Water-soluble Drugs Research Articles

Preparation of Ketoconazole-loaded Nanoemulsions for Ophthalmic Delivery: Characterization and In-vitro Antifungal Activity Evaluation

Background: Nanoemulsions (N.E.s) capable of ocular bioavailability elevation can be used for poor water-soluble drugs such as ketoconazole (K.Z.). The current investigation was designed for the purpose of overcoming this issue by developing K.Z. containing N.E.s for ophthalmic drug delivery with appropriate therapeutic efficiency. Methods: The preparation of ketoconazole N.E.s was performed by the low-energy technique. According to the phase diagram, three stable formulations were selected for more physicochemical analyses, including particle size, polydispersity index, pH, refractive index and viscosity. Finally, drug release patterns and in-vitro antifungal activity were assessed for the final selected formulation. Results: The developed N.E. formulations with droplet sizes less than 20 nm showed appropriate physicochemical characteristics for ocular delivery. The selected formulation released 100% of the encapsulated drug during 24 h. Moreover, antifungal assessments showed that prepared N.E. had acceptable in-vitro antifungal activity. Conclusions: Based on our findings, it can be concluded that N.E.s could be applied as effective carriers for the ophthalmic delivery of ketoconazole.

Preparation and Investigation of a Nanosized Piroxicam Containing Orodispersible Lyophilizate

Non-steroidal anti-inflammatory piroxicam (PRX) is a poorly water-soluble drug that provides relief in different arthritides. Reducing the particle size of PRX increases its bioavailability. For pediatric, geriatric, and dysphagic patients, oral dispersible systems ease administration. Moreover, fast disintegration followed by drug release and absorption through the oral mucosa can induce rapid systemic effects. We aimed to produce an orodispersible lyophilizate (OL) consisting of nanosized PRX. PRX was solved in ethyl acetate and then sonicated into a poloxamer-188 solution to perform spray-ultrasound-assisted solvent diffusion-based nanoprecipitation. The solid form was formulated via freeze drying in blister sockets. Mannitol and sodium alginate were applied as excipients. Dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) were used to determine the particle size. The morphology was characterized by scanning electron microscopy (SEM). To establish the crystallinity, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used. A disintegration and in vitro dissolution test were performed. DLS and NTA presented a nanosized PRX diameter. The SEM pictures showed a porous structure. PRX became amorphous according to the XRPD and DSC curves. The disintegration time was less than 1 min and the dissolution profile improved. The final product was an innovative anti-inflammatory drug delivery system.

Development of deep eutectic solvent systems and their formulation: Assessment of solubilization potential on poorly water-soluble drugs

Development of deep eutectic solvent systems and their formulation: Assessment of solubilization potential on poorly water-soluble drugs

Solid self-emulsifying casein carrier for the improvement on the oral bioavailability of simvastatin

Simvastatin (SV) is a statin drug that can effectively control cholesterol and prevent cardiovascular diseases. However, SV is water-insoluble, and poor oral bioavailability (<5 %). Solid self-emulsifying carrier system is more stable than liquid emulsions, facilitating to improve the solubility and bioavailability of poorly soluble drugs. In the present study, a solid self-emulsifying carrier stabilized by casein (Cas-SSE) was successfully used to load SV to improve its solubility in water, by formulation selection and emulsification process optimization. Compared with oral tablets, the release of SV from Cas-SSE was significantly enhanced in artificial intestinal fluid. Furthermore, everted gut sac experiments indicated some water-soluble dispersing agents such as hydroxyethyl starch (HES), were not conducive to drug absorption. Pharmacokinetic studies suggested Cas-SSE without dispersing agent has much higher relative bioavailability (184.1 % of SV and 284.5 % of simvastatin acid) than SV tablet. The present work suggests Cas-SSE is a promising drug delivery platform with good biocompatibility for improving oral bioavailability of poorly water-soluble drugs.

In vitro lipolysis model to predict food effect of poorly water-soluble drugs itraconazole, rivaroxaban, and ritonavir

It is desirable to predict positive food effect of oral formulations due to food mediated dissolution enhancement of lipophilic drugs. The objective was to assess the ability of in vitro lipolysis to anticipate a positive food effect. Tested formulations included rivaroxaban and itraconazole, where some formulations, but not all, exhibit a positive food effect in vivo in humans. Amorphous solid dispersion formulations of ritonavir, which exhibit a negative food effect in vivo in humans, were also studied. Fe-lipolysis and Fa-lipolysis media representing fed and fasted intestinal conditions were used. Results show frequent agreement between in vitro lipolysis predictions and in vivo human outcomes. For rivaroxaban, food effect of unformulated active pharmaceutical ingredient (API) and products were correctly predicted where 2.5mg and 10mg strengths did not show any food effect; however, 20mg did show a positive food effect. For itraconazole, all four products were correctly predicted, with Sporanox, Sempera, and generic capsules having a food effect, but Tolsura not having a positive food effect. For ritonavir, lipolysis predicted a positive food effect for API and Norvir tablet and powder, but Norvir products have negative food effect in vivo in humans. Overall, the lipolysis model showed favorable predictability and merits additional evaluation.

Compritol®-based solid lipid nanoparticles of desvenlafaxine prepared by ultrasonication-assisted hot-melt encapsulation to modify its release.

Aims: Desvenlafaxine (DES) in conventional dosage forms shows initial burst release after oral administration, leading to exaggeration of its side effects. These side effects can be overcome by a sustained-release dosage form using the chemically inert, low-melting-point lipid Compritol® 888 ATO, as it reduces initial burst release. Materials & methods: The potential of DES-loaded solid lipid nanoparticles (DES-SLNs) synthesized by ultrasonication-assisted hot-melt encapsulation to modify the release of DES was investigated. Results: The entrapment efficiency of DES-SLNs was 65.90% with the in vitro release profile showing a sustained-release behavior achieving 81% cumulative release within 16h without initial burst release. Conclusion: DES-SLNs are a potential carrier for sustained release of water-soluble antidepressant drugs such as DES.

Insights into the Mechanism of Enhanced Dissolution in Solid Crystalline Formulations

Solid dispersions are a promising approach to enhance the dissolution of poorly water-soluble drugs. Solid crystalline formulations show a fast drug dissolution and a high thermodynamic stability. To understand the mechanisms leading to the faster dissolution of solid crystalline formulations, physical mixtures of the poorly soluble drugs celecoxib, naproxen and phenytoin were investigated in the flow through cell (apparatus 4). The effect of drug load, hydrodynamics in the flow through cell and particle size reduction in co-milled physical mixtures were studied. A carrier- and drug-enabled dissolution could be distinguished. Below a certain drug load, the limit of drug load, carrier-enabled dissolution occurred, and above this value, the drug defined the dissolution rate. For a carrier-enabled behavior, the dissolution kinetics can be divided into a first fast phase, a second slow phase and a transition phase in between. This study contributes to the understanding of the dissolution mechanism in solid crystalline formulations and is thereby valuable for the process and formulation development.

Characterization and Drug Release Properties of Curcumin Loaded Native and Nano‐Sized Starches of Pigeon Pea (Cajanus cajan) and Bambara Nut (Vigna subterranean)

AbstractStarches from underutilized sources such as Bambara nut (BAM) and pigeon pea (PP) can serve as new sources of starch. Starch nanoparticles (SNP) of BAM (BAMnp) and PP (PPnp) are prepared by nanoprecipitation. The physicochemical and pasting properties of the native and SNP are evaluated. The scanning electron microscopy, fourier transform infrared spectroscopy (FTIR), X‐ray diffraction (XRD), drug loading, and release studies of curcumin‐loaded starches and SNP are carried out. The flow, swelling, and solubility of the native starches improve with nanoparticle fabrication. Setback viscosities of the starches are in the order PPnp &lt; BAMnp &lt; PP &lt; BAM. The integrity of the starch granules is maintained after modification. The FTIR of loaded starches shows no interaction between the entities. Reduction in crystallinity of the SNP is observed in the XRD diffractogram. The drug loading efficiency of BAM, PP, BAMnp, and PPnp are 48.55 ± 0.11, 49.00 ± 0.11, 55.44 ± 0.40, and 54.72 ± 0.11, respectively. The drug release is improved when curcumin is loaded on the SNP. The release after 6 h is 33%, 25%, and 2% for BAMnp, PPnp, and pure curcumin, respectively. The properties of the SNP showed that they are potential candidates for the delivery of curcumin, a poorly water soluble drug.

A Comprehensive Guide to the Development, Evaluation, and Future Prospects of Self-nanoemulsifying Drug Delivery Systems for Poorly Water-soluble Drugs.

Self-Nano Emulsifying Drug Delivery Systems (SNEDDS) are novel formulations that can enhance the solubility and bioavailability of poorly water-soluble drugs. SNEDDS are composed of lipids, surfactants, co-solvents, and drugs and can spontaneously form nanoemulsions when mixed with water under mild agitation. SNEDDS can be formulated as liquid or solid dosage forms and can improve drug absorption by increasing the interfacial area, protecting the drug from degradation, and facilitating lymphatic transport. SNEDDS is characterized by various parameters such as particle size, zeta potential, droplet morphology, emulsification efficiency, drug solubility, and stability. SNEDDS offers several advantages over conventional dosage forms, such as dose reduction, faster onset of action, reduced variability, versatility, and ease of formulation. However, SNEDDS also face some limitations and challenges, such as drug precipitation, cost-effectiveness, compatibility with capsule shells, and lack of predictive in vitro models. SNEDDS has a promising future in the field of pharmaceuticals, especially for personalized medicine and targeted drug delivery.

Nanoemulgel: An Innovative Carrier for Drug Delivery of Poorly Water-Soluble Drugs

Abstract:: Recently, the delivery of hydrophobic/ poorly water-soluble drugs has been a difficult task. Various approaches have been developed to counter the former and other main issues, such as solubility, bioavailability, etc. However, only a few formulations have successfully addressed the problems and nanoemulgels are a standout among them. The nanoemulgel drug delivery approach combines multiple benefits associated with emulsion and gel technologies to improve active moiety solubility, bioavailability, and longevity. The article discusses the present status of nanoemulgel research and development, including its preparation methods and characterization techniques. Additionally, the possible uses of nanoemulgel in targeted drug delivery and cosmetic/ personal care products are discussed. Overall, nanoemulgel technology has shown significant promise as a novel approach to augment the transport of water-insoluble moieties. With further research as well as development, it is expected to have a substantial impact on the pharmaceutical and cosmetic industries. This inclusive review highlighted the role of nanoemulgels as a promising carrier for drug delivery, with an overview of a few illustrations supporting the cause.

In-vitro Lipolysis, Stability and Pharmacodynamic Study of Cilnidipine Loaded Self-emulsifying Drug Delivery System

Aim: The aim of this research work was to investigate the potential ability of cilnidipineloaded- Self-Emulsifying Drug Delivery System (SEDDS) to improve the solubility and oral bioavailability of cilnidipine. background: The limited oral bioavailability of BCS class II drugs restricts the clinical utility of drugs. Self-emulsifying drug delivery systems (SEDDS) are widely used for poorly water-soluble drugs to enhance their solubility and oral bioavailability. Background: The therapeutic value of drugs is constrained by the low oral bioavailability of BCS class II drugs. In order to improve the solubility and oral bioavailability of poorly water-soluble drugs, SEDDS are frequently utilised. Methods: To develop the cilnidipine-loaded-SEDDS formulation, Canola oil as the oil phase, tween 80 as the surfactant, and PEG 300 as the co-surfactant were used. The SEDDS formulation was evaluated based on stability study per ICH guidelines, drug precipitation during in-vitro lipolysis study under fasted and fed state, and in vivo pharmacodynamic study in Wistar rats. The content of the drug was determined by assay of SEDDS formulation using the official method of cilnidipine. Result: The pharmacodynamic study demonstrated that cilnidipine-loaded SEDDS formulation significantly produced a rapid antihypertensive effect (within 2 h) that lasted for 24 h in comparison to drug suspension. During the in vitro lipolysis study, the concentration of the drug recovered from the aqueous phase under both fasted and fed state was more than 90% after 10 minutes, with a minute amount of drug involved in precipitation. At stability conditions of 30±2 °C/65±5%RH for a duration of six months, the SEDDS formulation was found to be stable. The content of cilnidipine in the SEDDS formulation was found to be 98.4%. Conclusion: A BCS class-II drug's oral bioavailability and dissolution might be improved using the self-emulsifying drug delivery method.

Preparation and characterization of citreorosein nanoparticles with improved bioavailability and cytotoxic potential

The present study was designed to improve the aqueous solubility and dissolution rate of citreorosein, a poorly water soluble drug, by producing its nanoparticles (NPs) using an “antisolvent precipitation with a syringe pump” (APSP) method. Various process parameters including flow rate, stirring speed, temperature, drug concentration and solvent-antisolvent ratio were investigated and optimized to obtain the smallest particle size of citreorosein. The prepared NPs were subjected to different analytical techniques such as SEM, FTIR, XRD and DLS. The NPs were tested for different dissolution parameters including difference (f1) and similarity factors (f2), dissolution efficiency (DE) and mean dissolution time (MDT). The antioxidant potential ofcitreorosein and its NPs were evaluated using DPPH, ABTS, and FRAP models, while their cytotoxicity was tested on various cancer cell lines such as breast (MDA-MB-231), lung (A549) and liver (HepG2), using the MTT assay. The specificity of the test compound was investigated against two normal human primary epithelial cells including renal (HRPTEpiC) and alveolar (HPAEpiC) cells. DLS analysis revealed that the prepared NPs were less than 200 nm in size while SEM and XRD confirmed their rod shape and amorphous nature, respectively. Citreorosein-NPs exhibited enhanced solubility and dissolution rate in all medias as compared to pure citreorosein. The NPs displayed significant antioxidant effects against ABTS, DPPH and FRAP models, with IC50 values of22.6, 21.45 and 27.30 µg/ml, respectively. Moreover, it showed significant cytotoxic activity against MDA-MB-231, A549 and HepG2 cells, with IC50 values of 3.45, 4.5 and 6.23 µg/ml, respectively. Furthermore, the NPs demonstrated high selectivity index values for the aforementioned cell lines as compared to reference drugs. This study demonstrated that APSP method successfully produced citreorosein-NPs and hence, showed better aqueous solubility, dissolution rate, antioxidant and cytotoxic activities than the pure compound

Dual-targeting tigecycline nanoparticles for treating intracranial infections caused by multidrug-resistant Acinetobacter baumannii

Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is a formidable pathogen responsible for severe intracranial infections post-craniotomy, exhibiting a mortality rate as high as 71%. Tigecycline (TGC), a broad-spectrum antibiotic, emerged as a potential therapeutic agent for MDR A. baumannii infections. Nonetheless, its clinical application was hindered by a short in vivo half-life and limited permeability through the blood–brain barrier (BBB). In this study, we prepared a novel core–shell nanoparticle encapsulating water-soluble tigecycline using a blend of mPEG-PLGA and PLGA materials. This nanoparticle, modified with a dual-targeting peptide Aβ11 and Tween 80 (Aβ11/T80@CSs), was specifically designed to enhance the delivery of tigecycline to the brain for treating A. baumannii-induced intracranial infections. Our findings demonstrated that Aβ11/T80@CSs nanocarriers successfully traversed the BBB and effectively delivered TGC into the cerebrospinal fluid (CSF), leading to a significant therapeutic response in a model of MDR A. baumannii intracranial infection. This study offers initial evidence and a platform for the application of brain-targeted nanocarrier delivery systems, showcasing their potential in administering water-soluble anti-infection drugs for intracranial infection treatments, and suggesting promising avenues for clinical translation.Graphical abstract

Formulation and Evaluation of Idebenone Microemulsion as a Potential Approach for the Transmucosal Drug Delivery Systems

Idebenone, a synthetic analogue of ubiquinone (Co-Q10), is used for the treatment of Leiber’s hereditary optic neuropathy. Although it is almost completely absorbed from GIT, its extensive rate of metabolism makes its oral bioavailability less than 1%. This study aims to formulate the poorly water-soluble drug as nanoemulsion (NE) to increase drug solubility as well as transmucosal permeation and circumventing hepatic biodegradation by using transmucosal routes of administration such as intranasal rout to enhance drug bioavailability. Nanoemulsion components were selected through screening of the preferential solubility of IDB in several oils and emulsifying agents and subsequent formulation optimization through screening for their best miscibility through phase study. Lemongrass oil showed superior characteristics to represent the oil phase in which the drug was dissolved while Cremophor EL® and Transcutol-P® represented the surfactant system. The method of spontaneous-emulsification was used to prepare twelve NE formulas (F1-F12) which were subjected to several characterization tests. Out of four successful formulas, F-11 showed the best globule size (45.6nm), PDI (0.19) zeta-potential (-2.8 mV), low viscosity and suitable pH (5.9). Using sheep nasal mucosa as model, (F-11) was subjected to ex-vivo transmucosal permeation study against plain drug oil dispersion with pronounced enhanced permeation due to formulation as NEs. Permeation kinetic parameters were obtained such as permeation rate 40.9 µg/h/cm2, lag time 15min, permeability coefficient 40.9x10-4 cm/h and enhancement ratio 39. The outcome of this study indicates the possibility of incorporation of this formula into a suitable carrier for finalizing its formulation as non-enteral dosage form with enhanced IDB bioavailability.

Development of a simple paste for 3D printing of drug formulations containing a mesoporous material loaded with a poorly water-soluble drug

Poorly soluble drugs represent a substantial portion of emerging drug candidates, posing significant challenges for pharmaceutical formulators. One promising method to enhance the drug’s dissolution rate and, consequently, bioavailability involves transforming them into an amorphous state within mesoporous materials. These materials can then be seamlessly integrated into personalized drug formulations using Additive Manufacturing (AM) techniques, most commonly via Fused Deposition Modeling. Another innovative approach within the realm of AM for mesoporous material-based formulations is semi-solid extrusion (SSE). This study showcases the feasibility of a straightforward yet groundbreaking hybrid 3D printing system employing SSE to incorporate drug-loaded mesoporous magnesium carbonate (MMC) into two different drug formulations, each designed for distinct administration routes. MMC was loaded with the poorly water-soluble drug ibuprofen via a solvent evaporation method and mixed with PEG 400 as a binder and lubricant, facilitating subsequent SSE. The formulation is non-aqueous, unlike most pastes which are used for SSE, and thus is beneficial for the incorporation of poorly water-soluble drugs. The 3D printing process yielded tablets for oral administration and suppositories for rectal administration, which were then analyzed for their dissolution behavior in biorelevant media. These investigations revealed enhancements in the dissolution kinetics of the amorphous drug-loaded MMC formulations. Furthermore, an impressive drug loading of 15.3 % w/w of the total formulation was achieved, marking the highest reported loading for SSE formulations incorporating mesoporous materials to stabilize drugs in their amorphous state by a wide margin. This simple formulation containing PEG 400 also showed advantages over other aqueous formulations for SSE in that the formulations did not exhibit weight loss or changes in size or form during the curing process post-printing. These results underscore the substantial potential of this innovative hybrid 3D printing system for the development of drug dosage forms, particularly for improving the release profile of poorly water-soluble drugs.

Impact of Grinding Balls on the Size Reduction of Aprepitant in Wet Ball Milling Procedure

One of the widely used approaches for improving the dissolution of poorly water-soluble drugs is particle size reduction. Ball milling is a mechanical, top-down technique used to reduce particle size. The effect of ball number, ball size and milling speed on the properties of milled Aprepitant is evaluated. A full factorial design was employed to investigate the influence of affecting factors on particle size reduction. The initial suspension was made by suspending the drug in distilled water using excipients followed by milling in a planetary ball mill. Ball size, ball number and milling speed modulated particle size distribution of Aprepitant. Increasing the number of balls from minimum to maximum for each ball size led to approximately a 28% reduction in mean particle size, a 37% decrease in D90%, and a 25% decrease in the ratio of volume mean particle diameter to numeric mean particle diameter. On average, using 10 mm balls instead of 30 mm balls reduced mean particle size by 1.689 µm. As a result, ball size, ball number, and milling speed are three effective factors in the process of ball milling. By increasing the ball number and decreasing the ball size, efficient micronization of drug particles takes place and the particle size is more uniform.

Characterizing interregional differences in the rheological properties and composition of rat small intestinal mucus.

The mucus layer in the small intestine is generally regarded as a barrier to drug absorption. However, the mucus layer is a complex system, and presently, only a few studies have been conducted to elucidate its physicochemical properties. The current study hypothesizes that the mucus layer contains solubility-enhancing surfactants and thus might aid the oral absorption of poorly water-soluble drugs.Mucus was sampled from sections of the small intestine of fasted rats to analyze the rheological properties and determine the mucus pH and concentrations of proteins and endogenous surfactants, i.e., bile salts, polar lipids, and neutral lipids.The mucus layer in the two proximal sections of the small intestine exhibited different rheological properties such as higher zero-shear viscosity and lower loss tangent and higher protein concentrations compared to all subsequent sections of the small intestine. The pH of the mucus layer was stable at ~ 6.5 throughout most of the small intestine, but increased to 7.5 in the ileum.The bile salt concentrations increased from the duodenum (16.0 ± 2.2mM) until the mid jejunum (55.1 ± 9.5mM), whereas the concentrations of polar lipids and neutral lipids decreased from the duodenum (17.4 ± 2.2mM and 37.8 ± 1.6mM, respectively) until the ileum (4.8 ± 0.4mM and 10.7 ± 1.1mM, respectively).In conclusion, the mucus layer of the rat small intestine contains endogenous surfactants at levels that might benefit solubilization and absorption of orally administered poorly water-soluble drugs.

African Breadfruit Seed Oil as Lipid Phase of Self-Emulsifying Drug Delivery System for Improved Gastrointestinal Fluid Solubility of Ibuprofen: Design and Evaluation

Introduction: Rain forest vegetations all over the world produce large quantity of economically important seed oils which, in most developing countries are utilized only as food condiments but hardly employed in pharmaceutical formulations.&#x0D; Objectives: The purpose of this work was to formulate ibuprofen-loaded self-emulsifying drug delivery system for the enhancement of the gastrointestinal fluid solubility of this poorly water soluble drug.&#x0D; Methods: The breadfruit seed oil was extracted by the soxhlet extraction technique and characterized for various physicochemical properties including acid, iodine, peroxide, saponification values and organoleptic properties.  The super saturation solubility process, water titration studies and pseudo ternary phase diagrams were used to select and quantify the components of the emulsion systems. The liquid self-emulsifying drug delivery systems were converted to solid forms by adsorption onto a blend of miceocrystalline cellulose and Aerosil-200 powders. The resulting wet mass was dried and processed for encapsulation.&#x0D; Results: The percentage yield of the oil from the extraction process was 20.68 % while the acid, iodine, and saponification values were, 4.12 ± 1.24, 21.91 ± 0.88, and 302.45 ± 1.22 respectively. The ibuprofen exhibited higher solubility in the hydrolysed oil than in the crude form. Fourier transform infrared analysis did not reveal existence of component incompatibility. The optimized liquid and solid emulsions exhibited standard characteristics that were compatible to previous literature reports. The formulations also exhibited superior drug release properties over two control samples.&#x0D; Conclusion: It was concluded that Breadfruit seed oil has the potential to function as the lipid component of ibuprofen-loaded self-emulsifying drug delivery system formulated to enhance the aqueous solubility of the drug.

Abstract 6745: Crafting hyaluronic acid-based nanoparticles for enhanced LN targeting as a potent priming tool in immunotherapy

Abstract Background: Cholesterol-conjugated hyaluronic acid, synthesized by grafting cholesterol moieties onto hyaluronic acid, spontaneously formed nano-sized hydrogel of approximately 30-100nm in water. This hyaluronic acid derivative (HA nanogel) has demonstrated the ability to encapsulate various modalities, including low- and medium-sized molecules, peptides, and proteins. Previous reports have highlighted its efficacy in solubilizing poorly water-soluble drugs and serving as a sustained-release matrix. In this study, we explore the potential of HA nanogels encapsulating antigen peptides with adjuvant as a cancer vaccine and a priming tool for combinational immunotherapy. Method: We prepared HA nanogels as a novel peptide carrier for cancer vaccines and attempted to encapsulate various peptides, including neoantigen (mERK2) peptides expressed in immune checkpoint inhibitor (ICI) therapy-resistant fibrosarcoma cell line CMS5a, gp-100 peptides expressed in metastatic melanoma cell line B16F10, and MAGEA4. Our experiments covered APC uptake, antigen-specific CTL induction, and anti-tumor studies to demonstrate the utility of HA nanogels in these applications. Results: HA nanogel efficiently formed stable complexes with mERK2, gp-100 and MAGEA4 long peptides, each with diameters of 30-100nm. The facile and simple vaccine formulation processes with HA nanogel achieved high drug content and high encapsulation efficiency of 90% or higher. Fluorescently labeled mERK2 long peptide encapsulated in HA nanogel vaccines were subcutaneously administered to BALB/c mice, and uptake analysis of mERK2 long peptides in draining lymph nodes (dLN) was performed using flow cytometry. In comparison to the group receiving mERK2 long peptide without nanogel encapsulation, the HA nanogel group exhibited higher uptake by macrophages and dendritic cells in the dLN. Administering HA nanogel vaccines containing mERK2 long peptides with CpG oligoDNA resulted in higher antigen-specific CD8+ T cells compared to the group receiving mERK2 long peptides without encapsulation. Strong anti-tumor effects were demonstrated in mice models with subcutaneously transplanted CMS5a and B16F10 cell lines. The enhanced efficacy through co-administration with ICI was also confirmed. Conclusion: HA nanogel vaccines efficiently deliver antigen peptides to macrophages and dendritic cells, inducing antigen-specific CTL responses, thereby demonstrating anti-tumor effects against cold tumors such as CMS5a and B16F10. HA nanogels have the potential not only as carriers for cancer vaccines but also as priming tools for combinational immunotherapy. Citation Format: Takashi Nakai, Fumiyasu Momose, Kohei Yabuuchi, Makiko Yamane, Tae Hayashi, Linan Wang, Yoshiyuki Nakagawa, Shogo Aso, Toru Katsumata, Tsuyoshi Shimoboji, Yoshihiro Miyahara. Crafting hyaluronic acid-based nanoparticles for enhanced LN targeting as a potent priming tool in immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6745.

Solubility of Poorly Soluble Drugs in Phosphatidylcholine-Based Drug Delivery Systems: Comparison of the Loading Capacity in the Bulk Formulation and Its Dispersed State.

The aim of this study was to determine the drug loading capacity of phosphatidylcholine-based formulations for four poorly water-soluble drug substances (clofazimine, fenofibrate, artemether, cannabidiol). Two self-dispersing lipid formulations were investigated, which consisted of soybean phospholipids, medium-chain triglycerides and ethanol with a different phospholipid-oil ratio. The direct loading of the bulk formulation was conducted with dual centrifugation, which proved to be a suitable method for screening experiments with the highly viscous formulations. To estimate possible precipitation after dispersion in the gastrointestinal fluids, the solubility of the drugs was investigated in the dispersed formulations. For this purpose, nanodispersions were prepared from the bulk formulations via high pressure homogenization and subsequently subjected to passive loading. A newly developed HPLC method with Charged Aerosol Detection allowed a simultaneous evaluation of the content of soybean lecithin and medium-chain triglycerides in the nanodispersions. When comparing the two phosphatidylcholine-based formulations, a high content of oil was advantageous with regard to a high loading capacity. Drug substances with melting points below 150 °C exhibited a high solubility in the phospholipid-based formulations. A surprisingly high solubility was observed for artemether and cannabidiol with up to 13.0% and 33.3% drug loaded to the formulations, respectively. In the dispersions, a similar solubility as in the bulk formulations was obtained for fenofibrate and cannabidiol. Clofazimine yielded a higher loading result in the nanodispersions than in the bulk formulation.