Effective Delivery System Research Articles

Smart Accumulating Dual-Targeting Lipid Envelopes Equipping Oncolytic Adenovirus for Enhancing Cancer Gene Therapeutic Efficacy.

Systemic delivery of oncolytic adenovirus (oAd) for cancer gene therapy must overcome several limitations such as rapid clearance from the blood, nonspecific accumulation in the liver, and insufficient delivery to the tumor tissues. In the present report, a tumor microenvironment-triggered artificial lipid envelope composed of a pH-responsive sulfamethazine-based polymer (PUSSM)-conjugated phospholipid (DOPE-HZ-PUSSM) and another lipid decorated with epidermal growth factor receptor (EGFR) targeting peptide (GE11) (GE11-DOPE) was utilized to encapsulate replication-incompetent Ad (dAd) or oAd coexpressing short-hairpin RNA (shRNA) against Wnt5 (shWnt5) and decorin (dAd/LP-GE-PS or oAd/LP-GE-PS, respectively). In vitro studies demonstrated that dAd/LP-GE-PS transduced breast cancer cells in a pH-responsive and EGFR-specific manner, showing a higher level of transduction than naked Ad under a mildly acidic pH of 6.0 in EGFR-positive cell lines. In vivo biodistribution analyses revealed that systemic administration of oAd/LP-GE-PS leads to a significantly higher level of intratumoral virion accumulation compared to naked oAd, oAd encapsulated in a liposome without PUSSM or EGFR targeting peptide moiety (oAd/LP), or oAd encapsulated in a liposome with EGFR targeting peptide alone (oAd/LP-GE) in an EGFR overexpressing MDA-MB-468 breast tumor xenograft model, showing that both pH sensitivity and EGFR targeting ability were integral to effective systemic delivery of oAd. Further, systemic administration of all liposomal oAd formulations (oAd/LP, oAd/LP-GE, and oAd/LP-GE-PS) showed significantly attenuated hepatic accumulation of the virus compared to naked oAd. Collectively, our findings demonstrated that pH-sensitive and EGFR-targeted liposomal systemic delivery of oAd can be a promising strategy to address the conventional limitations of oAd to effectively treat EGFR-positive cancer in a safe manner.

Sodium Triphosphate Effect on Encapsulation of Vitamin B<sub>6</sub> into Chitosan-Alginate Nanoparticles and Its <i>In Vitro</i> Drug Release Study

The in-vitro drug release study of vitamin B6 encapsulated into sodium tripolyphosphate crosslinked chitosan-alginate (B6-TCA) nanoparticles aims to determine the effect of sodium tripolyphosphate on the encapsulation efficiency of vitamin B6 and effectiveness of the nanoparticles to release vitamin B6. The focus of this research is synthesizing and characterizing TCA nanoparticles to encapsulate vitamin B6 as an effective delivery system by studying the kinetics release of vitamin B6. The research resulted in the formation of coarse solid powder nanoparticles in yellowish-white color with a nanoparticle size of 22.55 nm. Sodium tripolyphosphate decreased the percentage of encapsulation efficiency in the B6-TCA nanoparticles as its concentration increased. However, the increasing sodium tripolyphosphate causes a slower release of vitamin B6 from nanoparticles. The encapsulation efficiency of vitamin B6 is 82.04%. The optimum composition of B6-TCA nanoparticles ratio is 2:1:1.5:2, where Korsmeyer-Peppas kinetics model suited its better with the Fickian diffusion mechanism of 0.989 and has the smallest reaction rate constant of 0.039 occurred within 6 h.

Redox-responsive degradation of antimicrobials with programmable drug release for enhanced antibacterial activity

The global crisis of antibiotic resistance has impelled the exigency to develop more effective drug delivery systems for the treatment of bacterial infection. The development of possessing high biocompatibility and targeted delivery of antimicrobials remains a persisting challenge. For programmable release of efficient antimicrobials in infection sites to enhance antibacterial activity, herein, we fabricated diselenide-bridged mesoporous organosilica nanoparticle-supported silver nanoparticles (Ag NPs) with high drug-loading capacity for the co-delivery of tobramycin (TOB) within one drug delivery system (Ag-MON@TOB (Se)). The resultant Ag-MON@TOB (Se) exhibited favorable biocompatibility due to its high stability in the physiological condition. Notably, such Ag-MON@TOB (Se) manifested a programmable structural destabilization to trigger sequential drug release in response to the oxidative stimuli within the bacterial infection microenvironment. In contradistinction to the oxidation-stable disulfide bond moieties within the framework of the nanocarrier (Ag-MON@TOB (S)), the Ag-MON@TOB (Se) with its programmed drug release behavior augmented prominent antibacterial therapy both in vitro and in vivo. This work represents a promising strategy for programmable drug release by harnessing a responsive degradable vehicle to enhance the treatment of bacterial infection.

Exploring Synthesis Strategies and Interactions between MOFs and Drugs for Controlled Drug Loading and Release, Characterizing Interactions through Advanced Techniques.

This study explores various aspects of Metal-Organic Frameworks (MOFs), focusing on synthesis techniques to adjust pore size and key ligands and metals for crafting carrier MOFs. It investigates MOF-drug interactions, including hydrogen bonding, van der Waals, and electrostatic interactions, along with kinetic studies. The multifaceted applications of MOFs in drug delivery systems are elucidated. The morphology and structure of MOFs are intricately linked to synthesis methodology, impacting attributes like crystallinity, porosity, and surface area. Hydrothermal synthesis yields MOFs with high crystallinity, suitable for catalytic applications, while solvothermal synthesis generates MOFs with increased porosity, ideal for gas and liquid adsorption. Understanding MOF-drug interactions is crucial for optimizing drug delivery, affecting charge capacity, stability, and therapeutic efficacy. Kinetic studies determine drug release rates and uniformity, vital for controlled drug delivery. Overall, comprehending drug-MOF interactions and kinetics is essential for developing effective and controllable drug delivery systems.

Picoplatin (II)-loaded chitosan nanocomposites as effective drug delivery systems: Preparation, mechanistic investigation of BSA/5-GMP/GSH binding and biological evaluations

The goal of the current study is to improve the characteristics and bioavailability of the drug picoplatin (PPt) by encapsulating it in chitosan nanoparticles (CS NPs) which allows for the targeted delivery of cytotoxic cargo to cancerous tissue, reducing toxic side effects and raising the therapeutic index. When picoplatin was delivered into the CS, it was able to produce an complex with CS (PPt@CS NPs) that had an appropriate particle size of 275 ± 10 nm, a reasonably low PDI of 0.15 ± 0.05, and high stability (ζ = −22.1 ± 0.3 mV). Since almost all pharmaceuticals work by binding to specific proteins or DNA, the in vitro binding mechanism and affinity of bovine serum albumin (BSA), low molecular building units of nucleic acids (5−GMP), and Glutathione (GSH) (considering that cisplatin resistance could be due to a reaction between cisplatin and GSH) to PPt and PPt@CS NPs were examined using stopped-flow and other spectroscopic approaches. Through two reversible processes, a rapid second-order binding followed by a slower first-order isomerization reaction, and a static quenching mechanism, PPt and PPt@CS NPs bind to BSA with relative reactivity of around (PPt)/(PPt@CS NPs) = 1/2.5. The 5−GMP interaction studies demonstrated that, in addition to changing the binding mechanism, PPt's encapsulation in CS increases its rate of reaction through coordination affinity. PPt interacted with 5-GMP via two reversible processes, a rapid second-order binding to phosphate followed by a slower first−order migration to the N7 of pyrimidine moiety. PPt@CS NPs showed weaker binding to GSH compared to PPt and hence PPt@CS NPs exhibits a lower resistance factor. It was also found that the in vitro drug release of PPt@CS NPs in PBS at pH 7.4 was steady, releasing 30% of the PPt in just 5 hours. Nonetheless, 75% of the release in a pH 5.4 solution containing 10 mM GSH—a solution that mimics the tumor microenvironment—shows that the PPt@CS NPs system is sensitive to GSH and specifically targets malignant tissue. The encapsulation of PPt in CS complex maintained its anticancer activity, as shown by an in vitro cell-survival assay on HepG2 cancer cell lines and also cleavage efficiency toward the minor groove of pBR322 DNA via the hydrolytic way. These findings collectively suggested that inclusion PPt in CS would be an effective strategy to formulate a novel picoplatin formulation intended for use as targeted anticancer treatment.

Colonic targeting insulin-loaded trimethyl chitosan nanoparticles coated pectin for oral delivery: In vitro and In vivo studies

Colon-targeted delivery offers several benefits for oral protein delivery, such as low proteolytic enzyme activity, natural pH, and extended residence time, which improve the bioavailability of the encapsulated protein. Therefore, we hypothesize that developing a novel colonic nanocarrier system based on modified chitosan, which enhances solubility at natural pH and is coated with a colon-degradable polymer, will provide an effective delivery system for oral insulin. This study aims to synthesize insulin-loaded pectin-trimethyl chitosan nanoparticles (Ins-P-TMC-NPs) as an oral insulin delivery system and evaluate their efficacy both in vitro and in streptozotocin-induced diabetic male rats. N-trimethyl chitosan (TMC), synthesized via a methylation method, was used to prepare insulin-TMC nanoparticles coated with pectin via the ionic gelation method. The nanoparticles were characterized for their physicochemical properties, cumulative release profile, and surface morphology. In vitro biological cytotoxicity and cellular uptake of the nanoparticles were evaluated against HT-29 cells using an MTT assay and fluorescent microscopy, respectively. The in vivo blood glucose-lowering effect was assessed in diabetic male Sprague–Dawley rats, with in vivo toxicity evaluated in the liver, spleen, duodenum, pancreas, and kidney through histological studies (H&E staining). The results showed that Ins-P-TMC-NPs were spherical, with an average size of 379.40 ± 40.26 nm, a polydispersity index of 24.10 ± 1.03 %, a zeta potential of +17.20 ± 0.52 mV, and a loading efficiency of 83.21 ± 1.23 %. Compared to uncoated TMC nanoparticles, Ins-P-TMC-NPs reduced insulin loss in simulated gastrointestinal fluid by approximately 67.23 ± 0.97 % and provided controlled insulin release in simulated colonic fluid. In vitro bioactivity studies revealed that Ins-P-TMC-NPs were non-toxic, with cell viability of 91.12 ± 0.91 %, and exhibited high cellular uptake in the HT-29 cell line with a fluorescence intensity of 37.80 ± 2.40. Furthermore, in vivo studies demonstrated a sustained reduction in blood glucose levels after oral administration, peaking after 8 h with a glucose reduction of 87 ± 1.03 %. Histological sections showed no signs of toxicity. Overall, the developed colon-targeted oral insulin delivery system shows great potential as a candidate for oral insulin administration.

A biodegradable lipid nanoparticle delivers a Cas9 ribonucleoprotein for efficient and safe in situ genome editing in melanoma

The development of melanoma is closely related to Braf gene, which is a suitable target for CRISPR/Cas9 based gene therapy. CRISPR/Cas9-sgRNA ribonucleoprotein complexes (RNPs) stand out as the safest format compared to plasmid and mRNA delivery. Similarly, lipid nanoparticles (LNPs) emerge as a safer alternative to viral vectors for delivering the CRISPR/Cas9-sgRNA gene editing system. Herein, we have designed multifunctional cationic LNPs specifically tailored for the efficient delivery of Cas9 RNPs targeting the mouse Braf gene through transdermal delivery, aiming to treat mouse melanoma. LNPs are given a positive charge by the addition of a newly synthesized polymer, deoxycholic acid modified polyethyleneimine (PEI-DOCA). Positive charge enables LNPs to be delivered in vivo by binding to negatively charged cell membranes and proteins, thereby facilitating efficient skin penetration and enhancing the delivery of RNPs into melanoma cells for gene editing purposes. Our research demonstrates that these LNPs enhance drug penetration through the skin, successfully delivering the Cas9 RNPs system and specifically targeting the Braf gene. Cas9 RNPs loaded LNPs exert a notable impact on gene editing in melanoma cells, significantly suppressing their proliferation. Furthermore, in mice experiments, the LNPs exhibited skin penetration and tumor targeting capabilities. This innovative LNPs delivery system offers a promising gene therapy approach for melanoma treatment and provides fresh insights into the development of safe and effective delivery systems for Cas9 RNPs in vivo. STATEMENT OF SIGNIFICANCE: CRISPR/Cas9 technology brings new hope for cancer treatment. Cas9 ribonucleoprotein offers direct genome editing, yet delivery challenges persist. For melanoma, transdermal delivery minimizes toxicity but faces skin barrier issues. We designed multifunctional lipid nanoparticles (LNPs) for Cas9 RNP delivery targeting the Braf gene. With metal microneedle pretreatment, our LNPs effectively edited melanoma cells, reducing Braf expression and inhibiting tumor growth. Our study demonstrates LNPs' potential for melanoma therapy and paves the way for efficient in vivo Cas9 RNP delivery systems in cancer therapy.

Encapsulation and release of salidroside in myofibrillar protein‑sodium alginate gel: Effects of different M/G ratios of sodium alginate

Myofibrillar protein‑sodium alginate (MP-SA) gels play a pivotal role in the development of functional food gels. Salidroside (SAL) is promising component but suffers from low bioavailability, necessitating effective delivery systems. This study introduces M/G ratio factor into classical theoretical MP-based gel models, and use for the SAL delivery. The findings indicate that SA significantly enhances gel properties and functions. Scanning electron microscopy, liquid chromatography, and low-field nuclear magnetic resonance confirmed that the addition of SA improved microstructure, water retention, and thus reduced SAL loss during processing. Digestion simulations revealed the influence of SA type on SAL release kinetics. Molecular docking showed that SA with lower M/G ratio binds more readily to MP, a key determinant of gel performance. These insights provide a novel theoretical basis for MP-SA gels and offer a new perspective on the delivery of bioactive compounds in functional foods.

INhaled Sedation versus Propofol in REspiratory failure in the Intensive Care Unit (INSPiRE-ICU1): protocol for a randomised, controlled trial

IntroductionSedation in mechanically ventilated adults in the intensive care unit (ICU) is commonly achieved with intravenous infusions of propofol, dexmedetomidine or benzodiazepines. Significant limitations associated with each can impact their...

Enhancing lutein stability and bioaccessibility with high internal phase emulsions stabilized by octenylsuccinylated starch

AbstractLutein possesses antioxidant properties and is a main component of the macular pigment, vital for infant eye and brain development. However, its use is constrained by its poor aqueous solubility and low stability. High internal phase emulsions (HIPEs) are valued in food development for encapsulating and protecting hydrophobic nutraceuticals. The objective of this study is to improve lutein's stability and bioaccessibility using HIPEs stabilized by biopolymer octenylsuccinylated starch (OSS). Three types of commercial OSS, including CAPSUL TA (CTA), HI‐CAP 100 (HC), and Purity Gum 2000, were tested for their emulsification properties in forming lutein HIPEs. Lutein HIPEs stabilized by 15%–25% CTA and 15%–30% HC had no phase separation and were selected for subsequent testing. After 21 days of storage at room temperature, lutein HIPEs showed higher lutein retention compared to free lutein. Lutein HIPEs stabilized with higher emulsifier concentrations (25% CTA and 30% HC) exhibited greater droplet diameter stability than those with lower concentrations. Additionally, lutein HIPEs significantly enhanced lutein retention under UV exposure and thermal stress. The in vitro bioaccessibility of lutein was highest in the HIPE stabilized by 20% CTA, reaching 54.36%. In conclusion, lutein HIPEs stabilized by 20% CTA demonstrated superior lutein stability and bioaccessibility, showing significant potential as an effective lutein delivery system.

Development of gallic acid loaded composite nanovesicles for the topical treatment of acne: optimization, characterization, and clinical investigation

Gallic acid (GA) proved to produce desired effects topically in the treatment of acne, through its antibacterial, anti-inflammatory and antioxidant characteristics. In the current work, nanovesicular systems; aspasomes loaded with GA were prepared, and evaluated on in-vitro and ex-vivo levels. Formulations were coated with chitosan due to its mucoadhesive properties. Results indicated that the size of the formulations ranged between 273.20 and 855.00 nm, with positively charged zeta potential ranging between 30.60 and 34.40 mV, EE% ranging between 57.651% and 95.20% and good stability after 3-months storage. The formulae provided a sustained drug release of 98.22% over 24 h, 5.4-fold higher ex-vivo skin deposition compared to GA solution, and powerful antioxidant potential compared to the control solution and appeared as spherical bilayer vesicles on being examined using transmission electron microscope. A clinical study was carried out on patients suffering from acne, where the reduction percent of comedones, inflammatory, total acne lesions and infiltrate was calculated. Results revealed that aspasomes exhibited reduction percentages of 72.35%, 80.33%, 77.95% and 90.01% ± for comedones, inflammatory lesions, total lesions, and infiltrate, respectively compared to control solution providing an effective topical delivery system for the management of acne.

Bioavailability enhancement of atazanavir sulphate using mixed micelles: in vitro characterization and in vivo pharmacokinetic study.

This study aims to enhance the oral bioavailability of atazanavir sulphate, a human immunodeficiency virus-1 protease inhibitor known for its poor oral absorption, by formulating mixed micelles using Soluplus® and Kolliphor HS 15. Mixed micelles were prepared through the thin film hydration technique. The micelles were characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, drug loading, and confirmed for atazanavir sulphate encapsulation via FTIR studies. In vitro release studies were conducted, and the morphology of the micelles was examined using TEM. Atazanavir sulphate mixed micelles exhibited a particle size of 62.92nm, PDI of 0.221, zeta potential of - 17.8mV, high entrapment efficiency (99.76 ± 1.06), and drug loading (14 ± 0.82). In vitro release studies demonstrated sustained release up to 12h, with maximum solubility observed at 2h under pH 1.2 conditions. TEM analysis revealed spherical micelle morphology. Oral administration of atazanavir sulphate mixed micelles showed a 1.23-fold increase in relative bioavailability compared to pure drug suspension. The formulation of mixed micelles using Soluplus® and Kolliphor HS 15 offers a promising strategy to improve the oral bioavailability of atazanavir sulphate. These findings suggest the potential utility of mixed micelles as an effective delivery system for atazanavir sulphate, offering enhanced therapeutic outcomes for patients.

Preparations, Applications, Patents, and Marketed Formulations of Nanoemulsions - A Comprehensive Review.

Nanoemulsions have emerged as versatile colloidal dispersions with promising applications in various fields, including pharmaceuticals, food, and cosmetics. These nano-sized emulsions, stabilized by surfactants, offer unique advantages such as enhanced ingredient penetration efficacy and versatile dosage forms. This article provides an extensive overview of nanoemulsions, covering their composition, methods of preparation, and applications in drug delivery, the food industry, and cosmetics. Various high-energy and low-energy methods for nanoemulsion preparation are discussed, along with their advantages and limitations. Additionally, the article highlights the potential of nanoemulsions in improving drug bioavailability, stability, and therapeutic efficacy, especially in oral, topical, parenteral, intranasal, ocular, and pulmonary drug delivery. Furthermore, nanoemulsions are explored as carriers for encapsulating flavoring agents, nutraceuticals, and natural preservatives in the food industry, as well as their use in cosmetic formulations. Current clinical trials involving nanoemulsions and recent patents in the field are also summarized, providing insights into ongoing research and development efforts. Lastly, a selection of marketed nanoemulsion formulations is presented, showcasing their practical applications and commercial availability. Overall, nanoemulsions hold great promise as effective delivery systems with broad applications across various industries.

Thermal stability and in vitro digestive behavior of Pickering emulsion stabilized by high-amylose starch nanocrystals

In this study, high-amylose starch (HAS) was processed using sulfuric acid-ultrasonic cross-linking to produce high-amylose starch nanocrystals (HASNC). These nanocrystals were used to stabilize Pickering emulsions and assess their effectiveness in encapsulating β-carotene. Normal starch nanocrystals (NSNC) were prepared similarly for comparison. The HASNC retained key HAS properties, such as heat and enzyme resistance, providing several advantages to HASNC-stabilized emulsions. First, after exposure to 100 °C heat and in vitro tests simulating the mouth and stomach, the HASNC-stabilized emulsions demonstrated significantly greater stability and higher β-carotene retention compared to the NSNC-stabilized emulsions. This enhanced stability is attributed to the lower gelatinization degree and increased resistance to α-amylase hydrolysis of HASNC, which provides stronger steric stabilization of the oil droplets. Second, during in vitro small intestine tests, the greater enzyme resistance of HASNC allowed for the formation of a denser barrier around the oil droplets, effectively preventing lipase and bile salts from contacting the oil droplets. This led to a reduced rate and extent of lipid digestion and facilitated a sustained-release effect. Consequently, HASNC, as a starch-based emulsifier, show great potential as an effective delivery system for the sustained release of bioactive compounds.

Optimizing Transdermal Patch Design: A Quality by Design Approach for Dysmenorrhea Relief.

This study explores the potential of transdermal patches as a systemic delivery system for donepezil (DPZ), aiming to circumvent hepatic first-pass metabolism and mitigate oral administration-associated side effects. DPZ, known for its poor solubility and adverse effects, is formulated into transdermal patches using a matrix-type approach with PVP K30 and HPMC K100 polymers alongside dimethyl sulfoxide as a plasticizer. Through solvent casting on a mercury surface, the patches are prepared and assessed for physical properties and drug-excipient interactions using FTIR analysis. The results demonstrate satisfactory physical characteristics, including appearance, weight variation, and tensile strength. Notably, formulations containing HPMC K100 (400 mg) and PVP K30 (300 mg) exhibit enhanced DPZ discharge, signifying their potential as an effective drug delivery system for mitigating DPZ-associated side effects.

Design, Development and Characterization of Nisoldipine Solid Lipid Nanoparticles: Statistical and Characterization Perspectives.

The objective of this study was to develop and characterize solid lipid nanoparticles (SLNs) loaded with Nisoldipine (NIS), aiming to enhance the drug’s bioavailability and provide a sustained release profile. SLNs were prepared using a solvent evaporation method and evaluated for several critical parameters. The superfluity test assessed the homogeneity of the SLN suspension, while particle size, drug entrapment efficiency, shapes, and surface morphology were analyzed using SEM/DLS/ TEM. Researchers studied the process of how drugs are released and performed in-vitro drug release tests to establish the substance’s release profile. HPLC and FT-IR were used to verify the drug’s chemical stability and encapsulation effectiveness. Stability studies assessed the formulation’s stability over time throughout different storage settings. The SLNs exhibited a high degree of homogeneity in the superfluity test, with no phase separation. The drug entrapment effectiveness was over 80%, and the typical particle size was 150-250 nm. Microscopy and transmission electron microscopy revealed that the SLNs had a flat, spherical top. NIS exhibited a regulated sequence of kinematics and prolonged release during dissolution investigations. FTIR and HPLC confirmed the stability and integrity of the drug within the SLNs. Stability studies indicated that the formulation remained stable over time. NIS-loaded SLNs show significant potential as an effective drug delivery system, offering enhanced bioavailability, sustained release, and excellent stability.

Mesenchymal stem cell-delivered paclitaxel nanoparticles exhibit enhanced efficacy against a syngeneic orthotopic mouse model of pancreatic cancer

Pancreatic cancer is considered the deadliest among various solid tumors, with a five-year survival rate of 13 %. One of the major challenges in the management of advanced pancreatic cancer is the inefficient delivery of chemotherapeutics to the tumor site. Even though nanocarriers have been developed to improve tumoral delivery of chemotherapeutics, less than 1 % of the drugs reach tumors, rendering inadequate concentration for effective inhibition of tumors. As a potential alternative, mesenchymal stem cells (MSCs) can effectively deliver their cargo to tumor sites because of their resistance to chemotherapeutics and inherent tumor tropism. In this study, we used MSCs for the delivery of dibenzocyclooctyne (DBCO)-functionalized paclitaxel (PTX)-loaded poly(lactide-co-glycolide)-b-poly (ethylene glycol) (PLGA) nanoparticles. MSCs were modified to generate artificial azide groups on their surface, allowing nanoparticle loading via endocytosis and surface conjugation via click chemistry. This dual drug loading strategy significantly improves the PTX-loading capacity of azide-expressed MSCs (MSC-Az, 55.4 pg/cell) compared to unmodified MSCs (28.1 pg/cell). The in vitro studies revealed that PTX-loaded MSC-Az, nano-MSCs, exhibited cytotoxic effects against pancreatic cancer without altering their inherent phenotype, differentiation abilities, and tumor tropism. In an orthotopic pancreatic tumor model, nano-MSCs demonstrated significant inhibition of tumor growth (p < 0.05) and improved survival (p < 0.0001) compared to PTX solution, PTX nanocarriers, and Abraxane. Thus, nano-MSCs could be an effective delivery system for targeted pancreatic cancer chemotherapy and other solid tumors.

Enhanced antidiabetic performance through optimized charantin-loaded nanostructured lipid carriers: Formulation and In vivo studies in diabetic mice

The hypoglycemic potential of charantin, a compound from Momordica charantia L., has been well-documented, but its pharmaceutical application faces challenges like poor solubility, low permeability, and suboptimal bioavailability. This study aimed to develop and optimize charantin-loaded nanostructured lipid carriers (Ch-NLCs) to enhance their antidiabetic efficacy. Using a 32 factorial design and high-pressure homogenization, Ch-NLCs were formulated with Precirol and Labrasol as solid and liquid lipids, respectively, combined with surfactants Tween 80 and Poloxamer 188. The optimization focused on key parameters such as particle size, entrapment efficiency (%EE), and zeta potential. FTIR confirmed the interaction between charantin and lipids, while DSC and XRD analyses showed the amorphous nature of Ch-NLCs. The optimized Ch-NLCs exhibited a particle size of 221.0 nm, an %EE of 81.89 %, and a zeta potential of −24.42 mV. In vitro release studies demonstrated a sustained release profile of charantin from the NLCs. In vivo studies on streptozotocin (STZ)-induced diabetic mice revealed significantly enhanced antidiabetic effects of Ch-NLCs compared to pure charantin. Specifically, Ch-NLCs led to substantial reductions in blood glucose levels, total cholesterol (T-Cho), low-density lipoprotein (LDL) and glycosylated hemoglobin (HbA1c) levels, while improving high-density lipoprotein (HDL). These findings highlight the potential of Ch-NLCs as an effective delivery system for charantin in diabetes management. In conclusion, the study successfully engineered and optimized Ch-NLCs, demonstrating their superior pharmacokinetic profiles over pure charantin. These results suggest that Ch-NLCs could be a promising candidate for effective diabetes management, warranting further clinical investigation to confirm their therapeutic potential in human subjects.

Lipid-Conjugated Reduced Haloperidol in Association with Glucose-Based Nanospheres: A Strategy for Glioma Treatment.

Aggressive glioma exhibits a poor survival rate. Increased tumor aggression is linked to both tumor cells and tumor-associated macrophages (TAMs), which induce pro-aggression, invasion, and metastasis. Imperatively, for effective treatment, it is important to target both glioma cells and TAMs. Haloperidol, a neuropsychotic drug, avidly targets the sigma receptor (SR), which is expressed in higher levels in both the cell types. Herein, we present the development of a novel cationic lipid-conjugated reduced haloperidol (±RHPC8), which aims to mediate the SR-targeted antiglioma effect. Hypothetically, ±RHPC8 would act simultaneously as an SR-targeting ligand and anticancer agent. As the blood-brain barrier (BBB) obstructs direct targeting of in situ glioma, we used BBB-crossing glucose-based carbon nanospheres (CSPs) to deliver ±RHPC8 within the glioma tumor-bearing mouse brain. The resultant ±RHPC8-CSP nanoconjugate targeted SR-expressing glioma cells. In both orthotopic and subcutaneous mouse tumor models, ±RHPC8-CSP prolonged survival and regressed tumors compared to other treated groups. Notably, ±RHPC8-CSP was significantly taken up by SR-expressing TAMs thus resulting in macrophage polarization from M2 to M1, as exhibited by markedly reduced expression of immunosuppressive cytokines released by TAMs, including TGF-β, IL-10, and VEGF. In conclusion, the designed ±RHPC8-CSP nanoconjugate presented an effective nanodrug delivery system for brain cancer treatment.

Dual folate/biotin-decorated liposomes mediated delivery of methylnaphthazarin for anti-cancer activity

Chemotherapy is an effective strategy for mitigating the global challenge of cancer treatment, which often encounters drug resistance and negative side effects. Methylnaphthazarin (MNZ), a natural compound with promising anti-cancer properties, has been underexplored due to its poor aqueous solubility and low selectivity. This study introduces a novel approach to overcome these limitations by developing MNZ-encapsulating liposomes decorated with folate and biotin (F/B-LP-MNZ). This dual-targeting strategy aims to enhance the anti-cancer efficacy and specificity of MNZ delivery. Our innovative F/B-LP-MNZ formulation demonstrated excellent physicochemical properties, stability, and controlled drug release profiles. In vitro studies revealed that MNZ-loaded liposomes attenuate the toxicity associated with free MNZ while F/B-LP-MNZ significantly increased cytotoxicity against HeLa cells, which express high levels of folate and biotin receptors, compared to non-targeted liposomes. Enhanced cellular uptake and improved dynamic flow attachment further confirmed the superior specificity of F/B-LP in targeting cancer cells. Additionally, our results revealed that F/B-LP-MNZ effectively inhibits HeLa cell migration and adhesion through EMT suppression and apoptotic induction, indicating its potential to prevent cancer metastasis. These findings highlight the potential of dual folate and biotin receptors-targeting liposomes as an effective delivery system for MNZ, offering a promising new avenue for targeted cancer therapy.