential oil types applied in this study.

The Effect of Different Factors on Poly(lactic-co-glycolic acid) Nanoparticle Properties and Drug Release Behaviors When Co-Loaded with Hydrophilic and Hydrophobic Drugs.

Poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) are versatile drug nanocarriers with a wide spectrum of applications owing to their extensive advantages, including biodegradability, non-toxic side effects, and low immunogenicity. Among the numerous nanoparticle preparation methods available for PLGA NPs (the hydrophobic polymer), one of the most extensively utilized preparations is the sonicated-emulsified solvent evaporation method, owing to its simplicity, speed, convenience, and cost-effectiveness. Nevertheless, several factors can influence the outcomes, such as the types of concentration of the surfactants and organic solvents, as well as the volume of the aqueous phase. The objective of this article is to explore the influence of these factors on the properties of PLGA NPs and their drug release behavior following encapsulation. Herein, PLGA NPs were fabricated using bovine serum albumin (BSA) as a surfactant to investigate the impact of influencing factors, including different water-soluble organic solvents such as propylene carbonate (PC), ethyl acetate (PA), and dichloromethane (DCM). Notably, the size of PLGA NPs was smaller in the EA group compared to that in the DCM group. Moreover, PLGA NPs showed excellent stability, ascribed to the presence of the BSA surfactant. Furthermore, PLGA NPs were co-loaded with varying concentrations of hydrophilic drugs (doxorubicin hydrochloride) and hydrophobic drugs (celecoxib), and exhibited pH-sensitive drug release behavior in PBS with pH 7.4 and pH 5.5.

Formulation and characterization of polymeric nanoparticle of Rivastigmine for effective management of Alzheimer’s disease

Memory loss or dementia is a progressive disorder, and one of its common forms is Alzheimer’s disease (AD), effecting mostly middle aged and older adults. In the present study, we developed Rivastigmine (RIV) nanoparticles using poly(lactic-co-glycolic acid) (RIV-loaded PLGA NPs) and polyvinyl alcohol (PVA). The prepared RIV-PLGA nanoparticles was evaluated for the management of Alzheimer's disease (AD). The nanoparticles were prepared by the slightly modified nano-precipitation technique. The developed formulations were evaluated for particle size, zeta potential (ZP), polydispersibility index (PDI) and surface morphology and drug content. The experimental result revealed that prepared RIV-loaded PLGA NPs (F1) was optimized having particle size (61.2 ± 4.6 nm), PDI (0.292), ZP (−11.2 ± 1.2). SEM study confirms the prepared nanoparticles depicted non-aggregated as well smooth surface particles without any fracture. This formulation (F1) was further assessed for in vivo studies on animal model. A pharmacological screening on an animal model of Alzheimer's disease revealed that RIV-loaded PLGA NPs formulations treat CNS disorders like Alzheimer's effectively. In addition to that, an in-vivo brain cholinesterase estimation study found that, animals treated with optimized formulation significantly (p < 0.01) reduced brain cholinesterase activity when compared to scopolamine-treated animals. According to the above results, it can be concluded that RIV-loaded PLGA NPs are ideal carriers for delivering the drug at a specific target site in the brain, thus may treat Alzheimer's disease efficiently and improve patient compliance.

Synergetic approaches of fucoidan and trabectedin complex coated PLGA nanoparticles effectively suppresses proliferation and induce apoptosis for the treatment on non-small cell lung cancer

Traditional methods of treating lung cancer have not been very effective, contributing to the disease’s high incidence and death rate. As a result, Fn/Tn-PLGA NPs, a novel directed fucoidan and trabectedin complex loaded PLGA nanoparticle, were produced to investigate the role of developing therapeutic strategies for NSCLC and A549 cell lines. Quantitative real-time polymerase chain reaction was used to examine protein expression and mRNA expression, respectively. Protein activity was knocked down using specific inhibitors and short disrupting RNA transfection. Lastly, cancer cell lines H1299 and A549 were subjected to an in vitro cytotoxicity experiment. Commercial assays were used to assess the levels of cell viability, ROS and proliferation found that Fn/Tn-PLGA NPs effectively killed lung cancer cells. To examine cell death, annexin flow cytometry was employed. In addition, a scratch-wound assay was conducted to assess the migration effects of Fn/Tn-PLGA NPs in a laboratory setting. Finally, PLGA NPs covered with a mix of fucoidan and trabectedin could be a good vehicle for targeting cancerous tissues with chemotherapeutic drugs.

Sertaconazole-PLGA nanoparticles for management of ocular keratitis

Ocular fungal infections can pose severe health conditions that may develop into vision impairment and blindness. Sertaconazole (STZ) is a widely used antifungal; however, its low aqueous solubility restricts its topical application for managing ocular keratitis. This investigation aimed to develop polymeric nanoparticles as delivery carriers to improve the ophthalmic availability of STZ for treating fungal keratitis. The impact of STZ solid dispersion incorporation within polymeric nanoparticles for in vitro drug release enhancement was also evaluated. STZ-laden PLGA NPs were formulated via nanoprecipitation technology, using a 24-full factorial layout to optimize the formulation. The formed nanoparticles were assessed for encapsulation efficiency percentage, hydrodynamic size, surface charge, and polydispersity index. The selected formula exhibited a particle size of 305.9 ± 4.36 nm, an entrapment efficiency (EE%) of 98.8 ± 0.008%, a surface charge of 22.57 ± 0.23 mV, and a low polydispersity index, indicating a uniform size distribution. Incorporating STZ in a solid dispersion form with PEG 2000 at a 1:3 w/w drug-to-carrier ratio increased the hydrodynamic size of the PLGA NPs. However, no significant variation in the entrapment efficiency percentage was recorded. The developed STZ-solid dispersion-loaded PLGA NPs have round-shaped structures. DSC and FTIR spectroscopy data indicated drug amorphization with successful loading within the PLGA matrix. Introducing the drug as a solid dispersion within PLGA NPs resulted in enhancing the rate of drug dissolution at initial time intervals, followed by a controlled drug release over 24 h. STZ-PEG2000-laden PLGA NPs enhanced permeability through rabbits’ corneas (Papp), 2.5-fold higher versus STZ-loaded PLGA NPs. The antimycotic activity of the developed formulation was tested against Candida albicans, and a 4-fold reduction in the MIC value was detected upon applying the nanoparticles’ formulation embedding STZ solid dispersion versus that containing the free drug. In conclusion, the formulation of solid dispersions of STZ loaded in PLGA nanoparticles may serve as a starting point for an efficient approach to the ocular delivery of hydrophobic medications and a viable setup for the upcoming research in animal models of fungal keratitis.

The Evaluation of Anti-Osteoclastic Activity of the Novel Calcium Hydroxide Biodegradable Nanoparticles as an Intracanal Medicament

IntroductionThe aim of this study was to evaluate the anti-osteoclastic activity of calcium hydroxide–loaded poly(lactic-co-glycolic acid) nanoparticles [Ca(OH)2-loaded PLGA NPs] in comparison to calcium hydroxide nanoparticles [Ca(OH)2 NPs]. MethodsRAW 264.7 cell lines (third–fifth passage) were cultured and incubated with soluble receptor activator of nuclear factor kappa B ligand in triplicate. Subsequently, Ca(OH)2-loaded PLGA NPs and Ca(OH)2 NPs were added for 7 days to evaluate their effects on receptor activator of nuclear factor kappa B ligand–induced osteoclast differentiation of RAW 264.7 cells by tartrate-resistant acid phosphatase activity. Additionally, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was conducted to confirm the cytotoxicity of treatments to cells. ResultsTartrate-resistant acid phosphatase staining showed a significant reduction in the osteoclast number when treated with Ca(OH)2-loaded PLGA NPs compared with Ca(OH)2 NPs (P < .01). In comparison to the control, the number of osteoclasts significantly reduced upon treatment with Ca(OH)2-loaded PLGA NPs (P < .05), but there was no significant difference in Ca(OH)2 NPs. Furthermore, osteoclast morphology in both treatment groups exhibited smaller sizes than the control group. Neither Ca(OH)2-loaded PLGA NPs nor Ca(OH)2 NPs demonstrated cytotoxic effects on RAW264.7 cells. ConclusionsBoth Ca(OH)2 NPs with and without poly(lactic-co-glycolic acid) have the ability to inhibit osteoclast differentiation. However, Ca(OH)2-loaded PLGA NPs exhibit greater potential than Ca(OH)2 NPs, making them a promising intracanal medicament for cases of root resorption.

Microfluidics produced ATRA-loaded PLGA NPs reduced tuberculosis burden in alveolar epithelial cells and enabled high delivered dose under simulated human breathing pattern in 3D printed head models

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is second only to COVID-19 as the top infectious disease killer worldwide. Multi-drug resistant TB (MDR-TB) may arise because of poor patient adherence to medications due to lengthy treatment duration and side effects. Delivering novel host directed therapies (HDT), like all trans retinoic acid (ATRA) may help to improve drug regimens and reduce the incidence of MDR-TB. Local delivery of ATRA to the site of infection leads to higher bioavailability and reduced systemic side effects. ATRA is poorly soluble in water and has a short half-life in plasma. Therefore, it requires a formulation step before it can be administered in vivo. ATRA loaded PLGA nanoparticles suitable for nebulization were manufactured and optimized using a scalable nanomanufacturing microfluidics (MF) mixing approach (MF-ATRA-PLGA NPs). MF-ATRA-PLGA NPs demonstrated a dose dependent inhibition of Mtb growth in TB-infected A549 alveolar epithelial cell model while preserving cell viability. The MF-ATRA-PLGA NPs were nebulized with the Aerogen Solo vibrating mesh nebulizer, with aerosol droplet size characterized using laser diffraction and the estimated delivered dose was determined. The volume median diameter (VMD) of the MF-ATRA-PLGA NPs was 3.00 ± 0.18 μm. The inhaled dose delivered in adult and paediatric 3D printed head models under a simulated normal adult and paediatric breathing pattern was found to be 47.05 ± 3 % and 20.15 ± 3.46 % respectively. These aerosol characteristics of MF-ATRA-PLGA NPs supports its suitability for delivery to the lungs via inhalation. The data generated on the efficacy of an inhalable, scalable and regulatory friendly ATRA-PLGA NPs formulation provides a foundation on which further pre-clinical testing can be built. Overall, the results of this project are promising for future research into ATRA loaded NPs formulations as inhaled host directed therapies for TB.

A quality-by-design strategic approach for the development of bedaquiline-pretomanid nanoparticles as inhalable dry powders for TB treatment

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (M.tb) and is the second leading cause of death from an infectious disease globally. The disease mainly affects the lungs and forms granulomatous lesions that encapsulate the bacteria, making treating TB challenging. The current treatment includes oral administration of bedaquiline (BDQ) and pretomanid (PTD); however, patients suffer from severe systemic toxicities, low lung drug concentration, and non-adherence. In this study, we developed BDQ-PTD loaded nanoparticles as inhalable dry powders for pulmonary TB treatment using a Quality-by-Design (QbD) approach. The BDQ-PTD combination showed an additive/synergistic effect for M.tb inhibition in vitro, and the optimized drug ratio (1:4) was successfully loaded into polymeric nanoparticles (PLGA NPs). The QbD approach was implemented by identifying the quality target product profile (QTPPs), critical quality attributes (CQAs), and critical process parameters (CPPs) to develop efficient design space for dry powder preparation using spray drying. The three-factorial and three-level Box-Behnken Design was used to assess the effect of process parameters (CPPs) on product quality (CQAs). The Design of Experiments (DoE) analysis showed different regression models for product quality responses and helped optimize process parameters to meet QTPPs. The optimized dry powder showed excellent yield (72 ± 2 % w/w), high drug (BDQ-PTD) loading, low moisture content (<1% w/w), and spherical morphology. Further, aerosolization performance revealed the suitability of powder for deposition in the respiratory airways of the lungs (MMAD 2.4 µm and FPF > 75 %). In conclusion, the QbD approach helped optimize process parameters and develop dry powder with a suitable quality profile for inhalation delivery in TB patients.

Hydrogel of Thyme-Oil-PLGA Nanoparticles Designed for Skin Inflammation Treatment.

Thyme oil (THO) possesses excellent antibacterial and antioxidant properties which are suitable for skin inflammatory disorders such as acne vulgaris. However, THO is insoluble in water and its components are highly volatile. Therefore, these drawbacks may be overcome by its encapsulation in biodegradable PLGA nanoparticles (THO-NPs) that had been functionalized using several strategies. Moreover, cell viability was studied in HaCat cells, confirming their safety. In order to assess therapeutic efficacy against acne, bacterial reduction capacity and antioxidant properties were assessed. Moreover, the anti-inflammatory and wound-healing abilities of THO-NPs were also confirmed. Additionally, ex vivo antioxidant assessment was carried out using pig skin, demonstrating the suitable antioxidant properties of THO-NPs. Moreover, THO and THO-NPs were dispersed in a gelling system, and stability, rheological properties, and extensibility were assessed. Finally, the biomechanical properties of THO-hydrogel and THO-NP-hydrogel were studied in human volunteers, confirming the suitable activity for the treatment of acne. As a conclusion, THO has been encapsulated into PLGA NPs, and in vitro, ex vivo, and in vivo assessments had been carried out, demonstrating excellent properties for the treatment of inflammatory skin disorders.