Lipid-polymer Hybrid Nanoparticles Research Articles

Poly Lactic Co-glycolic Acid d-α-tocopheryl Polyethylene Glycol 1000 Succinate Fabricated Polyethylene Glycol Hybrid Nanoparticles of Imatinib Mesylate for the Treatment of Glioblastoma Multiforme.

This study aimed to develop Imatinib Mesylate (IMT)-loaded Poly Lactic-co-Glycolic Acid (PLGA)-D-α-tocopheryl polyethylene glycol succinate (TPGS)- Polyethylene glycol (PEG) hybrid nanoparticles (CSLHNPs) with optimized physicochemical properties for targeted delivery to glioblastoma multiforme. Glioblastoma multiforme (GBM) is the most destructive type of brain tumor with several complications. Currently, most treatments for drug delivery for this disease face challenges due to the poor blood-brain barrier (BBB) and lack of site-specific delivery. Imatinib Mesylate (IMT) is one of the most effective drugs for GBM, but its primary issue is low bioavailability. Therefore, nanotechnology presents a promising solution for targeted IMT delivery to GBM. This article primarily explores the fabrication of IMT-loaded core-shell lipid-polymer hybrid nanoparticles (CSLHNPs) to achieve enhanced brain delivery with therapeutic efficacy. The primary objective of this study is to develop optimized, stable IMT-loaded hybrid nanoparticles with an encapsulated polymer matrix and to evaluate these nanoparticles using sophisticated instruments such as SEM and TEM to achieve smooth, spherical nanoparticles in a monodispersed phase. The enhanced stable formulation yielded a notable increase in entrapment efficiency, reaching 58.89 ± 0.5%. The physical stability analysis of nanoparticles was assessed over 30 days under conditions of 25 ± 2°C and 60 ± 5% relative humidity. Hemolytic assays affirmed the biocompatibility and safety profile of the nanoparticles. in vitro drug release kinetics revealed a sustained IMT release over 48 hours. The formulated CSLHNPs achieved a narrow size distribution with a mean vesicle diameter of 155.03 ± 2.41 nm and a low polydispersity index (PDI) of 0.23 ± 0.4, indicating monodispersity. A high negative zeta potential of -23.89 ± 3.47 mV ensured excellent colloidal stability in physiological conditions. XRD analysis confirmed the successful encapsulation of IMT within the nanoparticle matrix, with the drug transitioning to an amorphous state for enhanced dissolution. During Cell-Cell viability assays on LN229, glioblastoma cells were treated with IMT-loaded nanoparticles and showed a significantly enhanced inhibitory effect compared to free IMT. These hybrid nanoparticles demonstrated potential in reducing oxidative stress-induced cellular damage by mitigating reactive oxygen species (ROS). Thus, the prepared IMT hybrid nanoparticles showed higher cellular uptake and superior cytotoxicity compared to the plain drug. This study posits the IMT-PLGA-TPGS-DSPE PEG 2000-CSPLHNPs as a formidable and innovative drug delivery system for Glioblastoma Multiforme (GBM) treatment, warranting further exploration into their clinical application potential. Future work could involve conducting in vivo studies to evaluate the pharmacokinetics, biodistribution, and therapeutic efficacy of the IMT-PLGA-TPGS-DSPE PEG 2000-CSPLHNPs in animal models of Glioblastoma Multiforme (GBM). Additionally, further research may focus on optimizing the nanoparticle formulation for enhanced targeting capabilities, investigating long-term stability under varied storage conditions, exploring potential combination therapies to synergize with the nanoparticles, and assessing the scalability and manufacturability of the developed drug delivery system for potential clinical translation. Integration of advanced imaging techniques for real- time tracking and visualization of nanoparticle distribution within tumours could also be a promising direction for future investigations.

Hyaluronic Acid-Based Hybrid Nanoparticles as Promising Carriers for the Intranasal Administration of Dimethyl Fumarate.

Dimethyl fumarate (DMF), the first-line oral therapy for relapsing-remitting multiple sclerosis, is rapidly metabolized into monomethyl fumarate. The DMF oral administration provokes gastrointestinal discomfort causing treatment withdrawal. The present study aimed to develop an innovative formulation for DMF nasal administration. Lipid-polymer hybrid nanoparticles (LPNs) were developed to improve DMF stability, limiting gastrointestinal side effects and increasing brain bioavailability by nose-to-brain targeting application. DMF-loaded and unloaded LPNs with or without hyaluronic acid (HA) were prepared using the nanoprecipitation via magnetic/mechanical stirring technique. Particle morphology and surface properties were evaluated; drug content, viscosity, and mucoadhesion were determined. Physico-chemical stability of LPNs and DMF in the LPNs was also explored. In vitro DMF permeation experiments were performed utilizing the PermeaPad®. The cytotoxicity and cellular uptake studies were performed using RPMI 2650 and SK-N-BE2 cell lines. DMF nose-to-brain delivery was evaluated by intranasally administering DMF-loaded LPNs to rats. LPNs with average sizes of 120-250 nm and a negative zeta potential -17.3 to -43 mV were obtained, primarily influenced by the presence of HA. HA assured drug stability up to 60 days and promoting the in vitro permeation of DMF compared to the free-DMF. HA greatly improved the viscosity and mucoadhesive properties. LPNs with and without HA did not exhibit any cytotoxicity and showed a rapid cell uptake starting from 15min to 2h with a best internalization after 1h of treatment in both epithelial and neuronal cell lines. Nasal administration of DMF-loaded LPNs allowed to quantify up to about 12μg/mL of DMF in the rat cerebrospinal fluid. The results highlight the role of HA in improving LPNs properties and performance as carrier of DMF for nasal administration. In particular, LPNs appear able to enter neurons and monolayers of epithelial cells, allowing to promote the nose-to-brain DMF delivery.

Polymer-Based Nanoparticles as Efficient Non-Viral Vectors for Gene Delivery in CAR-T Cell Therapy

Chimeric Antigen Receptor (CAR)-T cell therapy has emerged as a revolutionary method in cancer immunotherapy, achieving notable success in treating hematological malignancies. However, its effectiveness in solid tumors is limited, and the therapy faces challenges such as severe toxicities and high production costs. Polymer-based nanoparticles (PNPs) are gaining attention as a non-viral gene delivery system that can help address these issues, providing greater safety, scalability, and cost-effectiveness compared to viral vectors. This mini-review delves into various types of PNPs, including cationic, biodegradable, and stimuli-responsive polymers, showcasing their mechanisms for cellular uptake and sustained gene expression in CAR-T cells. Innovations like lipid-polymer hybrid nanoparticles and combination therapies improve gene delivery efficiency and therapeutic outcomes. Despite progress, challenges, including toxicity and immunogenicity, remain, prompting strategies such as surface modifications and targeting ligands. Recent advancements illustrate the potential of hybrid nanoparticles in enhancing CAR-T therapies, particularly for solid tumors, highlighting their critical role in cancer immunotherapy advancements.

Nanotechnology-Enhanced Controlled Release Systems in Topical Therapeutics

Topical and transdermal drug delivery are alternative routes for medications facing challenges like solubility, stability, and first-pass metabolism. However, conventional immediate-release dosage forms delivered topically have drawbacks, including poor penetration and high side ef-fects. Controlled-release nanoparticles offer a promising solution, improving drug permeation and providing controlled release. This review examines recent advances, challenges, and pro-spects of controlled-release nanoparticles for topical drug delivery. Various types of nanoparti-cles, including lipid nanoparticles, Nanoemulsions, nanoemulgels, cubosome liposomes, poly-meric nanoparticles, solid-lipid nanoparticles, lipid-polymer hybrid nanoparticles, and nanostructured lipid carriers, carbon nanotubes, nanocomposites, and protein nanoparticles have been explored for their ability to encapsulate drugs, prolong drug release, and enhance skin permeation as well as improve therapeutic outcomes. Studies have demonstrated the effective-ness of these nanoparticles in improving sustained and controlled-release topical delivery of a wide range of drugs, including poorly soluble, low degree of skin penetration, low stability, and drugs with low bioavailability and biological products. Despite their potential benefits, challeng-es such as scalability, reproducibility, and safety concerns remain. Future research should ad-dress these challenges and explore novel strategies to improve efficacy and safety by converging with microneedles and 3D nanoparticles. Ultimately, controlled-release nanoparticles have the potential to revolutionize dermatological and transdermal drug delivery, leading to improved therapeutic outcomes and patient care.

Diving into RNAi Therapy: An Inhalable Formulation Based on Lipid-Polymer Hybrid Systems for Pulmonary Delivery of siRNA.

Here, a pulmonary formulation based on lipid-polymer hybrid nanoparticles carrying small interfering RNA (siRNA) was developed to realize a RNA interference-based therapy to treat respiratory diseases. Toward this aim, a new copolymer was synthesized, by functionalization of the α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide with 35 mol % of 1,2-bis(3-aminopropylamino)ethane, 0.4 mol % of fluorescent dye, and 4.5 mol % of poly(lactic-co-glycolic acid). This was used to encapsulate siRNA targeting the green fluorescent protein (siGFP), within a lipid shell made from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-distearoyl-sn-glycero-phosphoethanolamine-N-(polyethylene glycol)2000. siGFP-loaded lipid-polymer hybrid nanoparticles (LPHFNPs@siGFP) exhibited colloidal size (∼164 nm), positive ζ potential, high siRNA encapsulation efficiency (∼99%), and a core-shell morphology. They showed high cellular uptake and a gene silencing efficiency of ∼50% in human lung cancer cells expressing GFP. To address aerodynamic challenges, LPHFNPs@siGFP were spray-dried with trehalose, yielding spherical particles (∼3 μm) with 80% siRNA encapsulation efficiency, excellent aerosolization properties, and a gene silencing efficiency comparable to the fresh LPHFNPs@siGFP sample.

Treating Burn Infections With Topical Delivery of Positively Charged Norfloxacin-Loaded Lipid-Polymer Hybrid Nanoparticles.

Norfloxacin (NFX) is a wide-spectrum antibacterial agent that suffers from low water solubility and first-pass metabolism. This diminishes its oral bioavailability by 60-70%. This work aims to formulate a topical gel of NFX-loaded lipid polymer hybrid nanoparticles (NFX-LPHNPs) that combine the merits of liposomes and polymeric nanoparticles to overcome these problems. NFX-LPHNPs formulations were developed using Precirol ATO (lipid) and Eudragit RL100 (polymer). They were characterized for particle size, uniformity of distribution, entrapment efficiency, zeta potential, and in-vitro release. Box-Behnken design was applied to study sequentially different variables' impact on material attributes. Then the optimized formula was re-evaluated, and incorporated in an HPMC-gel formulation. The gel formulation was evaluated for its physical properties, in vitro-release, and antibacterial activity. NFX-LPHNPs exhibited particle sizes ranging from 28.92 to 730.30 nm. Particles were uniformly distributed with a positively charged surface (indicated by zeta potential with values from +3.91 to +60.2 mV). Formulations showed a % cumulative drug release of 87.9-100% in 8 h. The optimized formula showed a satisfied fit of measured-to-predicted responses with 159 nm particle size, 92.61% release and 79.2% entrapment efficiency. Gel formulation showed a sustained release over 24h. Antibacterial testing against Staphylococcus aureus, Acinetobacter baumannii and Pseudomonas aeruginosa revealed enhanced activity of NFX-LPHNPs against these pathogens compared to bare NFX loaded gel. These results illustrated the high potential of lipid-polymer hybrid nanoparticles to improve NFX activity against resistant pathogens common in burn infections. Moreover, the topical application helps overcome Norfloxacin oral-associated problems.

Lipid nanoparticles for pulmonary fibrosis: A comprehensive review.

Idiopathic pulmonary fibrosis (IPF) is a fatal progressive and irreversible ailment associated with the proliferation of fibroblast and accumulation of extracellular matrix (ECM) with gradual scarring of lung tissue. Despite several research studies, the treatments available are not efficient enough for the reversal of the disease and are constantly in progress. No drugs other than Pirfenidone and Nintedanib have been approved for the treatment of IPF, necessitating the exploration of novel therapeutic strategies. Recently, lipid-based nanoparticles (LNPs) have drawn more attention because of their potential to enhance the solubility of drugs, cross biological barriers of the lungs and specifically target lung fibrotic tissues, overcoming various challenges in treating IPF. LNPs offer a versatile platform to encapsulate a wide range of drugs, both hydrophilic and lipophilic, improving their bioavailability, allowing sustained release and reducing toxicity, which radiates their significant role in addressing the complexities of IPF. This review summarizes the pathogenesis and conventional treatment of idiopathic pulmonary fibrosis, along with their drawbacks. The review focuses on different types of lipid-based nanoparticles that have been tested in the treatment of idiopathic pulmonary fibrosis, including nanoemulsions, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, niosomes and lipid-polymer hybrid nanoparticles. The review also highlights the future prospects that can offer a potential approach for developing novel strategies to treat idiopathic pulmonary fibrosis.

Efficacy of Chitosan-N-Arginine Chitosomes in mRNA Delivery and Cell Viability Enhancement.

Cationic lipid-based carriers are recognized for their ability to complex with mRNA and effectively deliver the mRNA for vaccination and therapeutic purposes. However, the significant cytotoxicity of these carriers often restricts their practical application. In the present study, polymer-lipid hybrid nanoparticles, termed chitosomes, incorporating chitosan-N-arginine (CSA) with the DOTAP cationic lipid and the DOPE helper lipid, were synthesized and evaluated. The addition of CSA to the lipid formulations improved their physicochemical stability and enhanced mRNA complexation, resulting in high transfection rates in the HeLa and HEK293T cell lines. However, the transfection efficiency was low in the NIH-3T3 cell line, indicating a cell type-specific response to chitosomes. Importantly, CSA significantly reduced the cytotoxicity typically associated with DOTAP. Overall, the present study indicated that optimizing the ratio of CSA to DOTAP is crucial for developing mRNA nanocarriers to achieve high transfection efficiency and reduce cytotoxicity across different cell lines.

Lipid-Polymer Hybrid Nanoparticles in Microparticle-Based Powder: Evaluating the Potential of Methylprednisolone Delivery for Future Lung Disease Treatment via Inhalation.

Lipid-polymer hybrid nanoparticles (LPHNPs) offer a promising method for delivering methylprednisolone (MePD) to treat lung inflammation, addressing aggregation issues seen with polymer-only formulations. This study aimed to develop LPHNPs for MePD delivery, assessing their physicochemical properties, drug loading, cytocompatibility, and release profiles, ultimately enabling inhalable microparticle-based powder. The nanoparticles were formulated using α,β-poly(N-2-hydroxyethyl)-DL-aspartamide-g-Rhodamine B-g-poly(lactic acid) (PHEA-g-RhB-g-PLA) and phospholipids DPPC, DOTAP, and DSPE-PEG2000 in a 45:30:25 weight ratio. Their size, redispersion after freeze-drying, drug loading (DL%), and controlled release were evaluated. Cytocompatibility was assessed on 16-HBE cell lines, measuring anti-inflammatory effects via IL-6 and IL-8 levels. Spray drying was optimized to produce microparticles using mannitol (MAN), leucine (LEU), and N-acetylcysteine (NAC). The nanoparticles had a size of 186 nm and a DL% of 2.9% for MePD. They showed good cytocompatibility, significantly reducing IL-6 and IL-8 levels. Spray drying yielded microparticles with a fine particle fraction (FPF) of 62.3% and a mass median aerodynamic diameter (MMAD) of 3.9 µm. Inclusion of LPHNPs@MePD (0.25% w/v) resulted in FPF and MMAD values of 56.7% and 4.4 µm. In conclusion, this study described the production of novel inhalable powders as carriers for MePD-loaded nanostructures with favorable physicochemical properties, cytocompatibility, and promising aerosol performance, indicating their potential as an effective inhalable therapy for lung inflammation with corticosteroids, especially for treating chronic diseases.

Double Hydrophilic Hyperbranched Copolymer-Based Lipomer Nanoparticles: Copolymer Synthesis and Co-Assembly Studies.

Double hydrophilic, random, hyperbranched copolymers were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) utilizing ethylene glycol dimethacrylate (EGDMA) as the branching agent. The resulting copolymers were characterized in terms of their molecular weight and dispersity using size exclusion chromatography (SEC), and their chemical structure was confirmed using FT-IR and 1H-NMR spectroscopy techniques. The choice of the two hydrophilic blocks and the design of the macromolecular structure allowed the formation of self-assembled nanoparticles, partially due to the pH-responsive character of the DMAEMA segments and their interaction with -COOH end groups remaining from the chain transfer agent. The copolymers showed pH-responsive properties, mainly due to the protonation-deprotonation equilibria of the DMAEMA segments. Subsequently, a nanoscopic polymer-lipid (lipomer) mixed system was formulated by complexing the synthesized copolymers with cosmetic amphiphilic emulsifiers, specifically glyceryl stearate (GS) and glyceryl stearate citrate (GSC). This study aims to show that developing lipid-polymer hybrid nanoparticles can effectively address the limitations of both liposomes and polymeric nanoparticles. The effects of varying the ionic strength and pH on stimuli-sensitive polymeric and mixed polymer-lipid nanostructures were thoroughly investigated. To achieve this, the structural properties of the hybrid nanoparticles were comprehensively characterized using physicochemical techniques providing insights into their size distribution and stability.

Targeting SLITRK4 Restrains Proliferation and Liver Metastasis in Colorectal Cancer via Regulating PI3K/AKT/NFκB Pathway and Tumor-Associated Macrophage.

Liver metastasis is the major cause of death in colorectal cancer (CRC) due to the lack of effective treatment. To explore novel drivers of CRC liver metastasis, the transcriptomes of primary paracancerous, colorectal tumors and metastases from human patients are profiled. It is found that SLIT- and NTRK-like family member 4 (SLITRK4) is the top upregulated gene in liver metastases and is associated with worse overall survival of CRC patients. Multiple in vitro and in vivo models suggested SLITRK4 promoted CRC tumorigenesis, invasion, migration, and angiogenesis, and inhibition of it restrained CRC tumor growth and liver metastasis with a more profound effect on the tumor microenvironment (TME). Mechanistically, SLITRK4 overexpression significantly activated the PI3K/AKT/NFκB pathway, regulated extracellular matrix organization, and multiple cytokines expression. Furthermore, the results from coculture models and single-cell RNA sequencing analyses suggested SLITRK4 promoted tumor-associated macrophages (TAMs) infiltration and polarization. In addition, macrophage depletion significantly inhibited SLITRK4-induced liver metastasis in CRC. Finally, pharmacological inhibition of SLITRK4 by using lipid-polymer hybrid nanoparticles (NPs) for systemic siRNA delivery can effectively inhibit CRC liver metastasis. Taken together, these results pinpoint that SLITRK4 regulates CRC tumorigenesis and liver metastasis, and siRNA delivering NPs agents validate the therapeutic potential of targeting SLITRK4 in CRC.

SFRP1-Silencing GapmeR-Loaded Lipid-Polymer Hybrid Nanoparticles for Bone Regeneration in Osteoporosis: Effect of Dosing and Targeting Strategy.

Osteoporosis is a metabolic disorder characterized by the loss of bone mass and density. Nucleic acid-based therapies are among the most innovative approaches for osteoporosis management, although their effective delivery to bone tissue remains a challenge. In this work, SFRP1-silencing GampeR loaded-nanoparticles were prepared and functionalized with specific moieties to improve bone targeting and, consequently, therapeutic efficacy. SFRP1-silencing would promote osteoblastic differentiation by enhancing the WNT/β-catenin pathway and thus diminishing the progression of osteoporosis. A nucleic acid-based delivery system consisting of lipid-polymer hybrid nanoparticles (LPNPs) loading a GapmeR for SFRP1 silencing was developed and further functionalized with two bone-targeting moieties: a specific aptamer (Apt) for murine mesenchymal stem cells and an antiresorptive drug, namely alendronate (ALD). These systems were tested in vivo in osteoporotic mice at different dosage regimens to analyze dose dependence in bone-forming activity and potential toxicity. The quality of trabecular and cortical bone was assessed by both micro computed tomography (micro-CT) and histological and histomorphometric analyses. Early and late osteogenesis were quantified by immunohistochemistry. Results showed that functionalizing LPNPs loaded with an SFRP1-silencing GapmeR using both Apt and ALD improved bone quality and enhanced osteogenesis following a dose-effect relationship, as revealed by micro-CT, histological and immunohistochemical analyses. In contrast, non-functionalized LPNPs did not produce these effects. These findings highlight the relevance of proper targeting and dosage in nucleic acid-based therapeutics, proving to be crucial for exerting their therapeutic effect: a deficient targeting strategy and/or dosage may result in the therapeutic failure of an adequate gene therapy agent.

Self-assembled lipid-based nanoparticles for chemotherapy against breast cancer.

Self-assembled lipid-based nanoparticles have been shown to have improved therapeutic efficacy and lower toxic side effects. Breast cancer is a common type of malignant tumor in women. Conventional drugs such as doxorubicin (DOX) have shown low therapeutic efficacy and high drug toxicity in antitumor therapy. This paper surveys research on self-assembled lipid-based nanoparticles by categorizing them under three groups: self-assembled liposomal nanostructures, self-assembled niosomes, and self-assembled lipid-polymer hybrid nanoparticles. Subsequently, the structural features and operating mechanisms of each group are summarized individually along with examples of representative drugs from each group.

Stable Polymer-Lipid Hybrid Nanoparticles Based on mcl-Polyhydroxyalkanoate and Cationic Liposomes for mRNA Delivery.

Background/Objectives: The development of polymer-lipid hybrid nanoparticles (PLNs) is a promising area of research, as it can help increase the stability of cationic lipid carriers. Hybrid PLNs are core-shell nanoparticle structures that combine the advantages of both polymer nanoparticles and liposomes, especially in terms of their physical stability and biocompatibility. Natural polymers such as polyhydroxyalkanoate (PHA) can be used as a matrix for the PLNs' preparation. Methods: In this study, we first obtained stable cationic hybrid PLNs using a cationic liposome (CL) composed of a polycationic lipid 2X3 (1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride), helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine), and the hydrophobic polymer mcl-PHA, which was produced by the soil bacterium Pseudomonas helmantisensis P1. Results: The new polymer-lipid carriers effectively encapsulated and delivered model mRNA-eGFP (enhanced green fluorescent protein mRNA) to BHK-21 cells. We then evaluated the role of mcl-PHA in increasing the stability of cationic PLNs in ionic solutions using dynamic light scattering data, electrophoretic mobility, and transmission electron microscopy techniques. Conclusions: The results showed that increasing the concentration of PBS (phosphate buffered saline) led to a decrease in the stability of the CLs. At high concentrations of PBS, the CLs aggregate. In contrast, the presence of isotonic PBS did not result in the aggregation of PLNs, and the particles remained stable for 120 h when stored at +4 °C. The obtained results show that PLNs hold promise for further in vivo studies on nucleic acid delivery.

Timescale dependent homogeneous assembly of lipid-polymer hybrid nanoparticles in laminar mixing for enhanced lung cancer treatment

The homogeneity of core–shell structure lipid-polymer hybrid nanoparticles (HNPs) is crucial for efficient intracellular cargo delivery. While microfluidic techniques have been recognized for their capabilities in precisely controlling the size and drug encapsulation efficiency, there is little research exploring the impact of mass transfer behavior within microchannels on the homogeneous assembly process of HNPs. Here, we manipulated the laminar flow state within TrM device to achieve controlled assembly of HNPs and explored a timescale dependent assembly technique to ensure the homogeneity of folate modified HNPs (FHNPs). Our founding indicate that this method enabled the control over the growth kinetics of PLGA cores within a timescale (τgrow) of 1–15 ms. The homogeneous ligand assembly on the surface of FHNPs can only be achieved when τgrow exceeds the timescale of functional lipid coating (τcoating). Compared to conventional bulk mixing methods, this strategy significantly reduces the risk of heterogeneous assembly in FHNPs fabrication and ensures consistent reproducibility across batches. The homogeneous FHNPs (HFHNPs) fabricated through this method exhibit precise control over particle size (ranging from 75 nm to 150 nm), low polydispersity index, and consistent core–shell structure. Furthermore, this strategy enhances the density of available folate ligands on the surface of FHNPs. In subsequent in vitro and in vivo anti-tumor assays, the icariside Ⅱ (IS) loaded HFHNPs (IS@HFHNPs) exhibited enhanced cellular uptake and tumor accumulation behavior. the timescale dependent homogeneous assembly method for HNPs developed in this research presents a promising avenue for maintaining quality in the synthesis of self-assembly composite nanomecidine.

Development of biocompatible lipid-polymer hybrid nanoparticles for enhanced oral absorption of posaconazole: A mechanistic in vitro and in silico assessment

The current research focuses on the development of lipid-polymer hybrid nanoparticles (LPHNs) designed to enhance the solubility and bioavailability of posaconazole (PCZ). PCZ, an antifungal drug, faces challenges due to its poor water solubility, resulting in inconsistent absorption and limited bioavailability. LPHNs composed of stearic acid and poly-δ-decalactone (PDL) were successfully fabricated and characterized. The optimized formulation (P-LPHN4) exhibited a particle size of 104.0 nm, negative zeta potential (−38.9 mV), high drug loading (19.5 %), and efficient encapsulation (82.6 %). In vitro release studies demonstrated sustained drug release over 18 h, with P-LPHN4 displaying the highest drug release (92 %). Stability studies revealed good physical stability over 45 days with no significant changes in particle size, zeta potential, and PDI. In silico simulations using GastroPlus® predicted significantly improved intestinal absorption and systemic exposure for P-LPHN4 compared to the pure drug suspension in a simulated rat model. The model predicted a higher peak plasma concentration (Cmax) for P-LPHN4 (∼0.012 μg/mL) compared to the PCZ suspension (∼0.0058 μg/mL). The model identified the duodenum and jejunum as primary absorption sites for both formulations, with P-LPHNs showing significantly higher overall absorption (84.5 %) compared to the suspension (47.5 %). Simulation results revealed a dose-dependent increase in both Cmax and AUC with increasing oral P-LPHN4 dose, while Tmax remained unaffected. In conclusion, the developed posaconazole-loaded lipid-polymer hybrid nanoparticles (P-LPHN4) showed promising results in terms of enhanced drug release, stability, and bioavailability.

Lipid polymer hybrid nanoparticles against lung cancer and their application as inhalable formulation.

Lung cancer is a leading cause of global cancer mortality, often treated with chemotherapeutic agents. However, conventional approaches such as oral or intravenous administration of drugs yield low bioavailability and adverse effects. Nanotechnology has unlocked new gateways for delivering medicine to their target sites. Lipid-polymer hybrid nanoparticles (LPHNPs) are one of the nano-scaled delivery platforms that have been studied to exploit advantages of liposomes and polymers, enhancing stability, drug loading, biocompatibility and controlled release. Pulmonary administration of drug-loaded LPHNPs enables direct lung deposition, rapid onset of action and heightened efficacy at low doses of drugs. In this manuscript, we will review the potential of LPHNPs in management of lung cancer through pulmonary administration.

Inhaled Ivermectin-Loaded Lipid Polymer Hybrid Nanoparticles: Development and Characterization.

Ivermectin (IVM), a drug originally used for treating parasitic infections, is being explored for its potential applications in cancer therapy. Despite the promising anti-cancer effects of IVM, its low water solubility limits its bioavailability and, consequently, its biological efficacy as an oral formulation. To overcome this challenge, our research focused on developing IVM-loaded lipid polymer hybrid nanoparticles (LPHNPs) designed for potential pulmonary administration. IVM-loaded LPHNPs were developed using the emulsion solvent evaporation method and characterized in terms of particle size, morphology, entrapment efficiency, and release pattern. Solid phase characterization was investigated by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Using a Twin stage impinger (TSI) attached to a device, aerosolization properties of the developed LPHNPs were studied at a flow rate of 60 L/min, and IVM was determined by a validated HPLC method. IVM-loaded LPHNPs demonstrated spherical-shaped particles between 302 and 350 nm. Developed formulations showed an entrapment efficiency between 68 and 80% and a sustained 50 to 60% IVM release pattern within 96 h. Carr's index (CI), Hausner ratio (HR), and angle of repose (θ) indicated proper flowability of the fabricated LPHNPs. The in vitro aerosolization analysis revealed fine particle fractions (FPFs) ranging from 18.53% to 24.77%. This in vitro study demonstrates the potential of IVM-loaded LPHNPs as a delivery vehicle through the pulmonary route.

Rational design of solid lipid-polymer hybrid nanoparticles: An innovative glycoalkaloids-carrier with potential for topical melanoma treatment

Despite the promising potential of Solanum plant glycoalkaloids in combating skin cancer, their clinical trials have been halted due to dose-dependent toxicity and poor water solubility. In this study, we present a rational approach to address these limitations and ensure colloidal stability of the nanoformulation over time by designing solid lipid-polymer hybrid nanoparticles (SLPH). Leveraging the biocompatible and cationic properties of polyaspartamides, we employed a new polyaspartamide derivative (P1) as a raw material for this class of nanostructures. Subsequently, we prepared SLPH through a one-step process involving hot-melt emulsification followed by ultrasonication. The physicochemical properties of the SLPH were thoroughly characterized using dynamic light scattering (DLS), ζ-potential analysis, nanoparticle tracking analysis (NTA), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM). The optimized formulation exhibited long-term stability over six months under low temperatures, maintaining a particle size around 200 nm, a polydispersity index (PdI) lower than 0.2, and a ζ-potential between +35–40 mV. Furthermore, we evaluated the cytotoxic effect of the SLPH against human cutaneous melanoma cells (SK-MEL-28) compared to human foreskin fibroblast cells (HFF-1). Encapsulation of glycoalkaloids into the nanoparticles (SLPH-GE) resulted in a two-fold greater selective cytotoxic profile for melanoma cells than glycoalkaloids-free (GE). The nanoparticles disrupted the stratum corneum barrier with a penetration depth of approximately 77 μm. These findings underscore the potential of the developed nanosystem as an effective glycoalkaloid carrier with suitable colloidal and biological properties for further studies in topical treatment strategies for cutaneous melanoma.

Cationic lipid-coated bPEI/pDNA complexes: Correlation between physicochemical and morphological properties

Cationic lipid–polymer hybrid nanoparticles (cLPHNPs) complexed with nucleic acids, also named lipopolyplexes, have been developed as an alternative to nonviral vectors. These core/shell structures have been introduced to mitigate the limitations of cationic liposomes and biodegradable polymeric nanoparticles (NPs). The colloidal study of hybrid structures opens interesting perspectives for developing novel carriers for drug and gene delivery applications. Morphology aspects (size, lamellarity, and nucleic acid localization) and physicochemical properties of nonviral vectors influence gene delivery. Unraveling the structure of lipopolyplexes can enable their rational design toward enhanced gene delivery. Herein, we investigated the cationic LPHNPs loading plasmid DNA (pDNA) structure using dynamic light scattering, cryo-TEM, and pDNA accessibility assay. This study used pDNA as a genetic cargo for association with a cationic polymer, branched polyethylenimine (bPEI). It was found that the morphology of cationic LPHNP structures is influenced mainly by the formation process. Cationic LPHNPs formulated with EPC, DOPE, and cationic lipid DOTAP showed various degrees of multilamellarity depending on the production method. The addition of lipid dispersion to bPEI-pDNA anionic polyplex induced multilamellarity, while the preformed cationic liposome induced core/shell-like structures. Also, cLPHNPs showed better mechanical stability than polyplexes in a centrifugal vacuum concentrator (CVC) process. The physicochemical properties of cLPHNPs, formed in the presence of CL, were kept constant without significant changes. We believe these obtained colloidal data may be used to investigate hybrid-gene nanocarriers and their production process.