Emulsion Solvent Evaporation Method Research Articles

DoE Enabled Development and In-Vitro Optimization of Curcumin-tagged Cilostazol Solid Nano Dispersion

Background: Diabetes is a prevailing disease worldwide and its complications are also hazardous including nephropathy. Drug available to treat Diabetic Nephropathy (DN) faces bioavailability issues related to solubility and absorption of drugs. Cilostazol (CLT) is a BCS class II drug that is poorly water-soluble which affects its therapeutic efficacy. CLT reduces reactive oxy-gen species (ROS) increased in DN. Curcumin (Cur) is also hydrophobic but Cur has many therapeutic efficacies like anti-inflammatory and antioxidant properties that help for the treatment of DN. Objective: The objective of the current study was to develop and optimize the Cilostazol Solid Dis-persion Nanoparticle (SDN) to improve the bioavailability of the drug by tagging it with Cur by us-ing PVP VA S 630 as polymer and Poloxamer 407 as surfactant. Method: Different formulations were developed using the emulsion solvent evaporation method, PVP VA S 630 as the hydrophilic polymer, and Poloxamer 407 as a surfactant. Two-factor, three-level Box-Behnken Design (BBD) was used for statistical analysis of the selected process variable's main effect and interactive effect on the response. Curcumin tagging was also done for the entire batches. Nanoparticles were characterized by FT-IR spectroscopy, DSC, Particle size, Zeta poten-tial, Drug entrapment efficiency, Solubility, and % CDR studies. Results: Among the 17 different formulations (CLT1-CLT 17), with a solubility of 39.5 μg/ml, a % CDR of 99.55, a typical particle size of 219.67 nm with a PDI of 0.258, entrapment efficiency of 73.47%, and a -10.6 mV of Zeta potential, CLT-15 was optimized. To determine CLT and curcu-min, the simultaneous UV calibration method was created. Overall, the DSC study indicated the amorphous nature of the Nano Dispersion, which in turn means the successful entrapment of the CLT in the Nano Dispersion matrix. TEM images also confirmed the spherical nanoparticles. The optimized batch of drugs tagged with curcumin was compared with the plain drug Solid Dispersion Nanoparticles. Conclusion: Together with the molecules of curcumin, the solid nano dispersion of CLT was pro-duced, which will add to the benefits of the management of Diabetic Nephropathy. In the current study, we underline the importance of utilising both API and phytochemicals in the treatment of Di-abetic Nephropathy, and we anticipate further basic research or clinical trials to support innovative treatments. It is possible to use these matrix-forming polymers for active ingredients with poor sol-ubility, whether they are natural or synthetic. It has also been demonstrated that these carriers (PVP VA S 630 & Poloxamer) increase the dissolution rate (in-vitro).

Optimization of O/W Emulsion Solvent Evaporation Method for Itraconazole Sustained Release Microspheres.

Itraconazole, a commonly used antifungal drug in the clinic approved by U.S. Food and Drug Administration (FDA), has been gradually found to have anti-tumor, angiogenesis inhibition and other pharmacological activities. However, its poor water solubility and potential toxicity limited its clinical application. In order to improve the water solubility and reduce the side effects caused by the high concentration of itraconazole, a novel preparation method of itraconazole sustained release microspheres was established in this study. Firstly, five kinds of polylactic acid-glycolic acid (PLGA) microspheres loaded with itraconazole were prepared by oil/water (O/W) emulsion solvent evaporation and then characterized by infrared spectroscopy. Then the particle size and morphology of the microspheres were observed by scanning electron microscope (SEM) and transmission electron microscope (TEM). After that, the particle size distribution, drug loading rate, entrapment efficiency, and drug release experiments were evaluated. Our results showed the microspheres prepared in this study had uniform particle size distribution and good integrity. Further study found that the average drug loading of the five kinds of microspheres prepared with PLGA 7505, PLGA 7510, PLGA 7520, PLGA 5020 and PLGA 0020 were 16.88, 17.72, 16.72, 16.57, and 16.64%, respectively, and the encapsulation rate all reached about 100%. More surprisingly, the release experimental results showed that the microspheres prepared with PLGA 7520 did not show sudden release, showing good sustained release performance and high drug release rate. To sum up, this study optimized the preparation method of sustained-release microspheres without sudden release, which provides a new solution for the delivery of itraconazole in the clinic.

Enhanced Cytotoxic Activity of 6-Mercaptopurine-Loaded Solid Lipid Nanoparticles in Hepatic Cancer Treatment.

6-Mercaptopurine (6-MCP) is an antiproliferative purine analog used in acute lymphoblastic leukemia, non-Hodgkin lymphoma, and inflammatory bowel disease (Crohn's disease, ulcerative colitis). Although 6-MCP has the great therapeutic potential for cancer and immunosuppressant-related diseases, 6-MCP is not readily soluble in water, presents a high first-pass effect, short half-life (0.5-1.5 h), and implies a low bioavailability (16%). On the contrary, solid lipid nanoparticles (SLNs) are prepared from solid lipids at room temperature and body temperature. In this study, SLNs were prepared w/o/w double emulsion-solvent evaporation method using Precirol ATO5 as matrix lipid. In the emulsion stabilization, surfactant (Tween 80) and polymeric stabilizer (polyvinyl alcohol [PVA]) were used. Two group formulations using Tween 80 and PVA were compared in terms of particle size, polydispersity index, zeta potential encapsulation efficiency%, and process yield%. Differential calorimetric analysis and release properties were examined for optimum formulation, and release kinetics were calculated. According to studies, sustained release was obtained with SLNs by the Korsmayer-Peppas kinetic model. The in vitro cytotoxicity studies were performed on the hepatocarcinoma (HEP3G) cell line. According to the results, successful SLN formulations were produced, and PVA was found best stabilizer. Optimum formulation exhibited significantly higher cytotoxic effects on HEP3G than on pure 6-MCP. These results demonstrated that solid lipid nanodrug delivery systems have great potential for formulation of 6-MCP.

Lipase‐Responsive Rifampicin‐Based Biodegradable PCL Nanocarrier for Antibacterial Treatment

AbstractRifampicin (RFP) is a first‐line drug used to treat a variety of infections, including wound infections but has limitations in its use due to its toxicity. Hence, an urgent need exists for the development of suitable carriers for the delivery of the antibiotic. In this study, a novel approach is introduced for drug administration, employing stimulus‐responsive carriers to achieve an on‐demand strategy. This innovative method aims to minimize the dosage and frequency of drug administration, consequently lowering cytotoxicity levels. We used the lipases‐sensitive polycaprolactone (PCL) to produce nanocomposites loaded with rifampicin (PCL−RFP NPs). Nanoparticles were prepared by a single‐step emulsion solvent evaporation method. The size distribution of blank nanoparticles (PCL NPs) and PCL−RFP NPs were 172±30 nm and 229±58 nm, respectively. The liberation of RFP from PCL−RFP NPs was monitored over a period of 72 h in the absence and the presence of lipase was 9.46±0.24 % and 53.3±3.33 %, respectively, indicating responsive behavior. The minimum inhibitory concentration to lipase‐expressing Staphylococcus aureus (S. aureus) of PCL−RFP NPs was significantly improved compared to the free drug. Cytotoxicity tests using human dermal fibroblasts showed that the nanocomposites had better biocompatible when compared to the free drug. These findings indicate that the developed nanocomposite carriers have the potential to be promising candidates for delivering antibiotics in the field of biomedicine.

Effect of Surfactant on controlling the Size of Octadecylamine-based Solid Lipid Nanoparticles and Toxicity

Surfactants play a major role in solid lipid nanoparticles’ (SLNs) composition and properties, especially in terms of particle size and zeta potential. Not only the type of the surfactants but also their amounts and chemical compatibility with the lipid core within the formulation cause good changes. In this study, our goal was to determine the effect of tween 80 (a non-ionic surfactant) on octadecylamine (cationic lipid)-based SLN formulation and its influence on SLNs properties. Also, we examined the effect of sonication and filtration as mechanical forces on the particle size, zeta potential and PDI features. Five different formulations were performed by the emulsion solvent evaporation method. Particle size distribution, zeta potential and PDI values were determined by Zetasizer via the dynamic light scattering method. We obtained SLNs resulting from different formulations and one formulation was selected with the most suitable properties for further studies. The stability of the SLNs was examined by incubating them at 4 °C in the dark for particular time intervals and the results revealed not only minimal changes in particle size but also no significant changes in zeta potential and PDI values. The nanoparticles were characterized morphologically with Transmission electron microscopy (TEM) and Atomic force microscopy (AFM). The chemical characterization was performed by Fourier-transform infrared spectroscopy (FT-IR). In vitro cytotoxicity via MTT assay on L929 mouse fibroblast cell line was performed and cell viability was determined over 63% for all concentrations.

Dual receptor specific nanoparticles targeting EGFR and PD-L1 for enhanced delivery of docetaxel in cancer therapy

Dual-receptor targeted (DRT) nanoparticles which contain two distinct targeting agents may exhibit higher cell selectivity, cellular uptake, and cytotoxicity toward cancer cells than single-ligand targeted nanoparticle systems without additional functionality. The purpose of this study is to prepare DRT poly(lactic-co-glycolic acid) (PLGA) nanoparticles for targeting the delivery of docetaxel (DTX) to the EGFR and PD-L1 receptor positive cancer cells such as human glioblastoma multiform (U87-MG) and human non-small cell lung cancer (A549) cell lines. Anti-EGFR and anti-PD-L1 antibody were decorated on DTX loaded PLGA nanoparticles to prepare DRT-DTX-PLGA via. single emulsion solvent evaporation method. Physicochemical characterizations of DRT-DTX-PLGA, such as particle size, zeta-potential, morphology, and in vitro DTX release were also evaluated. The average particle size of DRT-DTX-PLGA was 124.2 ± 1.1 nm with spherical and smooth morphology. In the cellular uptake study, the DRT-DTX-PLGA endocytosed by the U87-MG and A549 cells was single ligand targeting nanoparticle. From the in vitro cell cytotoxicity, and apoptosis studies, we reported that DRT-DTX-PLGA exhibited high cytotoxicity and enhanced the apoptotic cell compared to the single ligand-targeted nanoparticle. The dual receptor mediated endocytosis of DRT-DTX-PLGA showed a high binding affinity effect that leads to high intracellular DTX concentration and exhibited high cytotoxic properties. Thus, DRT nanoparticles have the potential to improve cancer therapy by providing selectivity over single-ligand-targeted nanoparticles.

A convergent synthetic platform of hydrogels enclosing prednisolone-loaded nanoparticles for the treatment of chronic actinic dermatitis

ABSTRACT Recurrent eczematous lesions and acute itching describe chronic actinic dermatitis (CAD). Continuous use of corticosteroids might result in a dermal adverse effect. Chitosan (CS)-coated PLGA nanoparticles encapsulated prednisolone (PDS) and co-encapsulated to poloxamer hydrogel to enhance anti-inflammatory action and reduce side effects. The PDS@NPs were synthesized using the solvent-emulsification evaporation method, and their physical and chemical properties were analysed. Ex vivo drug absorption experiment was conducted utilizing the Franz diffusion cells in vitro. Toxic effects on human fibroblasts and keratinocytes were not observed in the nanoparticle formulations. Nanoparticles and hydrogels altered PDS’s release kinetics, but not by the non-encapsulated PDS (NE@PDS). Nanoparticles could not penetrate the stratum corneum of removed the skin, which shows the nano-encapsulation of PDS improved skin absorptions. Pseudoplastic and non-Newtonian behaviour was seen in all hydrogels. The nanoformulations appear to be a promising option for glucocorticoid delivery to individuals with chronic actinic dermatitis (CAD).

Doxorubicin-loaded mPEG-pPAd-mPEG triblock polymeric nanoparticles for drug delivery systems: Preparation and in vitro evaluation

Conventional methods in chemotherapy and radiotherapy do not target tumor sites treating breast cancer. Therefore, they cause some extra adverse effects on healthy tissues and cells, which bring fatal results. In recent applications, drug delivery systems have been used to target tumors directly or their environment indirectly. The new approach has attracted considerable interest due to its promise to overcome breast cancer with little adverse effect. Synthetic or natural polymer shell capsules are generally used to deliver therapeutic agents due to their biocompatibility and biodegradability. Doxorubicin (DOX), a convenient chemotherapeutic agent, was encapsulated using produced monomethyl ether ended poly(ethylene glycol)-poly(propylene adipate)- monomethyl ether ended poly(ethylene glycol) (mPEG-pPAd-mPEG) triblock copolymers in this study. The nanoparticle form of the prepared mPEG-pPAd-mPEG tri-block copolymer system was produced by a double emulsion-solvent evaporation method. To prepare triblock copolymer, firstly, poly (propylene adipate) (pPAd) was synthesized and characterized by using Fourier Transform Infrared (FT-IR) spectroscopy structurally and end-group analysis method to determine the number average molecular weight. The nanoparticle's size characteristics were measured by the Dynamic Light Scattering (DLS) method, while encapsulation efficacy and DOX-release profile were determined by spectrofluorometer instrument. Following the production of the nanoparticles, the antiproliferative effect and cellular uptake efficiency of the mPEG-pPAd-mPEG nanoparticles (PANPs), the doxorubicin-loaded mPEG-pPAd-mPEG nanoparticles (DPANPs), ICG-loaded mPEG-pPAd-mPEG nanoparticles (IPANPs), free-DOX, and free-ICG were tested on MCF-7 and MDA-MB-231 breast cancer cell line. The cytotoxicity analysis revealed that the DPANPs exhibited low toxicity compared to free-DOX. The physical and chemical analysis showed that the nanoparticles produced within this study's scope could be used as new drug delivery systems for breast cancer treatment.

DOE supported optimization of biodegradable polymeric nanoparticles based dry powder inhaler for targeted delivery of afatinib in non-small cell lung cancer

Poly (lactic-co-glycolic acid) (PLGA) based nanoparticles are increasingly being used to deliver anticancer agents directly to the lungs. This approach offers targeted delivery of the drug, which minimizes the risk of side effects associated with oral administration. Afatinib-loaded PLGA nanoparticles were fabricated with a double emulsification solvent evaporation method and optimized by a factorial design (32) approach. The optimized batch of afatinib-loaded polymeric nanoparticles exhibited suitable entrapment efficiency (78.15 ± 2.20% w/w), drug loading (3.90 ± 0.11% w/w), particle size (198.1 ± 3.5 nm), and zeta potential (−0.519 ± 0.197 mV). A dry powder-based inhaled drug delivery platform is rapid-acting, handy, and self-administered that is expected to enhance patient compliance. The lyophilization method was used to convert afatinib-loaded PLGA nanoparticles into dry powder form. The formulated afatinib-loaded PLGA nanoparticles dry powder inhaler (PLGA NDPI) demonstrated good flow properties with 77.86 ± 3.02% drug content and 6.883 ± 0.369 μm particle size distribution. With more than 85% of the dosage released from an inhaler device in the eight-stage cascade impactor through an in-vitro lung deposition investigation, the particles also proved their capacity to penetrate the deeper area of the lung. Further, the in-vitro drug release study demonstrated more than 80% drug release from PLGA NDPI at different pH of phosphate buffer solutions. A549 adenocarcinoma cell line cytotoxicity investigation revealed that PLGA NDPI has a stronger potential for suppressing tumour cell proliferation than pure drug solution. Fluorescein isothiocyanate (FITC) encapsulated afatinib PLGA NDPI formulation was more effectively absorbed intracellularly by adenocarcinoma cells than plain FITC dye. Taken together, the results suggest that, the formulated afatinib PLGA NDPI can be a promising approach for targeted lung delivery of the anticancer agent.

Encapsulation of Neem oil from Azadirachta indica into Poly (lactic-co-glycolic acid) as a novel sprayable miticide system with long-term storage stability and controlled release kinetic

In this study, Neem oil (NO) was extracted from the seeds of Azadirachta indica as a natural miticide agent. To prolong the insecticidal activity and control the sustainable release, various concentrations of NO were encapsulated in poly(D, L-lactic-co-glycolic) acid (PLGA) copolymers and high and low molecular weight (Mw) polyvinyl alcohol (PVAH and PVAL) microparticles (MPs) using the single and double emulsion solvent evaporation method. The effects of different parameters, such as the molecular weight of the stabilizing agent (PVA), stirring time, and polymer concentrations, on the size, stability, morphology, encapsulation efficiency, and release kinetics of the MPs were investigated. The presence of NO in PLGA/PVA MPs was confirmed by a shift in the glass transition temperature (Tg) to lower temperatures in the DSC thermograph, the appearance of peaks at 2854 cm−1 in the FTIR spectrum, a peak at 205 nm in the UV–vis spectrum and a rough surface in SEM. Moreover, the release kinetics of the MPs demonstrated sustained release of NO over 48 h. In terms of MPs storage, temperature affected short-term stability, while long-term stability after one year in a dark environment at room temperature was confirmed by the particles' strength. The miticide assay on dust mites Dermatophagoides pteronyssinus revealed that MPs with the highest NO concentration (PLGA/PVAL/NO 65%) exhibited the most effective miticidal activity, achieving a 100% kill rate after 24 h. Finally, the colloidal dispersion and stability of the MPs over time were assessed using rheology, and the results confirmed the particles' spray ability for miticide application.

EFFECT OF PREPARATION TEMPERATURE ON ETHYLCELLULOSE MICROSPHERE PROPERTIES PREPARED BY OIL-IN-OIL EMULSION SOLVENT EVAPORATION PROCESS

The present study aims to formulate ethylcellulose microspheres using the oil-in-oil emulsion solvent evaporation method and judge the outcome of processing temperature on their features. The effects of the evaporation rate of the solvent on the particle properties and drug release characteristics of the microspheres were studied. Here, microspheres were prepared at different processing temperatues, viz., 10 0 C, 25 0 C, and 40 0 C, and their impact on the various characteristics of microspheres like surface topography, micrometrics, yield percent, encapsulation efficiency, in vitro dissolution, Fourier-transform infrared spectroscopy (FTIR) and release kinetics were elaborately studied. The FTIR study revealed that processing temperature did not affect drug-polymer compatibility. The study observed that the processing temperature had a great influence on the various characteristics of the prepared microsphere. It was observed from sieve analysis that the mean particle size of the microsphere increased with an increase in processing temperature, and the SEM study also corroborated the same result. SEM photographs showed processing at a higher temperature resulted in particles with a smooth surface, in contrast to a lower processing temperature that forms a bumpy surface. Furthermore, a higher temperature favoured formulation with a higher entrapment efficiency (94.42 ± 0.9 %) as compared to a lower temperature (85.2 ± 0.72 %). For a noteworthy timeframe, indinavir sulfate frames a solid solution in the ethylcellulose matrix and proceeds with the amorphous state. The results of an in vitro drug dissolution study showed that microspheres formulated at a higher temperature had a more sustaining effect as compared to those formulated at a lower temperature, which may have resulted due to their higher mean particle size. Using the Korsemeyer Peppas power law, it was found that the way drugs are released is controlled by diffusion.

Facilitated encapsulation of a nonionic contrast agent for X-ray computed tomography into lipid vesicles by the multiple emulsification-solvent evaporation method

We studied the encapsulation of iohexol (Ihex), a nonionic contrast agent used for X-ray computational tomography, into lipid vesicles using the multiple emulsification-solvent evaporation method to formulate a nanosized contrast agent. This lipid vesicle preparation method consists of three steps: (1) primary emulsification for producing water-in-oil (W/O) emulsions containing fine water droplets that will be converted to the internal water phase of the lipid vesicles, (2) secondary emulsification for formulating multiple water-in-oil-in-water (W/O/W) emulsions encapsulating the fine water droplets containing Ihex, and (3) solvent evaporation to remove the oil phase solvent (n-hexane) and to form lipid bilayers surrounding the fine inner droplets, resulting in the formation of lipid vesicles encapsulating Ihex. As the diameter and Ihex concentration of the primary W/O emulsion droplets decreased, a higher Ihex encapsulation yield was obtained for the final lipid vesicles. The entrapment yield of Ihex in the final lipid vesicles varied significantly with the emulsifier (Pluronic® F-68) concentration in the external water phase of W/O/W emulsion, and the highest yield (65%) was obtained when the emulsifier concentration was 0.1 wt%. We also investigated the powderization of lipid vesicles encapsulating Ihex via lyophilization. The powderized vesicles were dispersed in water after rehydration and maintained their controlled diameters. The entrapment yield of Ihex in powderized lipid vesicles was maintained for over 1 month at 25 ˚C, while significant leakage of Ihex was observed in the lipid vesicles suspended in the aqueous phase.

A cascade-responsive nanoplatform with tumor cell-specific drug burst release for chemotherapy.

Most of the nanomedicines can reduce the side effects of anti-tumor chemical drugs but do not have good enough therapeutic efficacy, largely due to the sustained drug release profile. It might be a promising alternative strategy to develop a cascade-responsive nanoplatform against tumor with the burst release of chemotherapeutics based on the highly efficient tumor cell targeting delivery. In this work, we constructed innovative nanoparticles (PMP/WPH-NPs) consisting of two functional polymers. PMP contained the MMP-2 enzyme sensitive linker and disulfide bond, which could respond to the tumor-overexpressing enzyme MMP-2 and high-level glutathione. While WPH promoted tumor penetration and acid-responsive drug release by modifying cellular penetrating peptides and polymerizing L-histidine. PMP/WPH-NPs exhibited outstanding features including longer blood circulation time, promoted tumor-specific accumulation, enhanced tumor penetration and efficient escape from lysosomes. Subsequently, the model drug paclitaxel (PTX), widely used in the tumor chemotherapy, was encapsulated into PMP/WPH-NPs via an emulsion solvent evaporation method. Within a short period of time, PTX-PMP/WPH-NP in simulated tumor cellular microenvironment could release 8 times more PTX than that in the physiological environment, demonstrating a good potential in tumor cell-specific burst drug release. In addition, PTX-PMP/WPH-NPs exhibited stronger anti-tumor activity than PTX in vitro and in vivo, which also had good biocompatibility according to the hemolysis assay and H&E staining. In summary, our work has succeeded in designing an original polymeric nanoplatform for programmed burst drug release based on the tailored tumor targeting delivery system. This new approach would facilitate the clinical translation of more anti-tumor nanomedicines. STATEMENT OF SIGNIFICANCE: Biomaterials responsive to the tumor-specific stimulus has conventionally used in the targeted-delivery of anti-tumor drugs. However, the levels of common stimulus are not uniformly distributed and not high enough to effectively trigger drug release. In an effort to achieve a better specific drug release and promote the chemotherapeutic efficacy, we constructed a cascade responsive nanoplatform with tumor cell-specific drug burst release profile. The tailored biomaterial could overcome the bio-barriers in vivo and succeeded in the programmed burst drug release based on the tumor cell-specific delivery of chemotherapeutics.

A biopolymeric mesh enriched with PLGA microparticles loaded with AT101 for localized glioblastoma treatment

Current treatment strategies for glioblastoma (GBM) including surgical resection and adjuvant radio/chemotherapy result in a limited progression-free survival time of patients due to rapidly occurring tumor recurrences. The urgent need for more effective treatments has led to the development of different approaches for localized drug delivery systems (DDSs) offering the advantages of reduced systemic side effects. A promising candidate for the treatment of GBMs is AT101, the R-(-)-enantiomer of gossypol due to its ability to induce apoptosis or trigger autophagic cell death in tumor cells. Here, we present an alginate-based drug-releasing mesh ladened with AT101-loaded PLGA microspheres (AT101-GlioMesh). The AT101-loaded PLGA microspheres were fabricated using an oil-in-water emulsion solvent evaporation method obtaining a high encapsulation efficiency. The drug-loaded microspheres enabled the release of AT101 over several days at the tumor site. The cytotoxic effect of the AT101-loaded mesh was evaluated using two different GBM cell lines. Strikingly, encapsulation of AT101 in PLGA-microparticles and subsequent embedding in GlioMesh resulted in a sustained delivery and more efficient cytotoxic effect of AT101 on both GBM cell lines. Thus, such a DDS holds promise for GBM therapy likely by preventing the development of tumor recurrences.

Preparation, characterization, and thermal properties of microencapsulated palmitic acid with ethyl cellulose shell as phase change material impregnated wood

In this work, palmitic acid (PA) was encapsulated in ethyl cellulose (EC) by emulsification–solvent evaporation method. The morphology and particle size of the PCMs were examined using SEM and particle size analysis, and similar particle size (80 % is between 0 and 100 μm) was observed. The crystal phase and chemical structure of microencapsulated phase change materials (MPCM) were measured by XRD (X-ray diffractometer) and FTIR (Fourier transformation infrared spectroscope), observed that there is no chemical bond between EC and PA, but a physical bond. TGA (thermogravimetric analyzer) and DSC (differential scanning calorimeter) analysis were used to thermal properties including phase change temperature, enthalpy, thermal stability, the thermal conductivity of MPCM, and MPCMW. The results show that MPCM possesses excellent thermal stability at working temperature, and the most satisfying samples are MPCM2,3 with phase change enthalpy of 98.85 J/g, 135.1 J/g, and phase change temperature of 58.29 °C and 60.76 °C (medium-temperature zone (buildings fields)), respectively. Microencapsulation of PA with EC is one of the most important achievements of the study. Poplar (Populus euramericana) wood samples were impregnated with MPCM using a vacuum-pressure process (MPCMW). After impregnation, approximately 15 % weight gain was obtained in wood samples. It was determined that there was no change in the chemical structure and crystallinity ratios of the impregnated samples by FTIR and XRD, and thermal decomposition took place in two stages by TGA analysis. MPCMW samples started to decompose at 200 °C. Latent heat storage of 30.8–82.62 J/g between 59.70 and 61.73 °C was measured for MPCMW. MPCMW had great durability with latent heat of 40–50 J/g after 50 heating-cooling cycles. The thermal conductivity enhancements are about 40 % higher than the reported corresponding values for poplar wood. Using the microcapsule-impregnated wood, a new method for developing and utilizing high-value poplar wood in the energy storage is provided.

Mucoadhesive Cationic Bromelain Laden Nanocarriers Restore Patency of Airway Hyperresponsive Remodeling via Nasal Route

AbstractBromelain, a complex mixture of proteolytic cysteine proteases has shown positive attributes in management of allergen induced inflammatory conditions. However, efficient use of bromelain in clinics is restricted by bromelain instability at storage conditions and on oral use. Therefore, the goal of present investigation is to encapsulate bromelain in rationally tailored mucoadhesive polymeric nanocarriers for nasal delivery to refurbish its anti‐asthmatic activity and improve bioavailability. Bromelain laden Eudragid RL 100 nanocarriers (Br‐EuNCs) are engineered via double emulsion solvent evaporation method and optimized to amplify bromelain encapsulation within nanosize range (259.73 ± 16.51 nm). Dissolution study reveals prolonged bromelain release behavior (24 h) whereas higher mucin binding strength confirms mucoadhesive nature of Br‐EuNCs. Pharmacokinetic study in rats indicates 2.89‐fold increase in bromelain bioavailability after its encapsulation. Subsequently, pharmacodynamic studies reveal that optimized formulation significantly (p <0.05) reduces spasm, bronchial hyper‐responsiveness and inhibits convulsions in the ovalbumin induced asthma model. In addition, Br‐EuNCs significantly regulate hematological, biochemical, and immunological parameters disturbed during ovalbumin exposure. Histological studies of lung show significant protectionoffered by formulation against tissue damage during asthma. The results suggest that therapeutic performance of bromelain can be improved utilizing Br‐EuNCs as a platform via nasal route for asthma management.

RGD peptide modified RBC membrane functionalized biomimetic nanoparticles for thrombolytic therapy

In recent years, the fabrication of nano-drug delivery systems for targeted treatment of thrombus has become a research hotspot. In this study, we intend to construct a biomimetic nanomedicine for targeted thrombus treatment. The poly lactic-co-glycolic acid (PLGA) was selected as the nanocarrier material. Then, urokinase and perfluoro-n-pentane (PFP) were co-loaded into PLGA by the double emulsification solvent evaporation method to prepare phase change nanoparticles PPUNPs. Subsequently, the RGD peptide-modified red blood cell membrane (RBCM) was coated on the surface of PPUNPs to prepare a biomimetic nano-drug carrier (RGD-RBCM@PPUNPs). The as-prepared RGD-RBCM@PPUNPs possessed a “core-shell” structure, have good dispersibility, and inherited the membrane protein composition of RBCs. Under ultrasound stimulation, the loaded urokinase could be rapidly released. In vitro cell experiments showed that RGD-RBCM@PPUNPs had good hemocompatibility and cytocompatibility. Due to the coated RGD-RBC membrane, RGD-RBCM@PPUNPs could effectively inhibit the uptake of macrophages. In addition, RGD-RBCM@PPUNPs showed better thrombolytic function in vitro. Overall, the results suggested that this biomimetic nanomedicine provided a promising therapeutic strategy for the targeted therapy of thrombosis.Graphical

Abstract 835: Translational nanotechnology-based cancer vaccine to re-educate host immune response against metastatic cancers

Abstract Sixty percent of melanoma patients present brain metastases, having low response rates to current systemic therapies, which do not prolong survival. New therapeutic options to address this clinical need are urgent. Here, we report the development of a polymeric nanoparticle as a cancer nanovaccine capable of selectively co-targeting toll-like receptor function and PD-L1 expression to improve antigen presentation and subsequent effector immune cell function within brain microenvironment. Mannose-poly(lactic-co-glycolic acid)/poly(lactic acid) (man-PLGA/PLA) nanoparticles (NP) were prepared by a modified double emulsion solvent evaporation method, to deliver combinations of melanoma neoantigens, toll-like receptor ligands and regulators of the PD-1/PD-L1 axis. NP physicochemical properties were fully characterized, including size, surface charge and morphology. The amount of melanoma neoantigens and immune regulators entrapped within NP was determined by HPLC. Immature dendritic cells (DC) were used to evaluate the impact of NP on cell viability, and to assess NP uptake kinetics by flow cytometry. NP ability to target and trigger the activation of DC and T cells, was assessed in the lymph nodes and spleen of immunized mice. The NP anti-tumor immune-mediated effect was evaluated in vivo in two primary melanoma-bearing immunocompetent mouse models (B16F10 and B16MO5), and in a melanoma brain metastasis (MBM) mouse model (B16F10), which also included the immune profiling within tumor site by flow cytometry, before and after treatment.NP presented an average diameter of 180 nm, narrow polydispersity index, surface charge close to neutrality, spherical morphology, and high loadings of the neoantigens and immunoregulators. NP did not affect DC viability and were extensively internalized by immature DC. NP were preferentially taken-up in vivo by DC, increasing the expression of activation/maturation markers at DC surface, such as CD80 and CD86. NP elicited antigen-specific T-cell responses, by the significant increase in the expression of TNF-alpha and IFN-gamma (TH1-guided response). In vivo combination of NP with anti-PD-L1 induced a potent immune-mediated anti-tumor response in both primary and preclinical models of MBM, overcoming tumor development with an increased overall survival. This combination re-shaped immune and stroma cell populations in primary tumor and MBM microenvironment, which presented a marked infiltration of cytotoxic T cells that correlated with a decreased expression of PD-1 and PD-L1 within the TME. The synergy between our nanovaccine and anti-PD-L1 provide essential insights to devise alternative combinations regiments to improve the efficacy of immune checkpoint inhibitors in metastatic melanoma, thus opening new line for this unmet medical need. Citation Format: Barbara Carreira, Rita A. Acúrcio, Sabina Pozzi, Ron Kleiner, Liane I. Moura, Ana I. Matos, Daniela vaskovich, Carina Peres, Adelaide Fernandes, Sara Xapelli, Ronit Satchi-Fainaro, Helena F. Florindo. Translational nanotechnology-based cancer vaccine to re-educate host immune response against metastatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 835.

Poly-(lactic-co-glycolic acid) /poly-(vinyl alcohol) and cobalt ferrite magnetic nanoparticles as vanillin carriers

ABSTRACT Besides being known by food and perfume industries, vanillin has also important pharmacological properties such as anti-inflammatory and antibacterial activities. The use of magnetic nanoparticles as carriers for a vanillin delivery system is a way to explore its benefits in human beings. In this paper, poly(lactic-co-glycolic acid) (PLGA) nanoparticles stabilized by poly(vinyl alcohol) (PVA) and containing magnetic CoFe2O4 and vanillin have been prepared using a double emulsion-solvent evaporation method. The morphology, particle size, structure, and surface properties of the nanoparticles were investigated by transmission electron microscopy, zeta-potential measurements, X-ray diffractometry, Fourier transform infrared spectroscopy, magnetic hysteresis loops, and thermogravimetric analysis. The spherical nanoparticles presented negative charge, with zeta-potential values ranging from −9.15 to −5.64 mV, high thermal stability, superparamagnetic properties, and excellent encapsulation of the vanillin (around 80%). Accordingly, such PLGA/PVA nanoparticles encapsulating vanillin and CoFe2O4 exhibited the desired features to suggest their potential use as drug delivery systems.

Surface-Modified Inhaled Microparticle-Encapsulated Celastrol for Enhanced Efficacy in Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer affecting the pleural lining of the lungs. Celastrol (Cela), a pentacyclic triterpenoid, has demonstrated promising therapeutic potential as an antioxidant, anti-inflammatory, neuroprotective agent, and anti-cancer agent. In this study, we developed inhaled surface-modified Cela-loaded poly(lactic-co-glycolic) acid (PLGA) microparticles (Cela MPs) for the treatment of MPM using a double emulsion solvent evaporation method. The optimized Cela MPs exhibited high entrapment efficiency (72.8 ± 6.1%) and possessed a wrinkled surface with a mean geometric diameter of ~2 µm and an aerodynamic diameter of 4.5 ± 0.1 µm, suggesting them to be suitable for pulmonary delivery. A subsequent release study showed an initial burst release up to 59.9 ± 2.9%, followed by sustained release. The therapeutic efficacy of Cela MPs was evaluated against four mesothelioma cell lines, where Cela MP exhibited significant reduction in IC50 values, and blank MPs produced no toxicity to normal cells. Additionally, a 3D-spheroid study was performed where a single dose of Cela MP at 1.0 µM significantly inhibited spheroid growth. Cela MP was also able to retain the antioxidant activity of Cela only while mechanistic studies revealed triggered autophagy and an induction of apoptosis. Therefore, these studies highlight the anti-mesothelioma activity of Cela and demonstrate that Cela MPs are a promising inhalable medicine for MPM treatment.