Nanoprecipitation Method Research Articles

Precise control of microfluidic flow conditions is critical for harnessing the in vitro transfection capability of pDNA-loaded lipid-Eudragit nanoparticles.

Microfluidics is widely regarded as a leading technology for industrial-scale manufacture of multicomponent, gene-based nanomedicines in a reproducible manner. Yet, very few investigations detail the impact of flow conditions on the biological performance of the product, particularly biocompatibility and therapeutic efficiency. Herein, this study investigated the engineering of a novel lipid-Eudragit hybrid nanoparticle in a bifurcating microfluidics micromixer for plasmid DNA (pDNA) delivery. Nanoparticles of ~150 nm in size, with uniform polydispersity index (PDI = 0.2) and ξ-potential of 5-11 mV were formed across flow rate ratios (FRR, aqueous to organic phase) of 3:1 and 5:1, respectively. The hybrid nanoparticles maintained colloidal stability and structural integrity of loaded pDNA following recovery by ultracentrifugation. Importantly, in vitro testing in human embryonic kidney cell line (HEK293T) revealed significant differences in biocompatibility and transfection efficiency (TE). Lipid-Eudragit nanoparticles produced at FRR 3:1 displayed high cellular toxicity (0-30% viability), compared with nanoparticles prepared at FRR 5:1 (50-100% viability). Red fluorescent protein (RFP) expression was sustained for 24-72 h following exposure of cells to nanoparticles, indicating controlled release of pDNA and trafficking to the nucleus. Nanoparticles produced at FRR 5:1 resulted in markedly higher TE (12%) compared with those prepared at FRR 3:1 (2%). Notably, nanoparticles produced using the bench-scale nanoprecipitation method resulted in lower biocompatibility (30-90%) but higher RFP expression (25-38%). These findings emphasize the need for in-depth analysis of the effect of formulation and flow conditions on the physicochemical and biological performance of gene nanomedicines when transitioning from bench to clinic.

Mechanistic Analysis of Temperature-Dependent Curcumin Release from Poly(lactic-co-glycolic acid)/Poly(lactic acid) Polymer Nanoparticles.

In this study, we investigated the mechanism of curcumin (CUR) release from poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid) (PLA) nanoparticles (NPs) by evaluating the temperature-dependent CUR release. NPs were prepared by the nanoprecipitation method using various PLGA/PLA polymers with different lactic:glycolic ratios (L:G ratios) and molecular weights. Increasing the polymer molecular weight resulted in a decrease in the particle size of NPs. The wet glass transition temperature (Tg) of PLGA/PLA NPs was lower than the intrinsic polymer Tg, which can be derived from the water absorption and nanosizing of the polymer. The reduction in Tg was more significant for the PLGA/PLA NPs with lower polymer L:G ratios and lower polymer molecular weight. The greater decrease of Tg in the lower polymer L:G ratios was possibly caused by the higher water absorption due to the more hydrophilic nature of the glycolic acid segment than that of the lactic acid segment. The efficient water absorption in PLGA/PLA NPs with lower molecular weight could cause a significant reduction of Tg as it has lower hydrophobicity. CUR release tests from the PLGA/PLA NPs exhibited enhanced CUR release with increasing temperatures, irrespective of polymer species. By fitting the CUR release profiles into mathematical models, the CUR release process was well described by an initial burst release followed by a diffusion-controlled release. The wet Tg and particle size of the PLGA/PLA NPs affected the amount and temperature dependence of the initial burst release of CUR. Above the wet Tg of NPs, the initial burst release of CUR increased sharply. Smaller particle sizes of PLGA/PLA NPs led to a higher fraction of initial CUR burst release, which was more pronounced above the wet Tg of NPs. The wet Tg and particle sizes of the PLGA/PLA NPs also influenced the diffusion-controlled CUR release. The diffusion rate of CUR in the NPs increased as the wet Tg values of the NPs decreased. The diffusion path length of CUR was affected by the particle size, with larger particle size resulting in a prolonged diffusion-controlled release of CUR. This study highlighted that for the formulation development of PLGA/PLA NPs, suitable PLGA/PLA polymers should be selected considering the physicochemical properties of PLGA/PLA NPs and their correlation with the release behavior of encapsulated drugs at the application temperature.

Novel ligand decoratedtheranostic zein nanoparticles coloaded with paclitaxel and carbon quantum dots: formulation and optimization.

Aim: The present researchfocused on development and optimization of liganddecorated theranostic nanocarrier encapsulating paclitaxel and carbon quantum dots (CQDs). Methods: CQDs were prepared by microwave-assisted pyrolysisand were characterized for particle size and fluorescence behavior. Ligand decorated zein nanoparticles, coloaded with paclitaxel and CQDs, were formulated using a one-step nanoprecipitation method and optimized for various process parameters. Results: Particle size for coated and uncoated nanoparticles was 90.16±1.65 and 179.26±3.61nm, respectively, and entrapment efficiency was >80%. The circular dichroism spectroscopy showed zein retained its secondary structure and release study showed biphasic release behavior. Conclusion: The prepared theranostic nanocarrier showed optimal fluorescence and desired release behavior without altering the secondary structure of zein.

Step-By-Step Standardization of the Bottom-Up Semi-Automated Nanocrystallization of Pharmaceuticals: A Quality By Design and Design of Experiments Joint Approach.

Nanosized drug crystals have been reported with enhanced apparent solubility, bioavailability, and therapeutic efficacy compared to microcrystal materials, which are not suitable for parenteral administration. However, nanocrystal design and development by bottom-up approaches are challenging, especially considering the non-standardized process parameters in the injection step. This work aims to present a systematic step-by-step approach throughQuality-by-Design (QbD) and Design of Experiments (DoE) for synthesizing drug nanocrystals by a semi-automated nanoprecipitation method. Curcumin is used as a drug model due to its well-known poor water solubility (0.6µgmL-1, 25°C). Formal and informal risk assessment tools allow identifying the critical factors. A fractional factorial 24-1 screening design evaluates their impact on the average size and polydispersity of nanocrystals. The optimization of significant factors is done by a Central Composite Design. This response surface methodology supports the rational design of the nanocrystals, identifying and exploring the design space. The proposed joint approach leads to a reproducible, robust, and stable nanocrystalline preparation of 316nm with a PdI of 0.217 in compliance with the quality profile. An orthogonal approach for particle size and polydispersity characterization allows discarding the formation of aggregates. Overall, the synergy between advanced data analysis and semi-automated standardized nanocrystallization of drugs is highlighted.

Dual Modification of Cassava Starch Using Physical Treatments for Production of Pickering Stabilizers.

Cassava starch nanoparticles (SNP) were produced using the nanoprecipitation method after modification of starch granules using ultrasound (US) or heat-moisture treatment (HMT). To produce SNP, cassava starches were gelatinized (95 °C/30 min) and precipitated after cooling, using absolute ethanol. SNPs were isolated using centrifugation and lyophilized. The nanoparticles produced from native starch and starches modified using US or HMT, named NSNP, USNP and HSNP, respectively, were characterized in terms of their main physical or functional properties. The SNP showed cluster plate formats, which were smooth for particles produced from native starch (NSNP) and rough for particles from starch modified with US (USNP) or HMT (HSNP), with smaller size ranges presented by HSNP (~63-674 nm) than by USNP (~123-1300 nm) or NSNP (~25-1450 nm). SNP had low surface charge values and a V-type crystalline structure. FTIR and thermal analyses confirmed the reduction of crystallinity. The SNP produced after physical pretreatments (US, HMT) showed an improvement in lipophilicity, with their oil absorption capacity in decreasing order being HSNP > USNP > NSNP, which was confirmed by the significant increase in contact angles from ~68.4° (NSNP) to ~76° (USNP; HSNP). A concentration of SNP higher than 4% may be required to produce stability with 20% oil content. The emulsions produced with HSNP showed stability during the storage (7 days at 20 °C), whereas the emulsions prepared with NSNP exhibited phase separation after preparation. The results suggested that dual physical modifications could be used for the production of starch nanoparticles as stabilizers for Pickering emulsions with stable characteristics.

Formulation of Budesonide-Loaded Polymeric Nanoparticles into Hydrogels for Local Therapy of Atopic Dermatitis.

Budesonide is a mineral corticoid applied in the local therapy of pediatric atopic dermatitis. Unfortunately, its dermal administration is hindered by the concomitant adverse effects and its physicochemical properties. The characteristic pH change in the atopic lesions can be utilized for the preparation of a pH-sensitive nanocarrier. In this view, the formulation of Eudragit L 100 nanoparticles as a budesonide delivery platform could provide more efficient release to the desired site, improve its penetration, and subsequently lower the undesired effects. In this study, budesonide-loaded Eudragit L100 nanoparticles were prepared via the nanoprecipitation method (mean diameter 57 nm, -31.2 mV, and approx. 90% encapsulation efficiency). Their safety was proven by cytotoxicity assays on the HaCaT keratinocyte cell line. Further, the drug-loaded nanoparticles were incorporated into two types of hydrogels based on methylcellulose or Pluronic F127. The formulated hydrogels were characterized with respect to their pH, occlusion, rheology, penetration, spreadability, and drug release. In conclusion, the developed hydrogels containing budesonide-loaded nanoparticles showed promising potential for the pediatric treatment of atopic dermatitis.

Nanoemulsions and nanocapsules loaded with Melaleuca alternifolia essential oil for sepsis treatment.

Sepsis represents a complex clinical syndrome that results from a harmful host response to infection. The infections most associated with sepsis are pneumonia, intra-abdominal infection, and urinary tract infection. Tea tree oil (TTO) has shown high antibacterial activity; however, it exhibits low aqueous solubility and high volatility, which have motivated its nanoencapsulation. In this study, the performance of nanoemulsions (NE) and nanocapsules (NC) loaded with TTO was compared. These systems were prepared by spontaneous emulsification and nanoprecipitation methods, respectively. Poly-ε-caprolactone or Eudragit® RS100 were tested as polymers for NCs whereas Tween® 80 or Pluronic® F68 as surfactants in NE preparation. Pluronic® F68 and Eudragit® RS100 resulted in more homogeneous and stable nanoparticles. In accelerated stability studies at 4 and 25 °C, both colloidal suspensions (NC and NE) were kinetically stable. NCs showed to be more stable to photodegradation and less cytotoxic than NEs. After sepsis induction by the cecal ligation and puncture (CLP) model, both NE and NC reduced neutrophil infiltration into peritoneal lavage (PL) and kidneys. Moreover, the systems increased group thiols in the kidney and lung tissue and reduced bacterial growth in PL. Taken together, both systems showed to be effective against injury induced by sepsis; however, NCs should be prioritized due to advantages in terms of cytotoxicity and physicochemical stability.

Facile fabrication of TPGS-PCL polymeric nanoparticles for paclitaxel delivery to breast cancer: investigation of antiproliferation and apoptosis induction

Breast cancer is one of the most devastating cancers that have no cure. Many therapeutic and diagnostic strategies have been extensively studied in the past decade. Cancer nanotechnology has developed as a promising approach in preclinical examinations, allowing for the early exposure of primary tumors and metastases and the efficient destruction of cancer cells. The current study aims to fabricate and analyze polymeric nanoparticles for breast cancer therapy established on a copolymeric block of α-tocopheryl polyethylene glycol 1000-b-polycaprolactone (TPGS-b-PCL) incorporating paclitaxel (PTX) (termed as T-b-P@PTX). Characterization of the physical, chemical, and structural properties and the in vitro biological activity of TPGS-b-PCL (T-b-P@PTX) obtained by the nanoprecipitation method. The in vitro cytotoxicity of the nanoparticles was explored by MTT assay using MCF-7 breast cancer cells in a time-dependent manner. The IC50 values T-b-P@PTX for MCF-7 cells 543.7 ± 2.58, 130.2 ± 3.54, 66.99 ± 3.43 in 24, 48, 72-h. Biochemical experiments showed that T-b-P@PTX has a strong ability to induce cell death and to be internalized in the MCF-7 cells. Ethidium bromide (EB)-acridine orange (AO) and nuclear DAPI staining methods investigated the morphological changes of the cells. Considering all the advantages, Paclitaxel-loaded T-b-P@PTX polymeric nanoparticle is a promising approach for treating breast cancer.

Dual-modal imaging-guided agent based on NIR-II aggregation-induced emission luminogens with balanced phototheranostic performance.

Phototherapy has garnered considerable interest for its potential to revolutionize conventional cancer treatment. Organic materials with near-infrared II (NIR-II, 1000-1700 nm) fluorescence and photothermal effects are key for precise tumor diagnosis and treatment, yet optimizing their output for higher resolution and reduced photodamage remains a challenge. Herein, a multifunctional NIR-II photosensitizer (LSC) has been developed using the aggregation-induced emission (AIE) technology. The utilization of thieno[3,2-b]thiophene as an electron-rich and bulky donor/acceptor bridge has allowed for the elongation of conjugation length and distortion of the AIE main chain. This strategic modification effectively enhances the electron push-pull effect, endowing the LSC with a Stokes shift of over 400 nm and AIE characteristics. We have successfully built-up stable nanoparticles called FA-LSC NPs using a nano-precipitation method. These nanoparticles exhibit high NIR-II fluorescent brightness (ε × QY = 1064 M-1 cm-1) and photothermal conversion efficiency (41%). Furthermore, the biocompatible FA-LSC NPs demonstrate effective tumor accumulation and exceptional photothermal therapeutic efficacy both in vitro and in vivo. These nanoparticles were applied to fluorescence-photothermal dual-mode imaging-guided photothermal ablation in a HeLa tumor xenograft mouse model, resulting in favorable photothermal clearance outcomes.

NANOPARTÍCULAS DE ZEÍNA/PVA INCORPORADAS COM EUGENOL E ÓLEO ESSENCIAL DO CRAVO-DA-ÍNDIA: OTIMIZAÇÃO DA SÍNTESE E VALIDAÇÃO ANALÍTICA PARA QUANTIFICAÇÃO DO EUGENOL

ZEIN/PVA NANOPARTICLES LOADED WITH EUGENOL AND CLOVE ESSENTIAL OIL: OPTIMIZATION OF SYNTHESIS AND ANALYTICAL VALIDATION FOR EUGENOL QUANTIFICATION. Nanoparticles of zein (NPZ) stabilized with surfactant polyvinyl alcohol (PVA), and nanoparticles of zein/PVA loaded with eugenol (NPZ-Eug) and the essential oil extracted from the clove (Syzygium aromaticum) (NPZ-OC) were produced by nanoprecipitation method. The extraction method of essential oil of the clove was carried out by the hydrodistillation technique, obtaining a content of 81.5% (m/m) of eugenol. The nanoparticle preparation method was optimized using a one-factor-at-a-time design of experiments, where different levels of variables (zein concentration, PVA concentration, and eugenol concentration) were explored. The best condition of synthesis was obtained with 0.3% (m/v) zein, 0.6% (m/v) PVA and 1.5 mg L-1 eugenol or essential oil of the clove, reaching NPs with acceptable propriety for stable nanoparticulate systems: size particles (NPZ = 113, NPZ-Eug = 229 and NPZ-OC = 279 nm), polydispersity index (PDI < 0.26), and zeta potential (≈ −30 mV). Loaded NPs showed encapsulation efficiency and drug-loading of 52 and 20% (NPZ-Eug), and 62, 27% (NPZ-OC), respectively. The quantification method of eugenol was validated by analytical parameters. Finally, all NPs produced exhibited good colloidal stability, confirming the effectiveness of PVA as a stabilizing agent, which had not been previously reported for these systems. The results obtained provide promising prospects for further investigations into its potential application as a bioinsecticide agent.

Dual-purposing disulfiram for enhanced chemotherapy and afterglow imaging using chlorin e6 and semiconducting polymer combined strategy.

Rationale: One of the main challenges in chemotherapy is achieving high treatment efficacy while minimizing adverse events. Fully exploiting the therapeutic potential of an old drug and monitoring its effects in vivo is highly valuable, but often difficult to achieve. Methods: In this study, by encapsulating disulfiram (DSF) approved by US Food and Drug Administration, semiconducting polymer nanocomplex (MEHPPV), and Chlorin e6 into a polymeric matrix F127 via nanoprecipitation method, a nanosystem (FCMC) was developed for afterglow imaging guided cancer treatment. The characteristics, stability as well as the ability of singlet oxygen (1O2) production of FCMC were first carefully examined. Then, we studied the mechanism for enhanced anti-cancer efficiency and afterglow luminescence in vitro. For experiments in vivo, 4T1 subcutaneous xenograft tumor mice were injected with FCMC via the tail vein every three days and the antitumor effect of FCMC was evaluated by monitoring tumor volume and body weight every three day. Results: The nanosystem, which combines DSF with Ce6, can generates abundant 1O2 that enhances the antitumor activity of DSF. The in vivo results show that FCMC-treated group exhibits an obviously higher tumor-growth inhibition rate of 67.89% after 15 days of treatment, compared to the control group of F127@MEHPPV-CuET. Moreover, Ce6 also greatly enhances the afterglow luminescence intensity of MEHPPV and promotes the redshift of the afterglow emission towards the ideal near-infrared imaging window, thereby enabling efficient afterglow tumor imaging in vivo. Conclusions: This multifunctional nanoplatform not only improves the anticancer efficacy of DSF, but also enables monitoring tumor via robust afterglow imaging, thus exhibiting great potential for cancer therapy and early therapeutic outcome prediction.

Neuroprotective Cognitive Effects of Nose-to-brain Delivered Linagliptin Loaded Polymeric Nanosuspension in Animal Model

Objective: Insulin resistance is a common link between diabetes mellitus (DM) and dementia. The current work emphasizes the effect of linagliptin on dementia with its neuroprotective effects, which occur directly at the neuronal level, as GLP-1 receptors are exclusively expressed in neurons. Methods: The objective of the study was to formulate linagliptin-loaded polymeric nanosuspension (LS) by nanoprecipitation method and further study their pharmaceutical, pharmacodynamics, scintigraphic, and neuroprotective effects following nose-to-brain delivery in the rat model of dementia. Results: Developed LS were spherical with z-average (250.7 nm), charge (-16.3 mV), % entrapment efficiency (95.8 ± 1.45%), and % drug loading (35.78 ± 0.19%). In vitro dissolution rate (88.56 ± 1.24%) and ex vivo permeation (81.59 ± 1.06%) of LS showed a better-sustained release profile than pure linagliptin. The spatial learning/memory in the treated group of Sprague-Dawley rats were significantly improved compared with those in the control group. Conclusion: Histopathological study of LS produced no toxicity or structural damage to the nasal mucosa. Optimum pharmaceutical characterization results improved pharmacodynamic studies/ histopathological data, and gamma-scintigraphic images proved that polymeric nanosuspensions stand out as wellappreciated approaches to deliver linagliptin more efficiently to the brain via intranasal route, thereby enhancing the neuroprotective efficacy in dementia.

High-throughput large scale microfluidic assembly of iron oxide nanoflowers@PS-b-PAA polymeric micelles as multimodal nanoplatforms for photothermia and magnetic imaging.

Magnetic nanoparticles have been extensively explored as theranostic agents both in academic and clinical settings. Their self-assembly into nanohybrids using block copolymers can lead to new nanostructures with high functionalities and performances. Herein, we demonstrate a high-throughput and scalable method to elaborate magnetic micelles by the assembly of iron oxide magnetite nanoflowers, an efficient nanoheater, and the block copolymer Poly(styrene)-block-poly(acrylic acid) via a microfluidic-assisted nanoprecipitation method. We show that the size and shape of the magnetomicelles can be easily tuned by modulating the residence time in the microfluidic channel. In addition to their biocompatibility, we demonstrate the potential of these magnetic nanohybrids as multimodal theranostic platforms capable of generating heat by photothermia and functioning as negative contrast agents in magnetic resonance imaging and as imaging tracers in magnetic particle imaging. Notably, they outperform currently commercially available particles in terms of imaging functionalities.

D-A-D organic fluorescent probes for NIR-II fluorescence imaging and efficient photothermal therapy of breast cancer.

Near-infrared second region (NIR-II) fluorescent probes are used in the diagnosis of early cancer due to their high tissue penetration. However, there are still few reports on organic small molecule fluorescent probes with NIR-II fluorescence imaging (NIR-II FI) combined with efficient photothermal therapy (PTT). In this study, planar cyclopentadithiophene (CPDT) was incorporated into the twisted structural skeleton (D-A-D), and the strong acceptor TTQ molecule (A) and the donor triphenylamine (D) were introduced to synthesize an organic small molecule (TCT) with enhanced NIR-II fluorescence emission performance. To improve the hydrophilicity of TCT molecules, we used the nanoprecipitation method to coat DSPE-mPEG2000 on the TCT molecules and obtained nanoparticles (TCT-NPs) with a strong absorption band, good water dispersibility, and NIR-II FI ability, which realized NIR-II FI-guided PTT for breast cancer tumors. Due to their effective near-infrared absorption, TCT-NPs exhibit high photothermal conversion efficiency (η = 40.1%) under 660 nm laser irradiation, making them a photothermal therapeutic agent with good performance. Therefore, TCT-NPs have the potential to diagnose, eliminate, and monitor the diffusion of cancer.

Development of Polymeric Nanoparticles of Sunitinib malate in Eudragit S 100 for anti-colon cancer targeted drug delivery

Sunitinib malate (SM) is a multi-targeted tyrosine kinase (TK) inhibitor. It is proposed as a potent anticancer drug intended for colon cancer. The current work aimed at developing Sunitinib malate -loaded nanoparticles for colon- targeting. SM loaded ES100-nanoparticles were developed by nano-precipitation method using poly vinyl alcohol (PVA) as stabilizer. Different formulation of ESNP (F1-F3) were prepared and evaluated for particle size, poly-dispersity index, and drug entrapment, using Fourier transform infrared spectroscopy (FTIR), x-ray diffraction (XRD), and scanning electron microscopy (SEM). The optimized formulation was further studied by in-vitro drug release and anticancer cell line study. The mean particle size, PDI, %EE of optimized SM loaded ESNPF2 was found to be 384.8±5.53 nm, 0.58, and 60.31% respectively. In vitro release of the optimized ESNPF2 showed 10.2 % drug release till 2 h, at 4h 29.6% and 12 h and 24 h 66.45%, 82.2% respectively at pH 7.4. SEM images and surface morphology confirmed that nanoparticles were spherical and had smooth surfaces. An MTT assay was conducted in the colon cancer cell lines (CACO2) to evaluate anti-cancerous activity of SM. SM loaded ESNPF2 showed a high potential against colon cancer cells. The overall results suggest that SM loaded ES100-nanoparticels could be a potential option for colon targeting.

Competitive inhibition of nicotine acetylcholine receptors using microneedles of nicotine and varenicline for smoking withdrawal therapy

Current strategies for smoking withdrawal conditions involve monotherapy of nicotine and combinational therapy of nicotine with varenicline or bupropion as per the CDC and FDA. The available dosage forms for nicotine are patches, gums, inhalers and nasal sprays, bupropion and varenicline are available in tablet form. This research work focused on developing a microneedle delivery system to deliver combination drug for overcoming the obstacles encountered by oral route of administration of varenicline such as severe side effects (mood swings, agitation, depressed behaviour, seizures, etc), and nicotine therapy challenges such as short half-life, repeated dosing, nausea, and vomiting. The nanoparticles of nicotine prepared by nanoprecipitation method showed particle size PTZ (356.6 ± 65.98), percentage entrapment efficiency (35.55 % ± 0.007), in-vitro drug release (47.89 % ± 0.7) for 72 h. Microneedles showed height (600 μm), width (350 μm), and tip diameter (10 μm). The nanoparticles encapsulated in microneedles showed in-vitro sustained delivery of nicotine (67.00 % ± 4.92) and varenicline (79.78 % ± 1.09) in 48 h. Nicotine released in a sustained manner attaches to the nicotine acetylcholine receptors (nAchR) to release dopamine for controlling the withdrawal challenges such as anxiety, irritability, cravings, disturbed sleep pattern, etc. The varenicline released from microneedles binds to the nAchR and inhibits dopamine release responsible for the euphoric effect induced by nicotine, and thus assists in curbing the nicotine withdrawal symptoms. This combination microneedle system offers prolonged treatment in a single application for smoking withdrawal conditions wherein patients are not in stage of oral dosing because of repeated dosing resulting in adverse effects like seizures, hypertension, sleep disturbances, insomnia, and nausea.

Natural ursolic acid based self-therapeutic polymer as nanocarrier to deliver natural resveratrol for natural therapy of acute kidney injury

Acute kidney injury (AKI) is a common kidney disease associated with excessive reactive oxygen species (ROS). Unfortunately, due to the low kidney targeting and undesired side effects, the existing antioxidant and anti-inflammatory drugs are unavailable for AKI management in clinic. Therefore, it’s essential to develop effective nanodrugs with high renal targeting and biocompatibility for AKI treatment. Herein, we reported a novel nanodrug for AKI treatment, utilizing poly(ursolic acid) (PUA) as a bioactive nanocarrier and resveratrol (RES) as a model drug. The PUA polymer was synthesized form ursolic acid with intrinsic antioxidant and anti-inflammatory activities, and successfully encapsulated RES through a nanoprecipitation method. Subsequently, we systemically investigated the therapeutic potential of RES-loaded PUA nanoparticles (PUA NPs@RES) against AKI. In vitro results demonstrated that PUA NPs@RES effectively scavenged ROS and provided substantial protection against H2O2-induced cellular damage. In vivo studies revealed that PUA NPs significantly improved drug accumulation in the kidneys and exhibited favorable biocompatibility. Furthermore, PUA NPs alone exhibited additional anti-inflammatory and antioxidant effect, synergistically enhancing therapeutic efficacy in AKI mouse models when combined with RES. Overall, our study successfully developed an effective nanodrug using self-therapeutic nanocarriers, presenting a promising option for the treatment of AKI.Graphical abstract

Revolutionizing Drug Delivery: Nicardipine Nanosuspension Formulation and In-Vitro Evaluation

Nicardipine hydrochloride, is a potent calcium channel blocker, is commonly used in the management of hypertension and angina. It is a BCS class II drug which has low aqueous solubility and high permeability. In the present study, an attempt was made to formulate and evaluate nanosuspension of Nicardipine hydrochloride using different stabilizers, namely Tween 80, PVP K30, Poloxamer 188 by using Nanoprecipitation method with the objective to improve solubility and enhance dissolution of Nicardipine hydrochloride. Prepared nanosuspensions were evaluated for drug-excipient compatibility, particle size, PDI (Polydispersity Index), Zeta potential, Drug content, Saturation solubility, In-vitro release study, Scanning electron microscopy (SEM). FTIR (Fourier Transform Infrared Spectroscopy) studies revealed the compatibility of the drug with excipients. Nanosuspension (F3), which had the lowest particle size and the highest % Drug Release, was selected as the optimum formulation. It showed the droplet size, PDI, ZP,% Drug content and %Drug release of 150.4 nm,0.243, -30.6 mV,95.52%,91.24%. Kinetic release profiles of the NS F3 revealed that it followed First order kinetics. This study showed the ability of nanosuspension system in improving the solubility and drug release of Nicardipine.
 Keywords: Nicardipine, Nanosuspension, Solubility, % Drug Release, % Drug content, Scanning electron microscopy.

Innovative Nanosuspension Formulation for Prochlorperazine and In-vitro Evaluation

Prochlorperazine is a dopamine antagonist and is used to control nausea and vomiting. It is a BCS class II drug which has low aqueous solubility and high permeability. The present study is aimed to formulate and evaluate prochlorperazine nanosuspension to improve solubility and enhance dissolution of Prochlorperazine with varying concentrations of stabilizers such as Tween 80, PVP K30, Poloxamer 188 by using nanoprecipitation method. The developed formulations were characterized for particle size and polydispersity index, total drug content, SEM, Zeta Potential and FTIR. The invitro drug release studies and invitro drug release kinetics were performed for all formulations. FTIR studies revealed that drug is compatible with the excipients. The particle size and poly dispersity index of optimized formulation was found to be 162nm and the zeta potential was found to be -30.2 mV and concluded that the system had sufficient stability. The invitro drug release was found within their acceptable ranges. The rate of dissolution of best batch was enhanced to 93.24 in 120min. Stability studies proved that nanosuspensions were more stable with no significant changes in particle size distribution. Thus the formulated nanosuspension of prochlorperazine offers a superior conventional dosage forms for drug release
 Keywords: Prochlorperazine, Nanosuspension, Solubility, Dissolution

Sodium alginate polymer nanoformulation as promising carrier for berberine delivery: Synthesis, morphology and in-vitro evaluation

The present study focused on the fabrication of berberine sodium alginate nanoparticles with a combination approach of conventional nanoprecipitation method with ionic complexation to improve its poor water solubility. The optimization of nanoformulation was done by Central Composite Design and was evaluated for DLS, entrapment efficiency, morphology, FTIR, DSC, antioxidant, anti-inflammatory, antibacterial efficacy and drug release kinetics. The particle size of optimized nanoformulation was in the range of 20 nm to 100 nm with an entrapment efficiency of 94.47%. Antibacterial efficacy of optimized nanoformulation was checked by measuring the zone of inhibition for both gram-positive bacteria and gram-negative bacteria. The optimized nanoformulation showed enhanced antimicrobial activity compared with berberine and control nanoformulation against all bacterial strains. Also, a sustained release of berberine over about 48 h was achieved with nanoformulation and the drug release followed zero-order kinetics. Thus, berberine sodium alginate nanoparticles can potentially increase the oral bioavailability of berberine and can be utilized for controlled delivery thereby reducing the side effects.