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Recent advances in understanding Alzheimer's disease (AD) suggest the possibility of an infectious etiology, with Porphyromonas gingivalis emerging as a prime suspect in contributing to AD. P. gingivalis may invade systemic circulation via weakened oral/intestinal barriers and then cross the blood-brain barrier (BBB), reaching the brain and precipitating AD pathology. Based on the proposed links between P. gingivalis and AD, a prospective approach is the development of an oral nanovaccine containing P. gingivalis antigens for mucosal delivery. Targeting the gut-associated lymphoid tissue (GALT), the nanovaccine may elicit both mucosal and systemic immunity, thereby hampering P. gingivalis ability to breach the oral/intestinal barriers and the BBB, respectively. The present study describes the optimization, characterization, and in vitro evaluation of a candidate chitosan-coated poly(lactic-co-glycolic acid) (PLGA-CS) nanovaccine containing a P. gingivalis antigen extract. The nanocarrier was prepared using the double emulsion solvent evaporation method and optimized for selected experimental factors, e.g. PLGA amount, surfactant concentration, w1/o phase ratio, applying a d-optimal statistical design to target the desired physicochemical criteria for its intended application. After nanocarrier optimization, the nanovaccine was characterized in terms of particle size, polydispersity index (PdI), ζ-potential, encapsulation efficiency (EE), drug loading (DL), morphology, and in vitro release profile, as well as for mucoadhesivity, stability under simulated gastrointestinal conditions, antigen integrity, in vitro cytotoxicity and uptake using THP-1 macrophages. The candidate PLGA-CS nanovaccine demonstrated appropriate physicochemical, mucoadhesive, and antigen release properties for oral delivery, along with acceptable levels of EE (55.3 ± 3.5 %) and DL (1.84 ± 0.12 %). The integrity of the encapsulated antigens remained uncompromised throughout NPs production and simulated gastrointestinal exposure, as confirmed by SDS-PAGE and Western blotting analyses. Furthermore, the nanovaccine showed effective in vitro uptake, while exhibiting low cytotoxicity. Taken together, these findings underscore the potential of PLGA-CS NPs as carriers for adequate antigen mucosal delivery, paving the way for further investigations into their applicability as vaccine candidates against P. gingivalis.
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Poly(lactic-co-glycolic acid) (PLGA) hydrogels are highly utilized in biomedical research due to their biocompatibility, biodegradability, and other versatile properties. This review comprehensively explores their synthesis, properties, sustained release mechanisms, and applications in drug delivery. The introduction underscores the significance of PLGA hydrogels in addressing challenges like short half-lives and systemic toxicity in conventional drug formulations. Synthesis methods, including emulsion solvent evaporation, solvent casting, electrospinning, thermal gelation, and photopolymerization, are described in detail and their role in tailoring hydrogel properties for specific applications is highlighted. Sustained release mechanisms-such as diffusion-controlled, degradation-controlled, swelling-controlled, and combined systems-are analyzed alongside key kinetic models (zero-order, first-order, Higuchi, and Peppas models) for designing controlled drug delivery systems. Applications of PLGA hydrogels in drug delivery are discussed, highlighting their effectiveness in localized and sustained chemotherapy for cancer, as well as in the delivery of antibiotics and antimicrobials to combat infections. Challenges and future prospects in PLGA hydrogel research are discussed, with a focus on improving drug loading efficiency, improving release control mechanisms, and promoting clinical translation. In summary, PLGA hydrogels provide a promising platform for the sustained delivery of therapeutic agents and meet diverse biomedical requirements. Future advancements in materials science and biomedical engineering are anticipated to further optimize their efficacy and applicability in clinical settings. This review consolidates the current understanding and outlines future research directions for PLGA hydrogels, emphasizing their potential to revolutionize therapeutic delivery and improve patient outcomes.
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Alveolar echinococcosis (AE) is a severe disease caused by the infection with the larval stage of Echinococcus multilocularis, the metacestode. As there is no actual curative drug therapy, recommendations to manage AE patients are based on radical surgery and prophylactic administration of albendazole or mebendazole during 2 years to prevent relapses. There is an urgent need for new therapeutic strategies for the management of AE, as the drugs in use are only parasitostatic, and can induce toxicity. This study aimed at developing a drug delivery system for mefloquine, an antiparasitic compound which is highly active against E. multilocularis in vitro and in experimentally infected mice. We formulated mefloquine-loaded PLGA-PEG-COOH (poly-(lactic-co-glycolic acid)) nanoparticles that exhibit stable physical properties and mefloquine content. These nanoparticles crossed the outer acellular laminated layer of metacestodes in vitro and delivered their content to the inner germinal layer within less than 5 min. The in vitro anti-echinococcal activity of mefloquine was not altered during the formulation process. However, toxicity against hepatocytes was not reduced when compared to free mefloquine. Altogether, this study shows that mefloquine-loaded PLGA-PEG-COOH nanoparticles are promising candidates for drug delivery during AE treatment. However, strategies for direct parasite-specific targeting of these particles should be developed.
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Echinococcus multilocularis , Mefloquina , Nanopartículas , Polietilenglicoles , Animales , Mefloquina/farmacología , Mefloquina/administración & dosificación , Echinococcus multilocularis/efectos de los fármacos , Ratones , Polietilenglicoles/química , Nanopartículas/química , Equinococosis/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Femenino , Ratones Endogámicos BALB C , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Antihelmínticos/farmacología , Antihelmínticos/administración & dosificación , Antihelmínticos/química , Humanos , Poliglactina 910RESUMEN
Topical ocular drug delivery faces several challenges due to the eye's unique anatomy and physiology. Physiological barriers, tear turnover, and blinking hinder the penetration of drugs through the ocular mucosa. In this context, nanoparticles offer several advantages over traditional eye drops. Notably, they can improve drug solubility and bioavailability, allow for controlled and sustained drug release, and can be designed to specifically target ocular tissues, thus minimizing systemic exposure. This study successfully designed and optimized PLGA and PCL nanoparticles for delivering baricitinib (BTB) to the eye using a factorial design, specifically a three-factor at five-levels central rotatable composite 23+ star design. The nanoparticles were small in size so that they would not cause discomfort when applied to the eye. They exhibited low polydispersity, had a negative surface charge, and showed high entrapment efficiency in most of the optimized formulations. The Challenge Test assessed the microbiological safety of the nanoparticle formulations. An ex vivo permeation study through porcine cornea demonstrated that the nanoparticles enhanced the permeability coefficient of the drug more than 15-fold compared to a plain solution, resulting in drug retention in the tissue and providing a depot effect. Finally, the in vitro ocular tolerance studies showed no signs of irritancy, which was further confirmed by HET-CAM testing.
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Hot melt extrusion (HME) processed Poly (lactic-co-glycolic acid) (PLGA) implant is one of the commercialized drug delivery products, which has solid, well-designed shape and rigid structures that afford efficient locoregional drug delivery on the spot of interest for months. In general, there are a variety of material, processing, and physiological factors that impact the degradation rates of PLGA-based implants and concurrent drug release kinetics. The objective of this study was to investigate the impacts of PLGA's material characteristics on PLGA degradation and subsequent drug release behavior from the implants. Three model drugs (Dexamethasone, Carbamazepine, and Metformin hydrochloride) with different water solubility and property were formulated with different grades of PLGAs possessing distinct co-polymer ratios, molecular weights, end groups, and levels of residual monomer (high/ViatelTM and low/ ViatelTM Ultrapure). Physicochemical characterizations revealed that the plasticity of PLGA was inversely proportional to its molecular weight; moreover, the residual monomer could impose a plasticizing effect on PLGA, which increased its thermal plasticity and enhanced its thermal processability. Although the morphology and microstructure of the implants were affected by many factors, such as processing parameters, polymer and drug particle size and distribution, polymer properties and polymer-drug interactions, implants prepared with ViatelTM PLGA showed a smoother surface and a stronger PLGA-drug intimacy than the implants with ViatelTM Ultrapure PLGA, due to the higher plasticity of the ViatelTM PLGA. Subsequently, the implants with ViatelTM PLGA exhibited less burst release than implants with ViatelTM Ultrapure PLGA, however, their onset and progress of the lag and substantial release phases were shorter and faster than the ViatelTM Ultrapure PLGA-based implants, owing to the residual monomer accelerated the water diffusion and autocatalyzed PLGA hydrolysis. Even though the drug release profiles were also influenced by other factors, such as composition, drug properties and polymer-drug interaction, all three cases revealed that the residual monomer accelerated the swelling and degradation of PLGA and impaired the implant's integrity, which could negatively affect the subsequent drug release behavior and performance of the implants. These results provided insights to formulators on rational PLGA implant design and polymer selection.
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Carbamazepina , Preparaciones de Acción Retardada , Dexametasona , Liberación de Fármacos , Tecnología de Extrusión de Fusión en Caliente , Metformina , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Solubilidad , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Dexametasona/química , Dexametasona/administración & dosificación , Metformina/química , Metformina/administración & dosificación , Preparaciones de Acción Retardada/química , Carbamazepina/química , Carbamazepina/administración & dosificación , Tecnología de Extrusión de Fusión en Caliente/métodos , Implantes de Medicamentos/química , Ácido Poliglicólico/química , Portadores de Fármacos/química , Calor , Ácido Láctico/químicaRESUMEN
Ectodermal mesenchymal stem cells-derived conditioned medium (EMSCs-CM) has been reported to protect against ulcerative colitis (UC) in mice, but its underlying mechanism in alleviating UC need to be further elucidated. Here, it is reported that EMSCs-CM could attenuate pro-inflammatory response of LPS-induced IEC-6 cells and regulate the polarization of macrophages towards anti-inflammatory type in vitro. Furthermore, PLGA microspheres prepared by the double emulsion method were constructed for oral delivery of EMSCs-CM (EMSCs-CM-PLGA), which are beneficial for colon-targeted adhesion of EMSCs-CM to the damaged colon mucosa. The results showed that orally-administered of EMSCs-CM-PLGA microspheres reduced inflammatory cells infiltration and maintained the intestinal mucosal barrier. Further investigation found that EMSCs-CM-PLGA microspheres treatment gradually inhibited the activation of NF-κB pathway to regulate M1/M2 polarization balance in colon tissue macrophages, thereby alleviating DSS-induced UC. These results of this study will provide a theoretical basis for clinical application of EMSCs-CM in UC repair.
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Colitis Ulcerosa , Macrófagos , Células Madre Mesenquimatosas , Microesferas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Animales , Colitis Ulcerosa/terapia , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/inmunología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Medios de Cultivo Condicionados/farmacología , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Ratones , Colon/patología , Colon/efectos de los fármacos , FN-kappa B/metabolismo , Sulfato de Dextran , Masculino , Línea Celular , Mucosa Intestinal/patología , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Modelos Animales de Enfermedad , Ratas , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Ratones Endogámicos C57BL , HumanosRESUMEN
Pediatric forearm fractures, particularly involving the shaft or diaphysis, are common injuries typically resulting from accidental trauma during various activities. Traditional treatment involves closed reduction and casting; however, surgical intervention may be necessary in certain cases. The gold standard surgical approach utilizes elastic stable intramedullary nailing (ESIN), but a newer technique uses bioabsorbable intramedullary nails made of poly(lactic-co-glycolic acid) (PLGA). This study aims to compare the outcomes of these two surgical methods in pediatric diaphyseal forearm fractures. We retrospectively reviewed 86 patients who underwent operative treatment due to the diaphyseal fractures of the forearm in the Surgical Division, Department of Pediatrics, Medical School, University of Pécs, Pécs, Hungary between 2018 and September 2022. The mean age was 9.48 (ranging from 4 to 17). A total of 41 patients underwent surgery with PLGA implants (RESIN technique), while 45 patients were treated with titanium elastic nails (ESIN technique). Various factors including patient demographics, injury mechanisms, fracture characteristics, and complications were assessed. Both groups showed similar gender distribution, with a majority of fractures occurring in boys (the male-female ratio was 31:10 in the PLGA group, while in the titanium elastic nailing (TEN) group, this ratio was 29:16, with no statistical difference between the groups (p > 0.005). The average age of the patients treated with PLGA implants (8.439 years) was lower compared to those treated with titanium nails (10.422 years). A statistically significant difference was found regarding the average age of the two groups (p = 0.0085). Left-sided injuries were more prevalent in both groups (59% of the cases in the PLGA group and 69% in the TEN group, with no statistically significant difference, p = 0.716), and fractures typically involved both the radius and ulna. This represents 93% of the cases in the PLGA group and 80% in the TEN group. Regarding the involvement of bones, we also did not find a statistically significant difference (p = 0.123). The mechanisms of injury predominantly involved indirect force, such as falls (30 cases in the PLGA group and 27 cases in the TEN group), and no statistically significant difference was found (p = 0.139) regarding the mechanism of the injury. Complication rates were lower in the PLGA group (7%) compared to the titanium group (20%). The treatment of pediatric diaphyseal forearm fractures using PLGA implants appears to be a viable alternative to traditional titanium implants. Advantages include no need for secondary surgery and associated cost savings and reduced complication rate and stress associated with anesthesia and surgery. Prospective randomized trials are warranted to further validate these findings and explore long-term outcomes.
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End groups of poly(Lactide-co-glycolide) (PLGA) play an important role in determining the properties of polymers for use in drug delivery systems. For instance, it has been reported that the encapsulation efficiency in PLGA microspheres varies significantly between ester-terminated and acid-terminated PLGA. More importantly, the in-vivo degradation time of such polymer excipients is influenced by the functional end-group of the copolymer used. The end group distribution in PLGA polymers has been studied using electrospray and matrix-assisted laser-desorption/ionization - high-resolution mass spectrometry. In both cases, the application of these methods is typically limited to PLGA having a molecular weight of up to 4 kDa. 13Carbon-nuclear-magnetic-resonance has also been reported as a method to differentiate and quantify PLGA end groups with a molecular weight up to 136 kDa. However, reported NMR methods take over 12 h per sample, limiting throughput.Cryoprobe NMR can reduce the time required for the process, however such NMR equipment is costly, which makes it unsuitable for the quality control of PLGA. Here, we present a normal-phase liquid chromatography method capable of resolving functionality type distribution (FTD) and, partially, chemical composition distribution (CCD) in commercial PLGA polymers obtained from ring opening polymerization. This method can separate PLGA polymers with a molecular weight of up to 183.0 kDa while also enabling the simultaneous separation of the difference of Lactic acid (LA)/Glycolic acid (GA) ratios. To achieve this, a cross-linked diol column was used with a ternary gradient from HEX to 0.1 % v/v TEA in EA to 0.1 % v/v FA in THF to allow first for the elution of mono-ester terminated PLGA, followed by the di-acid terminated. In addition, a separation of ester-terminated PLGA in the difference of the LA/GA ratio was achieved. This method is expected to aid in understanding the correlation between PLGA's FTD, CCD, and physical properties, facilitating product development and quality control.
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Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Peso Molecular , Ácido Láctico/química , Cromatografía Liquida/métodos , Espectroscopía de Resonancia Magnética , Concentración de Iones de HidrógenoRESUMEN
Biodegradable polymers, encompassing both natural and synthetic polymers, have demonstrated efficacy as carriers for synthetic drugs, natural bioactive molecules, and inorganic metals. This is due to their ability to control the release of these substances. As a result, various advanced materials, such as nanoparticle-loaded hydrogels, nanofibrous scaffolds, and nanocomposites, have been developed. These materials have shown promise in enhancing processes, such as cell proliferation, vascular angiogenesis, hair growth, and wound healing management. Natural polymers, including hyaluronic acid, collagen, chitosan, gelatin, and alginate, as well as synthetic polymers like polylactic acid, polyglycolic acid, polylactic co-glycolic acid, and PCA, have significant potential for promoting wound healing. This study examines the advancements in biodegradable polymers for wound healing, specifically focusing on each polymer and its distinctive formulations. It also discusses the in-vitro experiments conducted using different cell lines, as well as the in-vivo studies that explore the numerous uses of these polymers in wound healing. The discussion also included the exploration of modifications or combinations of several polymers, as well as surface changes, in order to produce synergistic effects and address the limitations of individual polymers. The goal was to expedite the healing process of different chronic wounds. Due to this, there have been notable advancements in the technological use of polymeric mixes, including biodegradable polymer-based scaffolds, which have accelerated the process of wound healing.
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Alzheimer's disease remains an unsolved neurological puzzle with no cure. Current therapies offer only symptomatic relief, hindered by limited uptake through the blood-brain barrier. Auranofin, an FDA-approved compound, exhibits potent antioxidative and anti-inflammatory properties targeting brain disorders. Yet, its oral bioavailability challenge prompts the exploration of nanoformulation-based solutions enhancing blood-brain barrier penetrability. The study aimed to investigate the neuroprotective potential of auranofin nanoparticles in streptozotocin-induced AD rats. Auranofin-containing polylactic-co-glycolic acid nanoparticles were formulated by the multiple emulsion solvent evaporation method. Characterization was done by determining entrapment efficiency, particle size distribution, surface charge, and morphology. An in vivo study was performed by administering streptozotocin (3 mg/kg/i.c.v., days 1 and 3), auranofin (5 and 10 mg/kg), auranofin nanoparticles (2.5 and 5 mg/kg), and donepezil (2 mg/kg) for 14 days orally. Behavioral deficits were evaluated using the open field test, Morris water maze, objective recognition test, change in oxidative stress levels, and AD markers in the brain. Following the decapitation of the rats, the brains were excised to isolate the hippocampus. Subsequent analyses included the quantification of biochemical and neuroinflammatory markers, as well as the assessment of neurotransmitter levels. The characterization of auranofin nanoparticles showed an entrapment efficiency of 98%, an average particle size of 101.5 ± 10.3 nm, a surface charge of 27.5 ± 5.10 mV, and a polydispersity index of 0.438 ± 0.12. In vivo, administration of auranofin and auranofin nanoparticles significantly reversed streptozotocin-induced cognitive deficits, biochemical alteration, neuroinflammatory markers, and neurotransmitter levels. The present finding suggests that auranofin nanoparticles have more significant neuroprotective potential than auranofin alone. The therapeutic efficacy may be attributed to its antioxidant and anti-inflammatory properties, as well as its positive neuromodulatory effects. Therefore, our findings suggest that it could be a promising candidate for Alzheimer's disease therapy.
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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 110.8 nm, polydispersity index value of 0.042, and Zeta potential of -13.26 mV. The encapsulation efficiency and drug loading of NPs are 82.57% and 11.80%, respectively, and the cumulative release after 35 days 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.
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INTRODUCTION: Localized delivery of angiogenesis-promoting factors such as small molecules, nucleic acids, peptides, and proteins to promote the repair and regeneration of damaged tissues remains a challenge in vascular tissue engineering. Current delivery methods such as direct administration of therapeutics can fail to maintain the necessary sustained release profile and often rely on supraphysiologic doses to achieve the desired therapeutic effect. By implementing a microparticle delivery system, localized delivery can be coupled with sustained and controlled release to mitigate the risks involved with the high dosages currently required from direct therapeutic administration. METHODS: For this purpose, poly(lactic-co-glycolic acid) (PLGA) microparticles were fabricated via anti-solvent microencapsulation and the loading, release, and delivery of model angiogenic molecules, specifically a small molecule, nucleic acid, and protein, were assessed in vitro using microvascular fragments (MVFs). RESULTS: The microencapsulation approach utilized enabled rapid spherical particle formation and encapsulation of model drugs of different sizes, all in one method. The addition of a fibrin scaffold, required for the culture of the MVFs, reduced the initial burst of model drugs observed in release profiles from PLGA alone. Lastly, in vitro studies using MVFs demonstrated that higher concentrations of microparticles led to greater co-localization of the model therapeutic (miRNA) with MVFs, which is vital for targeted delivery methods. It was also found that the biodistribution of miRNA using the delivered microparticle system was enhanced compared to direct administration. CONCLUSION: Overall, PLGA microparticles, formulated and loaded with model therapeutic compounds in one step, resulted in improved biodistribution in a model of the vasculature leading to a future in translational revascularization.
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Targeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous tissue. These strategies can be affected by transmetalation of the parent radionuclide by competing ions in vivo and the bond-breaking recoil energy of decay daughters. The retention of α-emitting radionuclides and the dose delivered to cancer cells are influenced by these processes. Encapsulating α-emitting radionuclides within nanoparticles can help overcome many of these challenges. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are a biodegradable and biocompatible delivery platform that has been used for drug delivery. In this study, PLGA nanoparticles are utilized for encapsulation and retention of actinium-225 ([225Ac]Ac3+). Encapsulation of [225Ac]Ac3+ within PLGA nanoparticles (Zave = 155.3 nm) was achieved by adapting a double-emulsion solvent evaporation method. The encapsulation efficiency was affected by both the solvent conditions and the chelation of [225Ac]Ac3+. Chelation of [225Ac]Ac3+ to a lipophilic 2,9-bis-lactam-1,10-phenanthroline ligand ([225Ac]AcBLPhen) significantly decreased its release (< 2%) and that of its decay daughters (< 50%) from PLGA nanoparticles. PLGA nanoparticles encapsulating [225Ac]AcBLPhen significantly increased the delivery of [225Ac]Ac3+ to murine (E0771) and human (MCF-7 and MDA-MB-231) breast cancer cells with a concomitant increase in cell death over free [225Ac]Ac3+ in solution. These results demonstrate that PLGA nanoparticles have potential as radionuclide delivery platforms for TAT to advance precision radiotherapy for cancer. In addition, this technology offers an alternative use for ligands with poor aqueous solubility, low stability, or low affinity, allowing them to be repurposed for TAT by encapsulation within PLGA nanoparticles.
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Actinio , Nanopartículas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Nanopartículas/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Actinio/química , Humanos , Línea Celular Tumoral , Animales , Partículas alfa/uso terapéutico , Ratones , Femenino , Materiales Biocompatibles/química , Neoplasias de la Mama/tratamiento farmacológico , Radioinmunoterapia/métodosRESUMEN
BACKGROUND: Diclofenac sodium (DS) and celecoxib (CEL) are primary anti-inflammatory agents used in the treatment of osteoarthritis (OA). Formulating these drugs into extended-release versions can effectively address the issue of multiple daily doses. In this study, we designed and synthesized a novel poly(lactic-co-glycolic acid) (PLGA) nanoliposome as a dual-drug delivery sustained-release formulation (PPLs-DS-CEL) to achieve long-lasting synergistic treatment of OA with both DS and CEL. METHODS: PPLs-DS-CEL was synthesized by the reverse evaporation method and evaluated for its physicochemical properties, encapsulation efficiency, drug release kinetics and biological properties. A rat OA model was established to assess the therapeutic efficacy and biosafety of PPLs-DS-CEL. RESULTS: The particle size of PPLs-DS-CEL was 218.36 ± 6.27 nm, with a potential of 32.56 ± 3.28 mv, indicating a homogeneous vesicle size. The encapsulation of DS and CEL by PPLs-DS-CEL was 95.18 ± 4.43% and 93.63 ± 5.11%, with drug loading of 9.56 ± 0.32% and 9.68 ± 0.34%, respectively. PPLs-DS-CEL exhibited low cytotoxicity and hemolysis, and was able to achieve long-lasting synergistic analgesic and anti-inflammatory therapeutic effects in OA through slow release of DS and CEL, demonstrating good biosafety properties. CONCLUSION: This study developed a novel sustained-release nanoliposomes formulation capable of co-loading two drugs for the long-acting synergistic treatment of OA. It offers a new and effective therapeutic strategy for OA treatment in the clinic settings and presents a promising approach for drug delivery systems.
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Antiinflamatorios no Esteroideos , Celecoxib , Preparaciones de Acción Retardada , Diclofenaco , Liposomas , Osteoartritis , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Celecoxib/administración & dosificación , Celecoxib/química , Celecoxib/farmacología , Animales , Liposomas/química , Diclofenaco/administración & dosificación , Diclofenaco/farmacología , Diclofenaco/química , Osteoartritis/tratamiento farmacológico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Ratas , Masculino , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Preparaciones de Acción Retardada/química , Liberación de Fármacos , Ratas Sprague-Dawley , Sinergismo Farmacológico , Tamaño de la Partícula , Humanos , Nanopartículas/químicaRESUMEN
Nanotechnology is one of the newest directions for plant-based therapies. Chronic venous disease often predisposes to long-term and invasive treatment. This research focused on the inclusion of vegetal extracts from Sophorae flos (SE), Calendulae flos (CE), and Ginkgo bilobae folium (GE) in formulations with PHB and PLGA polymers and their physicochemical characterization as a preliminary stage for possible use in the development of a complex therapeutic product. The samples were prepared by an oil-water emulsification and solvent evaporation technique, resulting in suspensions with high spreadability and a pH of 5.5. ATR-FTIR analysis revealed bands for stretching vibrations (O-H, C=O, and C-H in symmetric and asymmetric methyl and methylene) in the same regions as the base components, but switched to high or low wavenumbers and absorbance, highlighting the formation of adducts/complexes between the extracts and polymers. The obtained formulations were in the amorphous phase, as confirmed by XRD analysis. AFM analysis emphasized the morphological peculiarities of the extract-polymer nanoformulations. It could be noticed that, in the case of SE-based formulations, the dominant characteristics for SE-PHB and SE-PLGA composition were the formation of random large (SE-PHB) and smaller uniform (SE-PLGA) particles; further on, these particles tended to aggregate in the case of SE-PHB-PLGA. For the CE- and GE-based formulations, the dominant surface morphology was their porosity, generally with small pores, but larger cavities were observed in some cases (CE- and GE-PHB). The highest roughness values at the (8 µm × 8 µm) scale were found for the following samples and succession: CE-PHB < SE-PLGA < SE-PHB-PLGA. In addition, by thermogravimetric analysis, impregnation in the matrix of compression stockings was evaluated, which varied in the following order: CE-polymer > SE-polymer > GE-polymer. In conclusion, nine vegetal extract-polymer nanoformulations were prepared and preliminarily characterized (by advanced physicochemical methods) as a starting point for further optimization, stability studies, and possible use in complex pharmaceutical products.
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Insulin is the cornerstone of treatment in type 1 diabetes mellitus. However, because of its protein structure, insulin has to be administered via injection, and many attempts have been made to create oral formulations, especially using nanoparticles (NPs). The aim of this study was to compare the hypoglycemic effect of insulin-loaded NPs to that of subcutaneous insulin in an in vivo rat model of diabetes. We used biodegradable D-α-tocopherol polyethylene glycol succinate-emulsified, chitosan-capped poly(lactic-co-glycolic acid) NPs loaded with soluble human insulin in a dose of 20 IU/kg body weight, and examined the physical characteristics of NPs in vivo and in vitro. Serum glucose levels were reduced after 6 h, but the difference was not significant compared to subcutaneous insulin; at 12 h and 24 h, insulin levels were significantly higher in rats treated with NPs than in rats treated with subcutaneous insulin. There was no significant difference in serum insulin levels at 12 h and 24 h compared to non-diabetic rats. Our findings suggest that chitosan-based NPs are able to maintain good glycemic control for up to 24 h and can be considered a potential carrier for oral insulin delivery.
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Diabetes Mellitus Experimental , Hiperglucemia , Insulina , Nanopartículas , Estreptozocina , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/sangre , Insulina/sangre , Insulina/administración & dosificación , Ratas , Administración Oral , Masculino , Hiperglucemia/tratamiento farmacológico , Quitosano/química , Glucemia , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Modelos Animales de Enfermedad , Ratas Sprague-DawleyRESUMEN
Hepatocellular carcinoma (HCC) exhibits high mortality rates in the advanced stage (>90 %). Sorafenib (SORA) is a targeted therapy approved for the treatment of advanced HCC; however, the reported response rate to such a therapeutic is suboptimal (<3%). Piperine (PIP) is an alkaloid demonstrated to exert a direct tumoricidal activity in HCC and improve the pharmacokinetic profiles of anticancer drugs including SORA. In this study, we developed a strategy to improve efficacy outcomes in HCC using PIP as an add-on treatment to support the first-line therapy SORA using biodegradable Poly (D, L-Lactide-co-glycolide, PLGA) nanoparticles (NPs). SORA and PIP (both exhibit low aqueous solubility) were co-loaded into PLGA NPs (PNPs) and stabilized with various concentrations of polyvinyl alcohol (PVA). The SORA and PIP-loaded PNPs (SP-PNPs) were characterized using Fourier Transform Infrared (FTIR) Spectroscopy, X-ray Powder Diffraction (XRD), Dynamic Light Scattering (DLS), and Scanning Electron Microscopy (SEM), Release of these drugs from SP-PNPs was investigated in vitro at both physiological and acidic pH, and kinetic models were employed to assess the mechanism of drug release. The in vitro efficacy of SP-PNPs against HCC cells (HepG2) was also evaluated. FTIR and XRD analyses revealed that the drugs encapsulated in PNPs were in an amorphous state, with no observed chemical interactions among the drugs or excipients. Assessment of drug release in vitro at pH 5 and 7.4 showed that SORA and PIP loaded in PNPs with 0.5 % PVA were released in a sustained manner, unlike pure drugs, which exhibited relatively fast release. SP-PNPs with 0.5 % PVA were spherical, had an average size of 224 nm, and had a high encapsulation efficiency (SORA â¼ 82 %, PIP â¼ 79 %), as well as superior cytotoxicity compared to SORA monotherapy in vitro. These results suggest that combining PIP with SORA using PNPs may be an effective strategy for the treatment of HCC and may set the stage for a comprehensive in vivo study to evaluate the efficacy and safety of this novel formulation using a murine HCC model.
RESUMEN
The emergence of antibiotic resistance makes the treatment of bacterial infections difficult and necessitates the development of alternative strategies. Targeted drug delivery systems are attracting great interest in overcoming the limitations of traditional antibiotics. Here, we aimed for targeted delivery of rifaximin (RFX) by decorating RFX-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) with synthetic P6.2 peptide, which was used as a targeting agent for the first time. Our results showed that encapsulation of RFX into NPs increased its antibacterial activity by improving its solubility and providing controlled release, while P6.2 modification allowed targeting of NPs to S. aureus bacterial cells. A promising therapeutic approach for bacterial infections, these P6.2-conjugated RFX-loaded PLGA NPs (TR-NP) demonstrated potent antibacterial activity against both strains of S. aureus. The antibacterial activity of RFX-loaded PLGA NPs (R-NP) showed significant results with an increase of 8 and 16-fold compared to free RFX against S. aureus and MRSA, respectively. Moreover, the activity of targeted nanoparticles was found to be increased 32 or 16-fold with an MBC value of 0.0078 µg/mL. All nanoparticles were found to be biocompatible at doses where they showed antimicrobial activity. Finally, it revealed that P6.2-conjugated targeted nanoparticles extremely accumulated in S. aureus rather than E. coli.
Asunto(s)
Antibacterianos , Nanopartículas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Rifaximina , Infecciones Estafilocócicas , Staphylococcus aureus , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Rifaximina/farmacología , Rifaximina/química , Nanopartículas/química , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Infecciones Estafilocócicas/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Humanos , Rifamicinas/farmacología , Rifamicinas/química , Rifamicinas/administración & dosificación , Animales , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos/químicaRESUMEN
In addressing the challenge of enhancing orthopedic implants, 3D porous calcium phosphate (CaP) coatings on titanium (Ti) substrates modified with poly(lactic-co-glycolic acid) (PLGA) were proposed. CaP coatings on Ti were deposited using the ultrasonic-assisted micro-arc oxidation (UMAO) method, followed by modification with PLGA through a dip coating process at concentrations of 5%, 8%, and 10%. The addition of PLGA significantly improved adhesive-cohesive strength according to the scratch test, while PLGA to CaP adhesion was found to be not less than 8.1 ± 2.2 MPa according to the peel test. Tensile testing showed a typical fracture of CaP coatings and mechanisms of brittle fracture. Corrosion resistance, assessed via gravimetric and electrochemical methods in 0.9% NaCl and PBS solutions, revealed PLGA's substantial reduction in corrosion rates, with the corrosion current decreasing by two orders of magnitude even for the 5% PLGA/CaP/Ti sample. Also, the PLGA layer significantly enhanced the impedance modulus by two orders of magnitude, indicating a robust barrier against corrosion at all PLGA concentrations. Higher PLGA concentrations offered even greater corrosion resistance and improved mechanical properties. This research underscores the potential of using CaP- and PLGA-modified coatings to extend the life and functionality of orthopedic implants, addressing a significant challenge in biomedical engineering.
RESUMEN
INTRODUCTION: The 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]. METHODS: RAW 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. RESULTS: Tartrate-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. CONCLUSIONS: Both 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.