Nanoparticles For Delivery Research Articles

Mesoporous Biosilica Beads for Controlled Selenium Nanoparticle Delivery from Collagen‐Chitosan Scaffolds: Promoting Bone Formation and Suppressing Prostate Cancer Growth

The controlled delivery of selenium nanoparticles (Se‐NPs) is promising for bone cancer treatment due to their dual benefits in bone regeneration and tumor inhibition, yet achieving an optimal dosing regimen remains challenging. Natural mesoporous biosilica (BS) beads have shown promise for drug delivery due to their microporous structure. This study explores incorporating BS beads into collagen‐chitosan (Coll‐CS) scaffolds, known for bone repair, to control Se‐NP delivery. Two approaches are compared: loading Se‐NPs into BS beads before integrating them into Coll‐CS scaffolds versus directly loading Se‐NPs into Coll‐CS scaffolds. The scaffold properties, Se release kinetics, cytocompatibility, and effects on mesenchymal stem cells (MSCs) and prostate cancer cells (LNCaP) are evaluated. BS bead‐loaded scaffolds provide controlled Se‐NP release and enhanced mechanical properties compared to directly loaded scaffolds. Higher Se‐NP concentrations in BS‐loaded scaffolds effectively promote MSC osteogenic differentiation and mineralisation while inhibiting LNCaP cell viability. In contrast, low Se‐NP concentrations not only induce early osteogenic differentiation but also promote cancer cell proliferation, underscoring the need for optimal Se‐NP concentration and release. These findings suggest that BS bead‐loaded Coll‐CS scaffolds are a promising strategy for controlled Se‐NP delivery, addressing the dual challenges of bone formation and cancer recurrence prevention in bone cancer treatment.

Water-dispersible and Biocompatible Polymer-based Organic Upconversion Nanoparticles for Transdermal Delivery

Water-dispersible and Biocompatible Polymer-based Organic Upconversion Nanoparticles for Transdermal Delivery

Synthesis of Nanoparticles for Drug Delivery in Korea

Purpose: The aim of the study was to assess the synthesis of nanoparticles for drug delivery in Korea. Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries. Findings: The study indicated that the synthesis of nanoparticles for drug delivery has emerged as a promising strategy to enhance the efficacy and precision of therapeutic interventions. Nanoparticles offer several advantages, such as improved bioavailability, targeted delivery, and controlled release of drugs. Various methods are employed in their synthesis, including chemical reduction, sol-gel processes, and biological methods using natural organisms. These nanoparticles can be engineered to carry a wide range of drugs, including chemotherapeutics, antibiotics, and vaccines. Their small size allows them to navigate biological barriers and deliver drugs directly to specific tissues or cells, reducing side effects and improving treatment outcomes. However, challenges such as scalability, toxicity, and regulatory hurdles remain, necessitating further research to optimize their clinical applications. Implications to Theory, Practice and Policy: Brownian motion theory, nanoscale phenomena theory, thermodynamic theory of nanoparticle stability may be used to anchor future studies on the synthesis of nanoparticles for drug delivery in Korea. Practitioners in the field should prioritize the enhancement of synthesis techniques and the focus on biocompatibility and safety to improve the practical applications of nanoparticle drug delivery systems. To ensure the safe and effective use of nanoparticles in drug delivery, policymakers must establish clear guidelines and regulations governing their application.

Hepatocyte-Targeted Lipid Nanoparticle Delivery of HERC2 Plasmid Controls Drug-Induced Hepatotoxicity by Limiting β-Catenin-Regulated CYP2E1 Expression.

Understanding the molecular mechanisms that bridge hepatic inflammation and liver injury is crucial for developing effective therapeutic strategies for drug-induced liver injury (DILI) management. HECT domain and RCC1-like domain 2(HERC2) belongsto the large Herc family of ubiquitin E3 ligases, which are implicated in tissue development and inflammation. The observation reveals a pronounced HERC2 expression in specific hepatocyte subsets that proliferate in response to DILI in humans, prompting an investigation into the role of HERC2 in distinct DILI progression. Under the APAP challenge, liver-specific HERC2-deficient mice suffer more severe liver damage. Integrated single-cell RNA sequencing analysis unveils a negative correlation between HERC2 and CYP2E1, a vital metabolic enzyme for xenobiotics, in hepatocytes from APAP-challenged mice. Mechanistically, HERC2 interacts with β-catenin to promote its ubiquitination, thereby governing CYP2E1 transcriptional regulation. Targeted hepatic delivery of lipid nanoparticle-encapsulated HERC2-overexpressing plasmid markedly reduces liver damage caused by APAP overdose. Collectively, these findings elucidate a previously unrecognized protective role of HERC2 in protecting against acute liver injury associated with drug metabolism disorders, highlighting its potential as a therapeutic target in treating DILI.

Optimizing lipid nanoparticles for fetal gene delivery in vitro, ex vivo, and aided with machine learning

There is a clinical need to develop lipid nanoparticles (LNPs) to deliver congenital therapies to the fetus during pregnancy. The aim of these therapies is to restore normal fetal development and prevent irreversible conditions after birth. As a first step, LNPs need to be optimized for transplacental transport, safety on the placental barrier and fetal organs and transfection efficiency. We developed and characterized a library of LNPs of varying compositions and used machine learning (ML) models to delineate the determinants of LNP size and zeta potential. Utilizing different in vitro placental models with the help of a Random Forest algorithm, we could identify the top features driving percentage LNP transport and kinetics at 24 h, out of a total of 18 input features represented by 41 LNP formulations and 48 different transport experiments. We further evaluated the LNPs for safety, placental cell uptake, transfection efficiency in placental trophoblasts and fetal lung fibroblasts. To ensure the integrity of the LNPs following transplacental transport, we screened LNPs for transport and transfection using a high-throughput integrated transport-transfection in vitro model. Finally, we assessed toxicity of the LNPs in a tracheal occlusion fetal lung explant model. LNPs showed little to no toxicity to fetal and placental cells. Immunoglobin G (IgG) orientation on the surface of LNPs, PEGylated lipids, and ionizable lipids had significant effects on placental transport. The Random Forest algorithm identified the top features driving LNPs placental transport percentage and kinetics. Zeta potential emerged in the top driving features. Building on the ML model results, we developed new LNP formulations to further optimize the transport leading to 622 % increase in transport at 24 h versus control LNP formulation. To induce preferential siRNA transfection of fetal lung, we further optimized cationic lipid percentage and the lipid-to-siRNA ratio. Studying LNPs in an integrated placental and fetal lung fibroblasts model showed a strong correlation between zeta potential and fetal lung transfection. Finally, we assessed the toxicity of LNPs in a tracheal occlusion lung explant model. The optimized formulations appeared to be safe on ex vivo fetal lungs as indicated by insignificant changes in apoptosis (Caspase-3) and proliferation (Ki67) markers. In conclusion, we have optimized an LNP formulation that is safe, with high transplacental transport and preferential transfection in fetal lung cells. Our research findings represent an important step toward establishing the safety and effectiveness of LNPs for gene delivery to the fetal organs.

Developing an Arene Binuclear Ruthenium(II) Complex to Induce Ferroptosis and Activate the cGAS-STING Pathway: Targeted Inhibiting Growth and Metastasis of Triple Negative Breast Cancer.

To effectively inhibit the growth and metastasis of triple-negative breast cancer (TNBC), we developed a high-efficiency and low-toxicity arene ruthenium (Ru) complex based on apoferritin (AFt). To achieve this, we optimized a series of Ru(II) 1,10-phenanthroline-2,9-diformaldehyde thiosemicarbazone complexes by studying their structure-activity relationships to obtain an arene binuclear Ru(II) complex (C5) with significant cytotoxicity and high accumulation in the mitochondria of tumor cells. Subsequently, a C5-AFt nanoparticle (NPs) delivery system was constructed. We found that the C5/C5-AFt NPs effectively inhibited TNBC growth and metastasis with few side effects. The C5-AFt NPs improved the anticancer and targeting abilities of C5 in vivo. Moreover, we confirmed the mechanism by which C5/C5-AFt NPs inhibit tumor growth and metastasis via mitochondrial damage-mediated ferroptosis and activation of the cGAS-STING pathway.

Nanomaterial-Enhanced Microneedles: Emerging Therapies for Diabetes and Obesity.

Drug delivery systems (DDS) have improved therapeutic agent administration by enhancing efficacy and patient compliance while minimizing side effects. They enable targeted delivery, controlled release, and improved bioavailability. Transdermal drug delivery systems (TDDS) offer non-invasive medication administration and have evolved to include methods such as chemical enhancers, iontophoresis, microneedles (MN), and nanocarriers. MN technology provides innovative solutions for chronic metabolic diseases like diabetes and obesity using various MN types. For diabetes management, MNs enable continuous glucose monitoring, diabetic wound healing, and painless insulin delivery. For obesity treatment, MNs provide sustained transdermal delivery of anti-obesity drugs or nanoparticles (NPs). Hybrid systems integrating wearable sensors and smart materials enhance treatment effectiveness and patient management. Nanotechnology has advanced drug delivery by integrating nano-scaled materials like liposomes and polymeric NPs with MNs. In diabetes management, glucose-responsive NPs facilitate smart insulin delivery. At the same time, lipid nanocarriers in dissolving MNs enable extended release for obesity treatment, enhancing drug stability and absorption for improved metabolic disorder therapies. DDS for obesity and diabetes are advancing toward personalized treatments using smart MN enhanced with nanomaterials. These innovative approaches can enhance patient outcomes through precise drug administration and real-time monitoring. However, widespread implementation faces challenges in ensuring biocompatibility, improving technologies, scaling production, and obtaining regulatory approval. This review will present recent advances in developing and applying nanomaterial-enhanced MNs for diabetes and obesity management while also discussing the challenges, limitations, and future perspectives of these innovative DDS.

A Cell-Free Kinetic Analysis of Ionizable Lipid Hydrolysis.

The prolonged retention of ionizable lipids within the body limits the repeated dosing of lipid nanoparticles (LNPs) for nucleic acid delivery. While most ionizable lipids are primarily metabolized in the liver via the enzymatic hydrolysis of ester bonds, elimination half-lives can range from several hours to days. The development of compounds that undergo rapid biodegradation remains a major engineering challenge in the absence of standardized biodegradability assessments in the early stages of drug discovery. Here, we analyze and compare the hydrolysis kinetics of well-known ionizable lipids (ALC-0315, DLin-MC3-DMA, LP-01, L319, and SM-102) using optimized cell-free reactions monitored by 1H NMR. Unlike conventional analytical techniques, these NMR-based methods are universal and suitable for high-throughput screening. We demonstrate that enzyme-catalyzed and base hydrolysis reactions can predict whether ionizable lipids undergo fast or slow liver elimination, as our results are in alignment with prior pharmacokinetic studies. Furthermore, we show that the hydrolysis kinetics of ionizable lipids vary by several orders of magnitude depending on steric effects. This study provides a framework to expedite the discovery of rapidly degradable ionizable lipids, with implications for improving the therapeutic index of LNP-based drugs.

Tethered gold-liposome nanoparticles for iontophoresis-enhanced topical delivery for anti-inflammation

Topical delivery is a widely utilized drug administration route globally due to its convenience, non-invasiveness, and minimal drug metabolism. However, the skin barrier, particularly the stratum corneum (SC), poses a challenge by hindering drug absorption and permeation. To address this issue, green-synthesized gold nanoparticles (AuG) were loaded into liposomes to increase electron density and facilitate cathodal iontophoresis for topical drug delivery enhancement. Ginger rhizome extract served as a model hydrophobic compound encapsulated within the gold-liposomes to evaluate its anti-inflammatory effect. Our study demonstrated that the ginger-gold loaded liposomes (AuGL) enhanced cellular uptake of the hydrophobic payload and improved drug penetration through skin layers compared to conventional liposomes following iontophoresis. We investigated different ratios of gold nanoparticles to liposomes and characterized the nanoparticles using DLS, TEM, and FT-IR. Additionally, AuGL significantly inhibited nitric oxide release and TNF-α in RAW 264.7 cells. Furthermore, we formulated AuGL-loaded topical emulgel, which exhibited good stability under accelerated conditions. Our findings suggest that the AuGL combined with iontophoresis offers superior benefits for topical drug delivery, potentially enabling the treatment of skin inflammations and inflammation-related skin cancers.

Proteins-Based Nanoparticles for Benznidazole Enteric Delivery.

Chagas disease, caused by Trypanosoma cruzi (T. cruzi), affects millions worldwide, particularly in Latin America. Despite its prevalence, treatment options remain limited. Current drugs, such as benznidazole, cause adverse effects possibly due to ineffective administration. In this context, nanoparticles offer a promising solution to target and control drug delivery by leading the effector site and minimizing side effects. This article focuses on zein-casein-based nanoparticles (Bioparticles, BP) coated with Eudragit L100-55 (BP:EU) for enteric delivery of benznidazole. BP:EU structures are synthesized to minimize premature drug release in the stomach, promoting release in the small intestine. Physical characterization confirmed the successful synthesis of BP:EU and their pH-responsive trigger for drug release. These findings suggest that this material can be a promising approach for Chagas disease treatment, addressing challenges in benznidazole delivery that can lead to improved therapeutic responses.

Bioinspired core-shell microparticle for dual-delivery of prebiotic and probiotic for the treatment of ulcerative colitis

Lactiplantibacillus plantarum (LP) is a well-known probiotic strain that has a beneficial effect in preventing ulcerative colitis. However, delivering a sufficient number of viable LP to the colon still face challenges due to its vulnerability to the highly complex intestinal flora ecosystem. Herein, we present a centrifuge-driven micronozzle system designed for double-layered core-shell alginate microcapsules (DAM), which can serve as an effective carrier for dual delivery of resistant starch nanoparticles (RSNP, prebiotic) and LP (probiotics) for the treatment of colitis. This system enables precise loading of LP and RSNP within the core and shell regions of DAM, respectively. The resulting LP/RS@DAM exhibited a high encapsulation efficiency of LP (108 CFU per bead), in which the dense distribution of RSNP in the shell effectively protected LP against acidic conditions (pH 2) and maintained the cell viability up to 52 % even after long-term storage for 30 days. Furthermore, LP/RS@DAM effectively enhances the production of short-chain fatty acids, leading to a reduction in inflammatory cytokines and restoration of intestinal microbial diversity in dextran sulfate sodium (DSS)-induced colitis. We believe that this innovative approach would offer a potential solution for improving colitis management and paving the way for tailored therapeutic interventions in gastrointestinal disorders.

A promise of nose to brain delivery of bevacizumab intranasal sol-gel formulation substantiated in rat C6 glioma model.

Glioblastoma is one of the rapidly spreading cancers, with its potent malignancy often linked to pronounced angiogenesis within tumors. To mitigate this vascularization profile, bevacizumab (Avastin®), a monoclonal antibody, has been utilized for its antiangiogenic activity. However, its effectiveness is hindered by challenges in crossing the blood-brain barrier and the risk of off-target organ toxicity. Delivering drugs directly from the nose to the brain through the olfactory or trigeminal nerves bypassing the blood-brain barrier offers enhanced bioavailability and a more precise targeting strategy. To overcome these challenges, we aimed to develop bevacizumab in situ gel loaded mesoporous silica nanoparticles for intranasal delivery and further examine their pharmacokinetic and pharmacodynamic characteristics. The intranasal gel of mesoporous silica nanoparticles loaded with bevacizumab was optimized and formulated using a factorial and quality by design approach. In the case of bevacizumab mesoporous silica nanoparticles, lower particle size and most negative zeta potential were selected as quality target product profiles which is important for drug loading on the mesoporous silica nanoparticles and also transport of these nanoparticles across the nasal mucosa to the brain. A design space with a multidimensional combination of input variables and process parameters has been demonstrated to assure quality. To optimize the design space and achieve the desired quality standards, the base catalyst and surfactant concentration were chosen as the critical process parameters, while particle size and zeta potential were identified as the critical quality attributes. The novel formulation was assessed for physicochemical parameters such as particle size, zeta potential, entrapment efficiency, appearance, color, consistency, and pH. Additionally, studies on in vitro release, ex vivo permeation, stability, nasal toxicity, organ safety, and bioavailability were conducted. The efficacy study was conducted in an orthotopic murine glioblastoma rat model in which C6 Luc cells were instilled in the striatum of the rat's brain. In vivo, bioluminescence imaging of brain tumors was carried out to observe the tumor regression after treatment with the intranasal and intravenous bevacizumab formulation. Biochemical parameters and histopathology were performed for organ safety studies. The optimized intranasal formulation exhibited an average particle size of 318.8nm and a zeta potential of - 14.7mV for the mesoporous silica nanoparticles. The formulation also demonstrated an entrapment efficiency of 91.34% and a loading capacity of 45.67%. Further pharmacokinetic studies revealed that the optimized intranasal bevacizumab formulation achieved a significantly higher brain concentration Cmax = 147.9ng/ml, indicating improved bioavailability compared to rats administered with intravenous bevacizumab formulation (BEVATAS®), which had a Cmax of 127.2ng/ml. Moreover, this nanoparticle formulation entirely mitigated systemic exposure to bevacizumab. Organ safety evaluation of different biochemical parameters and histopathological analyses revealed that the intranasal bevacizumab-treated group was showing less off-target organ toxicity compared to the group treated with intravenous bevacizumab formulation. Subsequently, the efficacy of this nanosystem was evaluated in an orthotopic glioblastoma rat model, monitoring tumor growth over time through in vivo bioluminescence imaging and assessing anti-angiogenic effects. Twenty-one days post-induction, mesoporous silica nanoparticles loaded with bevacizumab in situ gel exhibited a marked reduction in average bioluminescence radiance (4.39 × 103) from day 7 (1.35 × 107) emphasizing an enhanced anti-angiogenic effect compared to the group treated with intravenous bevacizumab formulation which showed a gradual decrease in average bioluminescence radiance (4.82 × 104) from day 7 (1.42 × 107). These results suggest that the proposed novel formulation of mesoporous silica nanoparticles loaded bevacizumab in situ gel could serve as a promising avenue to enhance glioblastoma treatment efficacy, thereby potentially improving patient quality of life and survival rates significantly. Furthermore, the success of this delivery method could open new avenues for treating other neurological disorders, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and stroke. By providing effective brain-targeted therapies, this approach has the potential to revolutionize treatment options and improve outcomes for a broad spectrum of neurological conditions.

Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR-Cas9 ribonucleoprotein.

Lipid nanoparticle (LNP) delivery of clustered regularly interspaced short palindromic repeat (CRISPR) ribonucleoproteins (RNPs) could enable high-efficiency, low-toxicity and scalable in vivo genome editing if efficacious RNP-LNP complexes can be reliably produced. Here we engineer a thermostable Cas9 from Geobacillus stearothermophilus (GeoCas9) to generate iGeoCas9 variants capable of >100× more genome editing of cells and organs compared with the native GeoCas9 enzyme. Furthermore, iGeoCas9 RNP-LNP complexes edit a variety of cell types and induce homology-directed repair in cells receiving codelivered single-stranded DNA templates. Using tissue-selective LNP formulations, we observe genome-editing levels of 16‒37% in the liver and lungs of reporter mice that receive single intravenous injections of iGeoCas9 RNP-LNPs. In addition, iGeoCas9 RNPs complexed to biodegradable LNPs edit the disease-causing SFTPC gene in lung tissue with 19% average efficiency, representing a major improvement over genome-editing levels observed previously using viral or nonviral delivery strategies. These results show that thermostable Cas9 RNP-LNP complexes can expand the therapeutic potential of genome editing.

Chitosan nanoparticles for single and combinatorial delivery of 5-fluorouracil and ursolic acid for hepatocellular carcinoma

Chitosan nanoparticles for single and combinatorial delivery of 5-fluorouracil and ursolic acid for hepatocellular carcinoma

Paracyclophane-based ionizable lipids for efficient mRNA delivery in vivo

mRNA therapeutics utilizing lipid nanoparticle (LNP) delivery technology represent a medical innovation for the treatment of various diseases. Amine-derived ionizable cationic lipids have been regarded as the pivotal component of LNPs, which often utilize commercially available small amine molecules as their cores. Given that even minor changes in the structure of ionizable lipids can result in significant differences in the delivery performance, there is a growing need to redesign the lipid amine-cores to optimize mRNA therapy. Here, we rationally design and synthesize a library of 198 paracyclophane-based ionizable lipids (PILs), which are then formulated into LNPs for mRNA delivery in vitro and in vivo. The resulting PIL LNPs displayed favorable characteristics, including appropriate particle sizes, zeta potentials, mRNA binding capability, efficacious endosomal escape, and robust mRNA delivery in vitro. Tailoring the PIL structures further enables mRNA expression specifically in the liver or simultaneously across multi-organs in vivo. Notably, the optimized PIL LNPs demonstrate superior efficacy compared to the U.S. Food and Drug Administration (FDA) approved DLin-MC3-DMA LNPs following intravenous administration. Additionally, when administered intramuscularly, our PIL LNPs exhibit higher efficacy than the SM-102 and ALC-0315 LNPs that are employed in the coronavirus disease 2019 (COVID-19) mRNA vaccines. These findings demonstrate the potential of paracyclophane-based ionizable lipids in advancing mRNA therapeutics, particularly for liver-targeted drugs and vaccines.

Sustained release of proteins from contact lenses with porous annulus.

Ophthalmic drugs are administered to the front of the eye by eyedrops. The bioavailability of drugs delivered via eye drops is low due to tear turnover. Contact lenses can address some deficiencies of eye drops by sustaining the delivery of drugs, but commercial contact lenses have small pore sizes that cannot load biologics, which are becoming more common for treating ophthalmic diseases. This study aims to investigate novel poly(hydroxyethyl methacrylate) (pHEMA) lenses with transparent center and porous annulus for sustained release of model proteins. A novel hydrogel polymerization process was used to fabricate concentric, porous layer pHEMA hydrogel rods. The hydrogels were lathe cut into contact lenses which were explored for the delivery of proteins and gold nanoparticles. Lenses were characterized by partition coefficient and diffusivity, which was estimated by fitting experimental data to an analytical model. Transmittance measurements were made to compare transparency of porous lens centers to commercial contact lenses. Porous pHEMA lenses consisting of a concentric, porous layer made from 55% water content in precursor were successfully lathe cut into lenses with transparent center and opaque porous annulus. The porous lenses could load large model proteins of bovine serum albumin and human γ-globulin and provide sustained release. The core annular pHEMA contact lenses consisting of an outer annulus of opaque, porous pHEMA and an inner, center layer of clear, nonporous pHEMA can provide sustained delivery of biologics.

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

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

Optimization, Formulation, and Ex vivo Evaluation of Solid Lipid Nanoparticles for Transdermal Delivery of Diltiazem Hydrochloride.

Cardiac arrhythmia, is a medical condition that reduces the heart's efficiency in pumping blood, and can be fatal, requires long-term management with conventional drugs, despite their limited efficacy. Diltiazem hydrochloride, chosen as a model drug, has a short biological half-life and extensive metabolism. Administering drug through skin is challenging, particularly due to the penetration via stratum corneum. However, solid lipid nanoparticles as a particulate carrier system can enhance its permeation and bioavailability. The study aimed to develop a matrix type transdermal patch with diltiazem hydrochloride encapsulated in solid lipid nanoparticles Methods: The study used the solvent diffusion technique to prepare SLNs by mixing the drug and solid lipid in an organic phase at 80°C, then slowly adding it to an aqueous phase with continuous stirring for 45 minutes. The resulting nanodispersion was freeze-dried and analyzed for morphological studies, encapsulation efficiency & drug content. A patch was formulated using solvent evaporation technique, incorporating HPMC E50 (2% w/v), propylene glycol, and ethanolic oleic acid (1.5% v/v). SLNs loaded with diltiazem hydrochloride taken equivalent to diltiazem hydrochloride dose in the transdermal patch. The patch was then evaluated for In vitro and skin permeation studies. The result showed a positive correlation between lipid concentration and particle size. Probe sonication and homogenization increased particle size, while stirring speed reduced it. SEM and TEM images confirmed spherical particles with a size of 488.1±4.01nm and an entrapment efficiency of 55.03±1.99%. Drug release studies demonstrated 70.7% drug release from lipid matrix over 24 hrs. The formulated patch with uniform SLN distribution, had a drug content 89.37 ± 0.04% with a surface pH of 6.1 ± 0.53, close to skin pH. The uniformity of content in 3x3 patch estimated to be 14.587 ± 1.404 mg, close to the theoretical content 16.318 ± 1.08 mg, confirmed homogenous distribution of diltiazem hydrochloride SLNs throughout the patch diameter. Cumulative amount released from patch formulation at pH 5.6 and pH 7.4 was 518.1414μg/cm2 and 404.4466 μg/cm2. Synergistic flux enhancement was observed with oleic acid propylene glycol blend. Ex vivo study of the patch showed steady-state flux of 6.9 μg/cm2/hr, permeability coefficient 0.00362 cm/hr, diffusion coefficient 0.000103 cm/hr, cumulative drug permeation (Dmax) 814.885 μg after 24 hrs, and followed a Higuchi-matrix release model. The developed patch possessed improved bioavailability with reduced dosing and enhanced patient compliance.

Development of a pH-Sensitive Nanoparticle via Self-Assembly of Fucoidan and Protamine for the Oral Delivery of Insulin.

Objectives: Oral insulin delivery has received much attention over the past 20 years due to its high compliance. The aim of this study is to prepare nanoparticles for the oral delivery of insulin; Methods: Fucoidan and protamine were used to prepare a pH-sensitive nanoparticle via self-assembly. The secondary structure and in vitro stability of the nanoparticles were characterized using FTIR, XRD, ITC, and TEM. the nanoparticles had a controlled release effect on insulin in simulated intestinal fluid. The pre-liminary therapeutic effect on high-fat-fed type 2 diabetic mice; Results: When the fucoidan/protamine mass ratio was 10:3 (w/w), the particle size and zeta potential were 140.83 ± 1.64 nm and -48.13 ± 0.61 mV.The encapsulation efficiency of insulin was 62.97 ± 0.59%. The preliminary therapeutic effect on type 2 diabetic mice showed that the fasting blood glucose of diabetic mice decreased from 10.28 ± 0.88 mmol/L to 9.22 ± 0.64 mmol/L, the area under the curve value of oral glucose tolerance test was reduced by 11.70%, and the insulin se-cretion of diabetic mice was increased by 13.3%; Conclusions: The nanoparticles were prepared successfully by self-assembly. The empty and insulin-loaded nanoparticles remained stable in simulated gastric fluid, and the nanoparticles had a controlled release effect on insulin in simulated intestinal fluid. Moreover, insulin-loaded nanoparticles could relieve on type 2 diabetic mice.

Recent advances in surface decoration of nanoparticles in drug delivery

Recent advances in surface decoration of nanoparticles in drug delivery