Polycaprolactone Nanoparticles Research Articles

Polymeric nanoparticles loaded with vincristine and carbon dots for hepatocellular carcinoma therapy and imaging

Chemotherapy for hepatoblastoma is limited by organ toxicity and poor outcomes, prompting the search for new, more effective treatments with minimal side effects. Vincristine sulfate, a potent chemotherapeutic, faces challenges due to P-glycoprotein-mediated resistance and its systemic toxicity. Nanoparticles offer a promising solution by improving pharmacokinetics, targeting tumor cells, thus reducing side effects. Moreover, the use of fluorescent nanomaterials is emerging in biomedical applications such as bioimaging, detection and therapies. This study describes a promising delivery system utilizing carbon dots encapsulated with vincristine in biodegradable polycaprolactone nanoparticles via a double emulsion technique. The fine characterization of these nanoparticles showed that they are spherical, uniformly sized with around 200 nm and exhibit excellent colloidal stability. Moreover, the release profile showed prolonged release for both vincristine and carbon dots. In vitro cell viability studies revealed enhanced cancer cell inhibition for the encapsulated drug compared to the vincristine solution. The uptake study indicated clear fluorescence for carbon dots solution and vincristine and carbon dots loaded nanoparticles upon excitation. Additionally, studies on primary mouse hepatocytes demonstrated higher fluorescence intensity in treatment groups. These results suggest that vincristine and carbon dots loaded nanoparticles are effective, target-specific carriers for liver cancer treatment. Furthermore, the carbon dots were not cytotoxic, highlighting their potential in bioimaging and cancer cell studies.

Development and Evaluation of the Acaricidal Activity of Xantan Gum-Based Hydrogel and Polymeric Nanoparticles Containing Achyrocline satureioides Extract.

The Rhipicephalus microplus tick causes enormous economic losses in livestock farming around the world. Despite several promising studies carried out with plant extracts such as Achyrocline satureioides against this ectoparasite, a major obstacle is related to pharmaceutical presentation forms. There is no study showing xantan gum-based hydrogel and polycaprolactone nanoparticles containing A. satureioides extract against R. microplus larvae. The objective of this study was to incorporate A. satureioides extract to develop a nanoformulation (AScn) and a hydrogel (ASlh) and evaluate them against R. microplus larvae with the purpose of increasing the contact time of the extract with the larvae and improve the effectiveness. The ethanolic extracts were incorporated in polycaprolactone nanoparticles and characterized via analysis of the mean hydrodinamic diameter and polidispersity index. The xanthan gum-based hydrogel formulation was prepared with crude extract of A. satureioides 40 mg/mL, 0.25% xanthan gum, and 8% poloxamer, to determine the bioadhesiveness of the formulation in bovine leather and the flow rate of the formulation in the animal. The results in larvae demonstrated that when evaluated in the form of a hydrogel (ASlh), mortality was higher, with 91.48% mortality at a concentration of 20 mg/mL presenting itself as an interesting alternative for controlling this ectoparasite.

Development of a dry powder formulation for pulmonary delivery of azithromycin-loaded nanoparticles.

The COVID-19 pandemic has raised concern regarding respiratory system diseases and oral inhalation stands out as an attractive non-invasive route of administration for pulmonary diseases such as chronic bronchitis, cystic fibrosis, COVID-19 and community-acquired pneumonia. In this context, we encapsulated azithromycin in polycaprolactone nanoparticles functionalized with phospholipids rich in dipalmitoylphosphatidylcholine and further produced a fine powder formulation by spray drying with monohydrated lactose. Nanoparticles obtained by the emulsion/solvent diffusion-evaporation technique exhibited a mean hydrodynamic diameter around 195-228nm with a narrow monomodal size distribution (PdI < 0.2). Nanoparticle dispersions were spray-dried at different inlet temperatures, atomizing air-flow, aspirator air flow, and feed rate, using lactose as a drying aid, resulting in a maximal process yield of 63% and an encapsulation efficiency of 83%. Excipients and the dry powder formulations were characterized in terms of morphology, chemical structure, thermal analyses and particle size by SEM, FTIR, DSC/TGA and laser light diffraction. The results indicated spherical particles with 90% at 4.06µm or below, an adequate size for pulmonary delivery. Aerosolization performance in a NGI confirmed good aerodynamic properties. Microbiological assays showed that the formulation preserves AZM antimicrobial effect against Staphylococcus aureus and Streptococcus pneumoniae strains, with halos above 18mm. In addition, no formulation-related cytotoxicity was observed against the human cell lines BEAS-2B (lung epithelial), HUVEC (endothelial) and HFF1 (fibroblasts). Overall, the approach described here allows the production of AZM-PCL nanoparticles incorporated into inhalable microparticles, enabling more efficient pulmonary therapy of lung infections.

Smart self-assembled polymeric-MMT/Moringa Oleifera L. particles by solvent replacement method

Obesity, stemming from metabolic syndrome and energy imbalance, is a common health concern characterized by excess energy consumption and fat buildup. Moringa Oleifera L. (MO), known for its anti-obesity properties, is extracted via Soxhlet extraction. MO is extracted using the Soxhlet extraction method. To evaluate the antioxidant properties of MO powder, several analyses were conducted, including the assessment of total phenolic content (TPC), total flavonoid content (TFC), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) activity, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity. The TPC and TFC, DPPH activity, and ABTS activity values were determined to be 386.7 mg GAE/g and 82.33 mg QE/g, 32.86 %, and 49.4 % respectively. To improve drug delivery, the freeze-dried MO powder was encapsulated within a polymeric carrier, poly(e-caprolactone) (PCL). Moreover, the incorporation of montmorillonite (MMT) into the MO-loaded PCL nanoparticles enhanced the encapsulation efficiency and drug loading of MO. Nanoprecipitation was employed as a method to produce the nanoparticles, and the effects of four key parameters were studied: the ratio of aqueous phase volume to organic volume (1.5 – 10), stirring speed (400 rpm – 1200 rpm), mass weightage of MO (1 % -5 %), and mass weightage of MMT (2 % - 5 %). Design Expert was utilized for full factorial analysis to assess the impact of these parameters on encapsulation efficiency and drug loading. The optimal formulation was achieved at the ratio of aqueous phase volume to the organic volume of 1.5, stirring speed of 400 rpm, mass weightage of MO at 1 %, and mass weightage of MMT at 5% The expected encapsulation efficiency is 91.33 % and drug loading is 6.49 %.

2-AG-loaded and bone marrow-targeted PCL nanoparticles as nanoplatforms for hematopoietic cell line mobilization

BackgroundThe use of mobilizing agents for hematopoietic stem cell (HSC) transplantation is insufficient for an increasing number of patients. We previously reported lipid made endocannabinoid (eCB) ligands act on the human bone marrow (hBM) HSC migration in vitro, lacking long term stability to be therapeutic candidate. In this study, we hypothesized if a novel 2-AG-loaded polycaprolactone (PCL)-based nanoparticle delivery system that actively targets BM via phosphatidylserine (Ps) can be generated and validated.MethodsPCL nanoparticles were prepared by using the emulsion evaporation method and characterized by Zetasizer and scanning electron microscopy (SEM). The encapsulation efficiency and release profile of 2-AG were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The presence of cannabinoid receptors (CBRs) in HSCs and monocytes was detected by flow cytometry. Cell morphology and viability were assessed using transmission electron microscopy (TEM), SEM, and the WST-1 viability assay. The migration efficacy of the 2-AG and 2-AG-loaded nanoparticle delivery system on HSCs and HPSCs (TF-1a and TF-1) and monocytes (THP-1) was evaluated using a transwell migration assay.ResultsThe 140–225 nm PCL nanoparticles exhibited an increasing polydispersity index (PDI) after the addition of Ps and 2-AG, with a surface charge ranging from − 25 to -50 mV. The nanoparticles released up to 36% of 2-AG within the first 8 h. The 2-AG-Ps-PCL did not affect cellular viability compared to control on days 5 and 10. The HSCs and monocytes expressed CB1R and CB2R and revealed increased migration to media containing 1 µM 2-AG-Ps-PCL compared to control. The migration rate of the HSCs toward monocytes incubated with 1 µM 2-AG-Ps-PCL was higher than that of the monocytes of control. The 2-AG-Ps-PCL formulation provided a real time mobilization efficacy at 1 µM dose and 8 h time window via a specific CBR agonism.ConclusionThe newly generated and validated 2-AG-loaded PCL nanoparticle delivery system can serve as a stable, long lasting, targeted mobilization agent for HSCs and as a candidate therapeutic to be included in HSC transplantation (HSCT) protocols following scale-up in vivo preclinical and subsequent clinical trials.Graphical

Hybrid scaffolds for bone tissue engineering: Integration of composites and bioactive hydrogels loaded with hDPSCs

Bone tissue regeneration remains a significant challenge in clinical settings due to the complexity of replicating the mechanical and biological properties of bone environment. This study addresses this challenge by proposing a hybrid scaffold designed to enhance both bioactivity and physical stability for bone tissue regeneration. This research is the fisrt to develop a rigid 3D structure composed of polycaprolactone (PCL) and hydroxyapatite nanoparticles (nHA) integrated with a bioink containing human dental pulp stem/stromal cells (hDPSCs), alginate, nHA and collagen (Col). The biofabricated constructs were extensively characterized through cytocompatibility tests, osteogenic differentiation assessment, and biocompatibility evaluation in a rat model. In vitro results demontrated that the hybrid scaffolds presented significantly higher cell viability after 168 h compared to the control group. Furthermore, the hybrid scaffolds showed increased osteogenic differentiation relative to other groups. In vivo evaluation indicated good biocompatibility, characterized by minimal inflammatory response and successful tissue integration. These findings highlight the scaffold's potential to support bone tissue regeneration by combining the mechanical strength of PCL and nHA with the biological activity of the alginate-nHA-Col and hDPSCs bioink. The current study provides a promising foundation for the development of biomaterials aimed at improving clinical outcomes in bone repair and regeneration, particulary for the treatment of critical-size bone defects, targeted drug administration, and three-dimensional models for bone tissue engineering.

Simvastatin-loaded gelatin-capped polycaprolactone nanoparticles for the post-operative management of breast cancer

Minimal residual disease at the tumor site after surgical ablation is a major cause for tumor recurrence and metastasis. The tropism of circulating tumor cells towards injured areas increases the risk of tumor recurrence. Recent studies have reported the inability of nanocarriers to penetrate the tumor site owing to short systemic half-life, high hydrostatic pressure, and inability to extravasate the tumor tissue. In this work, we developed simvastatin-loaded polycaprolactone - gelatin core-shell nanoparticles (SNP) for post-surgical management of breast cancer (BC). NP-loaded within the hyaluronic acid solution demonstrated shear thinning behavior (n = 0.3089). SNP demonstrated cytotoxic potential in the 2-D cell culture and 3-D tumoroids of MDA-MB-231 cell line in vitro. JC-1 and rhodamine-123 based assays demonstrated the ability of SNP to induce mitochondrial membrane damage. Further, cell cycle analysis revealed that the SNP prevented the progression of cell line from G0/G1 to S-phase. Simvastatin and SNP induced early apoptosis in the MDA-MB-231 cell line. Scratch, invasion, migration, and clonogenic assays demonstrated the ability of SNP to prevent cell invasion and clonal expansion. Immunocytochemistry revealed that both SIM and SNP reduced the expression of anti-apoptotic protein BCL-2 in metastatic cell line. Overall, the developed formulation demonstrates enormous potential for the post-surgery management of BC.

Synergistic Enhancement of Mechanical and Electrochemical Properties in Grafted Polymer/Oxide Hybrid Electrolytes.

Lithium metal batteries operated with high voltage cathodes are predestined for the realization of high energy storage systems, where solid polymer electrolytes offer a possibility to improve battery safety. Al2O3_PCL is introduced as promising hybrid electrolyte made from polycaprolactone (PCL) and Al2O3 nanoparticles that can be prepared in a one-pot synthesis as a random mixture of linear PCL and PCL-grafted Al2O3. Upon grafting, synergistic effects of mechanical stability and ionic conductivity are achieved. Due to the mechanical stability, manufacture of PCL-based membranes with a thickness of 50µm is feasible, yielding an ionic conductivity of 5·10-5S cm-1 at 60°C. The membrane exhibits an impressive performance of Li deposition in symmetric Li||Li cells, operating for 1200h at a constant and low overvoltage of 54mV and a current density of 0.2mA cm-2. NMC622|Al2O3_PCL|Li cells are cycled at rates of up to 1 C, achieving 140 cycles at >80% state of health. The straightforward synthesis and opportunity of upscaling as well as solvent-free polymerization render the Al2O3_PCL hybrid material as rather safe, potentially sustainable and affordable alternative to conventional polymer-based electrolytes.

Formulation of Polymeric Nanoparticles Loading Baricitinib as a Topical Approach in Ocular Application.

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.

Immunomodulatory activity of polycaprolactone nanoparticles with calcium phosphate salts against Leishmania infantum infection

Objective: To prepare and characterize polycaprolactone (PCL) nanoparticles loaded with sonicator fragmented (SLA) and freeze- thaw Leishmania antigens (FTLA) and to investigate the in vitro immunogenicity of antigen-encapsulated nanoparticles with calcium phosphate adjuvant. Methods: The water/oil/water binary emulsion solvent evaporation method was used to synthesize antigen-loaded PCL nanoparticles. Particles were characterized by scanning electron microscopy and zeta potential measurements. Their cytotoxicity in J774 macrophages in vitro was determined by MTT analysis. In addition, the amount of nitric oxide and the level of cytokines produced by macrophages were determined by Griess reaction and ELISA method, respectively. The protective effect of the developed formulations was evaluated by determining the infection index percentage in macrophages infected with Leishmania infantum. Results: Compared to the control group, SLA PCL and FTLA PCL nanoparticles with calcium phosphate adjuvant induced a 6- and 7-fold increase in nitric oxide, respectively. Additionally, the vaccine formulations promoted the production of IFN-γ and IL-12. SLA PCL and FTLA PCL nanoparticles combined with calcium phosphate adjuvant caused an approximately 13- and 11-fold reduction in infection index, respectively, compared to the control group. Conclusions: The encapsulation of antigens obtained by both sonication and freeze-thawing into PCL nanoparticles and the formulations with calcium phosphate adjuvant show strong in vitro immune stimulating properties. Therefore, PCL-based antigen delivery systems and calcium phosphate adjuvant are recommended as a potential vaccine candidate against leishmaniasis.

In vitro and ex vivo evaluation of chitosan gel containing metformin-loaded polymeric nanoparticles for topical treatment of melanoma

Objective The purpose of this study was to prepare and evaluate chitosan (CS) gel containing metformin hydrochloride (MET)-loaded polycaprolactone (PCL) nanoparticles (NPs) for topical treatment of melanoma. Significance Topical administration of MET-PCL NPs-CS gel improves penetration of drug, decreases side effects, and increases efficacy of treatment. Methods MET-PCL NPs were prepared by double emulsion method. Particle size, charge, encapsulation efficiency (EE), release, and morphology were evaluated. MET-PCL NPs-CS gel formulation was characterized in terms of organoleptic properties, pH, gelling time, viscosity, spreadability, release, and morphology. Cytotoxicity was performed on B16F10 cells. Ex vivo permeability was done with pig skin. Results The size, charge, and EE were found to be 180 ± 10 nm, −11.4 mV, and 93%. SEM images showed that NPs were spherical and smooth. An initial burst release followed by a slower release was observed. MET-PCL NPs-CS gel was found to be transparent. The pH was 4.9 ± 0.05. The gelation time was 1.6 ± 0.2 min. The viscosity results confirm pseudoplastic behavior of gel. The spreadability by % area was 392 ± 6.4 cm. The images showed that gelling network of CS gel was composed of suspended NPs. The viscosity was between 554 and 3503 cP. MET-PCL NPs-CS gel showed prolonged release up to 72 h. On B16F10 cells, gel showed higher cytotoxicity compared to MET solution. MET-PCL NPs-CS gel had twofold higher permeability in pig skin compared with MET-CS gel. Conclusion Topical administration of MET-PCL NPs-CS gel into the skin resulted in improved dermal penetration and this promising approach may be of value in effective treatment of melanoma and other skin cancers.

Development of alginate and alginate sulfate/polycaprolactone nanoparticles for growth factor delivery in wound healing therapy

Connective tissue growth factor (CTGF) holds great promise for enhancing the wound healing process; however, its clinical application is hindered by its low stability and the challenge of maintaining its effective concentration at the wound site. Herein, we developed novel double-emulsion alginate (Alg) and heparin-mimetic alginate sulfate (AlgSulf)/polycaprolactone (PCL) nanoparticles (NPs) for controlled CTGF delivery to promote accelerated wound healing. The NPs’ physicochemical properties, cytocompatibility, and wound healing activity were assessed on immortalized human keratinocytes (HaCaT), primary human dermal fibroblasts (HDF), and a murine cutaneous wound model. The synthesized NPs had a minimum hydrodynamic size of 200.25 nm. Treatment of HaCaT and HDF cells with Alg and AlgSulf2.0/PCL NPs did not show any toxicity when used at concentrations <50 µg/mL for up to 72 h. Moreover, the NPs’ size was not affected by elevated temperatures, acidic pH, or the presence of a protein-rich medium. The NPs have slow lysozyme-mediated degradation implying that they have an extended tissue retention time. Furthermore, we found that treatment of HaCaT and HDF cells with CTGF-loaded Alg and AlgSulf2.0/PCL NPs, respectively, induced rapid cell migration (76.12% and 79.49%, P<0.05). Finally, in vivo studies showed that CTGF-loaded Alg and AlgSulf2.0/PCL NPs result in the fastest and highest wound closure at the early and late stages of wound healing, respectively (36.49%, P<0.001 on day 1; 90.45%, P<0.05 on day 10), outperforming free CTGF. Double-emulsion NPs based on Alg or AlgSulf represent a viable strategy for delivering heparin-binding GF and other therapeutics, potentially aiding various disease treatments.

Co-Delivery of an Innovative Organoselenium Compound and Paclitaxel by pH-Responsive PCL Nanoparticles to Synergistically Overcome Multidrug Resistance in Cancer.

In this study, we designed the association of the organoselenium compound 5'-Seleno-(phenyl)-3'-(ferulic-amido)-thymidine (AFAT-Se), a promising innovative nucleoside analogue, with the antitumor drug paclitaxel, in poly(ε-caprolactone) (PCL)-based nanoparticles (NPs). The nanoprecipitation method was used, adding the lysine-based surfactant, 77KS, as a pH-responsive adjuvant. The physicochemical properties presented by the proposed NPs were consistent with expectations. The co-nanoencapsulation of the bioactive compounds maintained the antioxidant activity of the association and evidenced greater antiproliferative activity in the resistant/MDR tumor cell line NCI/ADR-RES, both in the monolayer/two-dimensional (2D) and in the spheroid/three-dimensional (3D) assays. Hemocompatibility studies indicated the safety of the nanoformulation, corroborating the ability to spare non-tumor 3T3 cells and human mononuclear cells of peripheral blood (PBMCs) from cytotoxic effects, indicating its selectivity for the cancerous cells. Furthermore, the synergistic antiproliferative effect was found for both the association of free compounds and the co-encapsulated formulation. These findings highlight the antitumor potential of combining these bioactives, and the proposed nanoformulation as a potentially safe and effective strategy to overcome multidrug resistance in cancer therapy.

A comprehensive review on alpha-lipoic acid delivery by nanoparticles.

Alpha-lipoic acid (ALA) has garnered significant attention for its potential therapeutic benefits across a wide spectrum of health conditions. Despite its remarkable antioxidant properties, ALA is hindered by challenges such as low bioavailability, short half-life, and unpleasant odor. To overcome these limitations and enhance ALA's therapeutic efficacy, various nanoparticulate drug delivery systems have been explored. This comprehensive review evaluates the application of different nanoparticulate carriers, including lipid-based nanoparticles (solid lipid nanoparticles, niosomes, liposomes, nanostructured lipid carriers (NLCs), and micelles), nanoemulsions, polymeric nanoparticles (nanocapsules, PEGylated nanoparticles, and polycaprolactone nanoparticles), films, nanofibers, and gold nanoparticles, for ALA delivery. Each nanoparticulate system offers unique advantages, such as improved stability, sustained release, enhanced bioavailability, and targeted delivery. For example, ALA-loaded SLNs demonstrated benefits for skin care products and skin rejuvenation. ALA encapsulated in niosomes showed potential for treating cerebral ischemia, a condition largely linked to stroke. ALA-loaded cationic nanoemulsions showed promise for ophthalmic applications, reducing vascular injuries, and corneal disorders. Coating liposomes with chitosan further enhanced stability and performance, promoting drug absorption through the skin. This review provides a comprehensive overview of the advancements in nanoparticulate delivery systems for ALA, highlighting their potential to overcome the limitations of ALA administration and significantly enhance its therapeutic effectiveness. These innovative approaches hold promise for the development of improved ALA-based treatments across a broad spectrum of health conditions.

Magnetic scaffold constructing by micro-injection for bone tissue engineering under static magnetic field

The utilization of static magnetic fields in conjunction with tissue engineering scaffolds has demonstrated significant potential in the restoration of bone defects. However, previous techniques used for fabricating magnetic tissue engineering scaffolds have shown certain shortcomings that require further investigation. In this study, a series of scaffolds made from a combination of polylactic acid (PLA), polycaprolactone (PCL), and iron tetraoxide (Fe3O4) nanoparticles were designed and prepared using the microinjection molding technique. The composite scaffolds, which were doped with nanoparticles and fabricated through microinjection, exhibited exceptional physicochemical properties and biocompatibility. Additionally, the PLA/PCL/Fe3O4 scaffolds were found to promote the proliferation and adhesion of bone marrow cells (BMSCs) under relatively low magnetic fields (25–30 mT). These findings suggest that PLA/PCL/Fe3O4 scaffolds hold great potential for use in bone tissue engineering applications.

A remodeled ivermectin polycaprolactone-based nanoparticles for inhalation as a promising treatment of pulmonary inflammatory diseases

In recent years, ivermectin (IVM), an antiparasitic drug of low water solubility and poor oral bioavailability, has shown a profound effect on inflammatory mediators involved in diseases, such as acute lung injury, lung fibrosis, and COVID-19. In order to maximize drug bioavailability, polymeric nanoparticles can be delivered through nebulizers for pulmonary administration. The aim of this study was to prepare IVM-loaded polycaprolactone (PCL) nanoparticles (NPs) by solvent evaporation method. Box-Benkhen design (BBD) was used to optimize entrapment efficiency (Y1), percent drug release after 6 h (Y2), particle size (Y3), and zeta potential (Y4). A study was conducted examining the effects of three independent variables: PCL-IVM ratio (A), polyvinyl alcohol (PVA) concentration (B), and sonication time (C). The optimized formula was also compared to the oral IVM dispersion for lung deposition, in-vivo behavior, and pharmacokinetic parameters. The optimized IVM-PCL-NPs formulation was spherical in shape with entrapment efficiency (% EE) of 93.99 ± 0.96 %, about 62.71 ± 0.53 % released after 6 h, particle size of 100.07 ± 0.73 nm and zeta potential of -3.30 ± 0.23 mV. Comparing the optimized formulation to IVM-dispersion, the optimized formulation demonstrated greater bioavailability with greater area under the curve AUC0–t of 710.91 ± 15.22 μg .ml−1.h for lung and 637.97 ± 15.43 μg .ml−1.h for plasma. Based on the results, the optimized NPs accumulated better in lung tissues, exhibiting a twofold longer residence time (MRT 4.78 ± 0.55 h) than the IVM-dispersion (MRT 2.64 ± 0.64 h). The optimized nanoparticle formulation also achieved higher cmax (194.90 ± 5.01 μg/ml), and lower kel (0.21 ± 0.04 h−1) in lungs. Additionally, the level of inflammatory mediators was markedly reduced. To conclude, inhalable IVM-PCL-NPs formulation was suitable for the pulmonary delivery and may be one of the most promising approaches to increase IVM bioavailability for the successful treatment of a variety of lung diseases.

Erythrocyte membrane-coated nanocarriers modified by TGN for Alzheimer's disease

Alzheimer's disease (AD) is an aging-related neurodegenerative disease, and the main pathological feature was β-amyloid protein (Aβ) deposition. Recently, bioactive materials-based drug delivery system has been widely investigated for the treatment of AD. In this study, we developed a red blood cells (RBC) membrane-coated polycaprolactone (PCL) nanoparticles (NPs) loading with a therapeutic agent for AD, curcumin (Cur). A functional peptide TGNYKALHPHN (TGN) was conjugated to the surface of membrane for blood-brain barrier (BBB) transport (TGN-RBC-NPs-Cur). TGN peptide can be recognized by receptors on the BBB and has great potential for brain transport. To confirm the targeted delivery of Cur to the brain, a cell co-culturing immortalized human cerebral microvascular endothelial cells and human brain astrocytes glioblastoma (hCMEC/D3 and U-118MG) in vitro model was established. As a result, the BBB transporting ratio of TGN-RBC-NPs-FITC was 29.64% at 12 h which was approximately eight-fold than RBC-NPs-FITC. The improvement of drug accumulation in the AD lesion was confirmed by the NPs modified with the BBB-penetrating peptide in the fluorescence imaging and quantitative analysis with UPLC-MS/MS in vivo. The neuroprotective effects were evaluated with new object recognition behavioral test, in vitro AD cell model, dendritic spine stain, GFAP and IBA1 immunofluorescence stain. The spatial learning and memory abilities of the AD model mice treated with TGN-RBC-NPs-Cur were obviously enhanced compared with the AD control mice and were also better than Cur at the same dosage. These results were consistent with the values of protection index of rat adrenal pheochromocytoma cells (PC12 cells) treated by Aβ25–35. TGN-RBC-NPs-Cur increased the dendritic segments densities and restrained activation of microglia and astrocytes of AD mice, as well as reversed cognitive function of AD mice. All of the results demonstrated TGN-RBC-NPs-Cur a promising therapeutic strategy for delaying the progression of AD by designing biomimetic nanosystems to deliver drugs into the brain.

Fabrication and evaluation of the regenerative effect of a polycaprolactone/chitosan nanofibrous scaffold containing bentonite nanoparticles in a rat model of deep second-degree burn injury.

In the present study, we evaluated the effect of a nanofibrous scaffold including polycaprolactone (PCL), chitosan (CHT), and bentonite nanoparticles (Ben-NPS) on wound healing in order to introduce a novel dressing for burn wounds. PCL, PCL/CHT, and PCL/CHT/Ben-NPS nanofibrous scaffolds were fabricated by the electrospinning technique. Their structural and physiochemical characteristics were investigated by Fourier-transform infrared spectroscopy (FTIR) analysis, scanning electron microscopy (SEM), tensile strength, water contact angle, as well as, swelling and degradation profiles test. The disc diffusion assay was carried out to investigate the antibacterial potential of the scaffolds. In addition, the cell viability and proliferation ability of human dermal fibroblasts (HDFs) on the scaffolds were assessed using MTT assay as well as SEM imaging. The wound-healing property of the nanofibrous scaffolds was evaluated by histopathological investigations during 3,7, and 14 days in a rat model of burn wounds. SEM showed that all scaffolds had three-dimensional, beadles-integrated structures. Adding Ben-NPS into the PCL/CHT polymeric composite significantly enhanced the mechanical, swelling, and antibacterial properties. HDFs had the most cell viability and proliferation values on the PCL/CHT/Ben-NPS scaffold. Histopathological evaluation in the rat model revealed that dressing animal wounds with the PCL/CHT/Ben-NPS scaffold promotes wound healing. The PCL/CHT/Ben-NPS scaffold has promising regenerative properties for accelerating skin wound healing.

A multi-technique approach for nanoherbicide tracking: uptake and translocation pathways of the metribuzin nanocarrier in weed plants

A multi-technique approach indicated that the target weed species and application mode can determine the control efficacy and uptake of PCL nanoparticles, and the distribution of the metribuzin herbicide in plants, depending on NP–plant interactions.

Chitosan-Coated Azithromycin/Ciprofloxacin-Loaded Polycaprolactone Nanoparticles: A Characterization and Potency Study.

Antimicrobial resistance is a major health hazard worldwide. Combining azithromycin (AZ) and ciprofloxacin (CIP) in one drug delivery system was proposed to boost their antibacterial activity and overcome resistance. This study aims to improve azithromycin and ciprofloxacin activity by co-encapsulating them inside chitosan-coated polymeric nanoparticles and evaluating their antibacterial activity. The double emulsion method was employed to co-encapsulate AZ/CIP inside chitosan-coated polymeric nanoparticles. The formulations were evaluated for their nanoparticle size, size distribution, and zeta potential. Differential scanning calorimetry (DSC) analysis characterized the formula's thermal sustainability. Encapsulation efficiency was measured by HPLC and spectrophotometric analysis. Morphological studies used the Transmission Electron Microscopy (TEM). The in vitro release profiles of both AZ and CIP were monitored utilizing the dialysis membrane bag method. The micro-dilution assay assessed the antimicrobial activity against a clinical isolate of Klebsiella pneumoniae. The prepared AZ/CIP-poly-caprolactone nanoparticles were spherical; their size range was 184.0 ± 3.3-190.4 ± 5.6 nm and had high size uniformity (poly-dispersity index below 0.2). The zeta potential ranged from -21.2 ± 2.4 to -27.0 ± 2.5 mV, while chitosan-coated nanoparticles showed a positive zeta potential value ranging from 8 to 11 mV. The thermal study confirmed the amorphous state of both antibiotics inside the nanoparticles. The results of the in vitro release study indicated a slow and uniform rate of release for both drugs extended over 4-days, with a faster rate in the case of AZ. The MIC values reported for both chitosan-coated NP have been tremendously reduced by at least 15 folds of pure CIP and more than 60 folds of pure AZ. The co-encapsulation of AZ/CIP into chitosan-coated polymeric nanoparticles has been successfully achieved. The produced particles showed many beneficial attributes of uniform particle sizes below 200 nm and high zeta potential values. Chitosan-coated polymeric nanoparticles extensively enhanced the antibacterial activity of both AZ/CIP against bacteria.