Bone metastasis remains a clinical challenge and is still considered incurable. While nanoparticles-based drug delivery and photothermal therapy (PTT) show promise in treating subcutaneous solid tumor, their therapeutic outcome in treating bone metastasis is limited, due to the inaccessibility of bone metastatic site and the complexity of bone metastasis. Herein, we reported a simple nanoplatform composed of thermo-sensitive liposomes (TSL) and gold nanorods (GNR) to treat bone metastasis through improved chemotherapy combined with GNR-assisted PTT. Lipid combination of TSL was firstly tailored to regulate its stability under physiological condition as well as its sensitivity in responding to PTT-caused mild hyperthermia. The obtained TSL with loaded drug was then combined with GNR to form the nanoplatform through unsophisticated incubation. Cell experiments revealed that upon near-infrared (NIR) irradiation, the nanoplatform effectively inhibited the viability and migration ability of tumor cells through PTT, PTT-triggered thermo-sensitive drug release, and PTT-augmented sensitivity of tumor cells to drug. In a murine model of bone metastasis, the nanoplatform enabled effective delivery of loaded drug and GNR to bone metastatic site for rapid drug release upon local NIR irradiation. Through killing tumor cells and rebalancing the turnover of osteoclasts and osteoblasts, the nanoplatform largely preserved bone structure for pain relief and survival extension. Inspired by the simplicity of nanoplatform acquirement and treatment operation, the strategy of liposomes-based thermo-sensitive drug delivery in combination with GNR-assisted PTT is considered greatly promising in treating bone metastasis.

RCC is a malignant tumor arising from the urothelium of renal parenchyma that remains challenging to be treated. In this study, we assessed the anti-tumor effects of Resveratrol liposomes (RES-lips) combined with sorafenib on renal cell carcinoma (RCC) and explored the potential mechanisms underlying the improvement of sorafenib resistance models. Tumor growth and survival following treatment with sorafenib alone or in combination with RES-lips was evaluated in a RCC xenograft mouse model. Flow cytometry results demonstrated that the combination of RES-lips and sorafenib significantly enhanced the G1/S phase arrest of sorafenib-resistant cells. When compared with the PBS or monotherapy groups, treatment with RES-lips combined with sorafenib exhibited significant inhibition of tumor growth in the RCC xenograft mouse model with tumor growth inhibition (TGI) rates and complete remission (CR) rates of 90.1 % and 50 %, respectively. Concersely, the maximum TGI rate was 53.6 % in the RES-lips monoherapy group and 29.2 % and in the sorafenib monotherapy group, and no animals achieved CR. Additionally, the current combination therapy promoted the proliferation of unactivated splenic lymphocytes and the proliferation of soybean protein A- and lipopolysaccharide-stimulated lymphocytes compared with PBS or monotherapy treatments. Further western blotting analysis suggested that RES-lips may enhance the resistance of RCC to sorafenib by inhibiting PI3K-AKT-mTOR and VHL-HIF signaling pathways, ultimately augmenting the tumor growth inhibition effect of the combination therapy. RES-lips may improve the sorafenib resistance in RCC, and the underlying mechanism may be related to the regulation of PI3K-AKT-mTOR and VHL-HIF signaling pathways.

Nucleic acid-based therapeutics are a common approach that is increasingly popular for a wide spectrum of diseases. Lipid nanoparticles (LNPs) are promising delivery carriers that provide RNA stability, with strong transfection efficiency, favorable and tailorable pharmacokinetics, limited toxicity, and established translatability. In this review article, we describe the lipid-based delivery systems, focusing on lipid nanoparticles, the need of their use, provide a comprehensive analysis of each component, and highlight the advantages and disadvantages of the existing manufacturing processes. We further summarize the ongoing and completed clinical trials utilizing LNPs, indicating important aspects/questions worth of investigation, and analyze the future perspectives of this significant and promising therapeutic approach.

Cancer is the leading cause of death globally, and conventional treatments have limited efficacy with severe side effects. The use of nanotechnology has the potential to reduce the side effects of drugs by creating efficient and controlled anticancer drug delivery systems. Nanoparticles (NPs) used as drug carriers offer several advantages, including enhanced drug protection, biodistribution, selectivity and, pharmacokinetics. Therefore, this review is devoted to various organic (lipid, polymeric) as well as inorganic nanoparticles based on different building units and providing a wide range of potent anticancer drug delivery systems. Within these nanoparticulate systems, chitosan (CS)-based NPs are discussed with particular emphasis due to the unique properties of CS and its derivatives including non-toxicity, biodegradability, mucoadhesivity, and tunable physico-chemical as well as biological properties allowing their alteration to specifically target cancer cells. In the context of streamlining the nanoparticulate drug delivery systems (DDS), innovative nanoplatform-based cancer therapy pathways involving passive and active targeting as well as stimuli-responsive DDS enhancing overall orthogonality of developed NP-DDS towards the target are included. The most up-to-date information on delivering anti-cancer drugs using modern dosage forms based on various nanoparticulate systems and, specifically, CSNPs, are summarised and evaluated concerning their benefits, limitations, and advanced applications.

Radiofrequency catheter ablation (RFCA) is the preferred technique for the treatment of atrial fibrillation, but the recovery of electrical conduction after ablation seriously endangers the health of patients. This study aimed to develop reactive oxygen species (ROS) responsive double-locked liposome collaborative photodynamic therapy (PDT) to target the ablation area and reduce the recovery of electrical conduction after ablation. The successful synthesis of β-cyclodextrin modified with phenylboronic acid pinacol ester (OCD) was confirmed by H NMR and FT-IR. Furthermore, the successful synthesis of octadecylamine-modified indocyanine green (ICG-ODA) was confirmed by H NMR and mass spectrometry. The ICG-ODA was encapsulated in liposomes to generate a double-locked hybrid liposome (ICG-ODA@rNP), which was subsequently characterized. Several properties of ICG-ODA@rNP were evaluated, including the drug release, targeting ability and ability to inhibit electrical conduction recurrence. Moreover, a model was constructed for the blockage of electrical conduction after RFCA in rabbits to further evaluate ICG-ODA@rNP. The preliminary safety evaluation of ICG-ODA@rNP was also performed. The ICG-ODA@rNP with a uniform particle size showed excellent storage stability. The nanoparticle can sensitively release drugs under ROS environment, and exhibits excellent photothermal effects. Furthermore, ICG-ODA@rNP can circulate for a long time and accumulate significantly in the ablation area. In a pacing test with a left atrial appendage (LAA), these nanoparticles, combined with PDT, reduced the ratio of electrical conduction recovery, which was confirmed by a hematoxylin and eosin (H&E) test. Further molecular analysis revealed that ICG-ODA@rNP could increase RFCA-induced apoptosis and ROS levels. Specifically, ICG-ODA@rNP significantly increased the expression of Bax and cleaved caspase-3, and decreased the expression of Bcl-2. In addition, the excellent biosafety of the double-locked nanoparticle was verified. This study provides evidence that ICG-ODA@rNP, with the double lock characteristic and biosafety, which exhibits a targeting effect on RFCA-induced cardiac injury areas, which further reduce electrical conduction recovery in RFCA areas by collaborativing PDT.

An innovative nanovehicle based on lipid nanocapsules (LNC) was designed to facilitate the passage of a new 5-HT receptor antagonist, namely PUC-10, through the blood-brain barrier. PUC-10 is a new synthetic -arylsulfonylindole that has demonstrated potent 5-HT receptor antagonist activity, but it exhibits poor solubility in water, which indicates limited absorption. The lipid nanocapsules designed had a nanometric size (53 nm), a monomodal distribution (PI<0.2), a negative Z potential (-17 ± 7 mV) and allowed efficient PUC-10 encapsulation (74 %). Furthermore, the LNC demonstrated to be stable for at least 4 weeks at 4 °C (storage conditions), for at least 4 h in DMEM at pH 7.4, and for 18 h in water with 5 % DMSO, with both latter conditions maintained at 37 °C. They also demonstrated that cell viability was not affected at the different concentrations studied. Finally, studies that simulate the blood brain barrier (PAMPA-BBB) demonstrated that the nanoencapsulation of PUC-10 promoted their penetration through the blood-brain barrier, with a calculated permeability of 1.3 × 10 cm/s, compared to the null permeability exhibited by non-nanoencapsulated PUC-10.

Exudate absorption is a key parameter for proper wound dressing performance. Unlike standardized tests that consider exudate viscosity close to that of water, patients' exudates vary greatly in composition and, therefore, viscosity. This work aimed to investigate the effects of exudate viscosity and pore size of hydrogel-like dressings on the exudate absorption rate to establish rational criteria for the design of dressings that can meet the personalized needs of wound treatment. Computer-aided design (CAD) was used for Digital Light Processing (DLP) 3D printing of hydrogels with 0%, 30% and 60% porosity. The hydrogels were characterized in detail, and the absorption of two simulated exudate fluids (SEFs) was video-recorded. The same CAD files were used to develop models to simulate exudate uptake rate. Both data and modeling revealed that low-viscosity SEF penetrates faster through relatively small hydrogel pores (approx. 400 μm) compared to larger pores (approx. 1100 μm) due to capillary forces. However, vertical uptake took longer than when simulated using CAD design due to lateral fluid absorption through the pore walls in the hydrogel bulk. Distortions of hydrogel channels (micro-CT images) and lateral fluid absorption should be both considered for simulation of SEF penetration. Overall, the results evidenced that porous hydrogel dressings allow rapid penetration (within a few seconds) and hosting of exudates, especially for pore size <1 mm. This information may be useful for design criteria of wound dressings with adequate fluid handling and drug release rate.

Autologous vein grafts have attracted widespread attention for their high transplantation success rate and low risk of immune rejection. However, this technique is limited by the postoperative neointimal hyperplasia, recurrent stenosis and vein graft occlusion. Hence, we propose the platelet membrane-coated Poly(lactic--glycolic acid) (PLGA) containing sildenafil (PPS). Platelet membrane (PM) is characterised by actively targeting damaged blood vessels. The PPS can effectively target the vein grafts and then slowly release sildenafil to treat intimal hyperplasia in the vein grafts, thereby preventing the progression of vein graft restenosis. PPS effectively inhibits the proliferation and migration of vascular smooth muscle cell (VSMCs) and promotes the migration and vascularisation of human umbilical vein endothelial cells (HUVECs). In a New Zealand rabbit model of intimal hyperplasia in vein grafts, the PPS significantly suppressed vascular stenosis and intimal hyperplasia at 14 and 28 days after surgery. Thus, PPS represents a nanomedicine with therapeutic potential for treating intimal hyperplasia of vein grafts.

Many researchers have studied the oral absorption mechanisms yet, however, considering stabilizers often participate in the absorption process of nanocrystals, these known mechanisms may be incorrect. Hence in this study, we aimed to explore the correct absorption mechanism of nanocrystals by performing related studies on stabilizer-free nanocrystals. We firstly prepared stabilizer-free silymarin nanocrystals by high-pressure homogenization, and then performed absorption-related studies, such as solubility, dissolution rate, pharmacokinetic study, cellular uptake and intracellular transport. Results showed the stabilizer-free silymarin nanocrystals had an average particle size of (450.2 ± 4.46) nm, with PDI of 0.280 ± 0.021 and Zeta potential of -26.9 ± 2.4 mV. The conversion of silymarin crude drug to stabilizer-free silymarin nanocrystals increased the compound's solubility by 1.41 times, with a dissolution rate of 92.2 % in water within 30 min compared to 38.5 % for crude drugs. Pharmacokinetic studies showed the oral bioavailability of stabilizer-free silymarin nanocrystals was found to be 1.48 times greater than that of the crude drugs. The cell experimentation results demonstrated that the stabilizer-silymarin nanocrystals can improve uptake but have poor transmembrane transport properties. Most researchers believe that nanocrystals can enhance transmembrane transport of drugs via an endocytosis-mediated pathway. In fact, nanocrystals are indeed endocytosed more by the cells, but this transport pathway is poor because the cells lack the intracellular transport pathway to transport nanocrystals from the AP side to the BP side. Therefore, we believe that the intracellular transport of nanocrystals can be enhanced by modifications and other carriers if needed to improve nanocrystals' ability to promote oral absorption.

Chronic wound infections are attributed to delayed tissue repair, which remains a major clinical challenge in long-term health care. Particularly, infections with antibiotic resistance have more serious effects on health, often resulting in unsuccessful treatments. Thus, antimicrobial peptide (AMP)-based therapy holds promise as a potential therapeutic approach to overcoming drug resistance. Conventional wound dressing is a passive strategy for wound care that is not capable of eradicating pathogens and promoting tissue repair. In this study, we aim to construct an advanced wound dressing; a thermo-responsive hydrogel incorporated with lactoferricin (Lfcin) niosome (Lfcin-Nio/hydrogel) for bacterial pathogen treatment. The Lfcin-loaded niosome (Lfcin-Nio) has a particle size of 396.91 ± 20.96 nm, 0.38 ± 0.01 of PdI, -10.5 ± 0.3 mV of ζ potential, and 72.30 ± 7.05 % Lfcin entrapment efficiency. Lfcin-Nio exhibited broad antibacterial activity on both drug-susceptible and drug-resistant strains, and also on bacteria residing in the biofilm matrix. The Lfcin-Nio/hydrogel was fabricated from 0.5 % / poloxamer 188-20 % w/v poloxamer 407, and supplemented with Lfcin-Nio and epidermal growth factor (EGF). The physical properties of Lfcin-Nio/hydrogels showed elasticity, swelling ability, and strong injectability with responsiveness to 33-37 °C temperatures. The biological properties of Lfcin-Nio/hydrogels exhibited a bactericidal effect against drug-resistant strains of and and showed less toxicity to the human skin fibroblast. It also promoted the healing of scratches by 55 % within 6 h, compared to the wound closure rate of 20 % in the cell control. The inflammatory response of the Lfcin-Nio/hydrogel-treated cells was reduced suppression of and mRNA expressions. From this study, Lfcin-Nio/hydrogels can be suggested as a modern wound dressing that possesses multifunctional and beneficial properties for the management of chronic wound infections.

This study aimed to formulate and statistically optimize spanlastics loaded spongy insert (SPLs-SI) of prednisolone Na phosphate (PRED) to enhance and sustain its anti-inflammatory effect in a controlled manner. An I-optimal optimization was employed using Design-Expert® software. The formulation variables were sonication time, the Span 60: EA ratio and type of edge activator (Tween 80 or PVA) while Entrapment efficiency (EE%), Vesicles' size (VS) and Zeta potential (ZP) were set as the dependent responses. This resulted in an optimum spanlastics (SPLs) formulation with a desirability of 0.919. It had a Span60:Tween80 ratio of 6:1 with a sonication time of 9.5 min. It was evaluated in terms of its EE%, VS, ZP, release behavior in comparison to drug solution in addition to the effect of aging on its characteristics. It had EE% of 87.56, VS of 152.2 nm and ZP of -37.38 Mv. It showed sustained release behavior of PRED in comparison to drug solution with good stability for thirty days. TEM images of the optimized PRED SPLs formulation showed spherical non-aggregated nanovesicles. Then it was loaded into chitosan spongy insert and evaluated in terms of its visual appearance, pH and mucoadhesion properties. It showed good mucoadhesive properties and pH in the safe ocular region. The FTIR, DSC and XRD spectra showed that PRED was successfully entrapped inside the SPLs vesicles. It was then exposed to an in-vivo studies where it was capable of enhancing the anti-inflammatory effect of PRED in a sustained manner with once daily application compared to commercial PRED solution. The spongy insert has the potential to be a promising carrier for the ocular delivery of PRED.

Cancer-associated fibroblasts (CAFs) are abundant stromal cells residing in a tumor microenvironment (TME) which are associated with the progression of tumor. Herein, we developed novel CAFs-targeting polymeric nanoparticles encapsulating a synthetic 8--methylfusarubin (OMF) compound (OMF@NPs-anti-FAP). Anti-FAP/fibroblast activation protein antibody was employed as a CAFs-targeting ligand. The physicochemical properties of the synthesized nanomaterials were firstly investigated with various techniques. The cytocompatibility of polymeric nanoparticles (NPs) was elicited through cell viability of CAFs and human breast epithelial cells, MCF-10A. Additionally, the anti-FAP-conjugated NPs displayed different degrees of cellular internalization regarding the FAP expression level on the CAFs' surface. However, CAFs exposed to NPs containing OMF demonstrated significant cell death which were associated with the apoptotic pathway as confirmed by caspase-3/7 activity. Upon OMF@NPs-anti-FAP treatment, an enhanced toxicity was clearly observed in 3D spheroid models. High FAP-expressed PC-B-132CAFs demonstrated a high percentage of cell death compared to other cells with a low level of FAP expression analyzed by flow cytometry (e.g. MCF-10A, HDFa, and PC-B-142CAFs). This result emphasized the importance of anti-FAP antibody as a targeting ligand. These findings suggest that the fabricated nanosystem of OMF-loaded polymeric NPs with CAFs' high specificity holds a potential NP-based platform for improvement in breast cancer treatment.

In the current study, voriconazole (VCZ) augmented glycerosomes were optimized for topical otomycosis management according to a 2 factorial design, employing a thin film hydration method. By optimizing Glycerol volume, limonene: VCZ ratio and Span® 60: soybean phosphatidyl choline (PC) ratio, glycerosomes with maximum percentage entrapment efficiency (%EE) and zeta potential (ZP) and minimum vesicle size (VS) and polydispersity index (PDI) were to be obtained. An optimal augmented glycerosomal formula (OAG) that contained 10 mg VCZ, 150 mg PC, and 3 mL glycerol, comprising 2.5: and 0.92:1 ratios of the latter two independent variables, was proposed via numerical optimization. OAG exhibited high %EE and ZP values and acceptable low values for VS and PDI (84.3 ± 2.0 %, -38.8 ± 1.8 mV, 191.0 ± 1.1 nm, and 0.192 ± 0.01, respectively). Extensive in testing of OAG revealed the entrapment of VCZ within OAG, biphasic in release profile, stability for up to 3 months at 2-8 °C and spherical morphology of OAG with VS like that obtained via zetasizer. OAG demonstrated higher permeated amounts of VCZ and flux values than VCZ suspension, leading to an enhancement ratio of 2.56 in the permeation study. The deeper penetration ability of OAG demonstrated by Confocal Laser Scanning Microscopy and its superior in antifungal activity confirmed the validity of the study. Also, the histopathological study confirmed the safety of OAG for topical use, suggesting that VCZ OAG was a promising topical antimycotic formula.

The study explored stearylamine containing cationic elastic liposomes to improve topical delivery and efficacy of ketoconazole (KETO) to treat deeply seated fungal infections. Stearylamine was used for dual functionalities (electrostatic interaction and flexibility in lipid bilayer). Hansen solubility program (HSPiP) estimated Hansen solubility parameters (HSP) based on the SMILE file and structural properties followed by experimental solubility study to validate the predicted values. Various formulations were developed by varying phosphatidylcholine and surfactants (tween 80 and span 80) concentration. To impart cationic properties, stearylamine (1.0 %) was added into the organic phase. Using quality by design (QbD) method, we optimized the formulations and evaluated for vesicle size, polydispersity index, zeta potential, morphology (scanning electron microscopy), in vitro drug release (%), and ex vivo permeation profiles. Result showed that there is a good correlation (0.65) between HSPiP predicted and actual experimental solubility of KETO in water, chloroform, S80, and tween 80. Spherical OKEL1 showed an established correlation between the predicted and the actual formulation parameters (size, zeta potential, and polydispersity index) (259 nm vs 270 nm, +2.4 vs 0.21 mV, and 0.24 vs 0.27). OKEL1 was associated with the highest value of %EE (83.1 %) as compared to liposomes. Finally, OKEL1 exhibited the highest % cumulative permeation (49.9 %) as compared to DS (13 %) and liposomes (25 %). Moreover, OKEL1 resulted in 4-fold increase in permeation flux as compared to DS which may be attributed to vesicular mediated improved permeation and gel based compensated trans epidermal water loss in the skin. The drug deposition elicited OKEL1 and OKEL1-gel as suitable carriers for maximum therapeutic benefit to treat deeply seated fungal infections.

Nanotechnology has attracted extensive attention in the diagnosis and treatment of cancer. Therefore, the research aimed at developing new nanomaterials and exploring their applications in biomedicine has attracted more attention. In this study, BiS-Au nanoclusters (BiS-AuNCs) as fluorescence/infrared thermal imaging-guided photothermal therapy (PTT) was prepared for the first time. It was achieved in a facile and mild way by optimizing the amount of Bi and Au using bovine serum albumin (BSA) as reducer and stabilizer. The as-prepared BiS-AuNCs with special morphology showed high stability, excellent biocompatibility and good photostability. Apart from these, it also can accumulate at tumor sites and exhibit considerable fluorescence/infrared thermal imaging-guided PTT. BiS-AuNCs nanoparticles integrate imaging and therapeutic functions into an advanced application platform, which provides the possibility to build a novel nano-cancer diagnosis and treatment platform.

Pharmacies are currently unable to stock proper oral dosage forms for pediatric populations. This leads to manipulation of medications or the need to compound specialized medications, which can be a time-consuming process. Using Semisolid Extrusion (SSE) additive manufacturing (AM), specialized medications can be produced in an expedited process from off-the shelf medication in a hospital or outpatient pharmacy setting. In this study, tablets with a desired dose of 5 mg of metoprolol tartrate derived from commercial Seloken™ 50 mg tablets were 3D printed in a hospital setting. Validation testing was done on five batches, highlighting tablets with a high uniformity in mass and dimension, drug content, acceptable microbial assays, and prolonged release during in-vitro analysis. The average drug content found for the tablets was within ±6% of 5 mg for all batches produced. Comparisons were done between the SSE tablets and capsules produced in an external compounding facility, highlighting several positive aspects of SSE-produced tablets beyond simply shortening the production timeline. The SSE tablets printed in this study are characterized by their smaller size, enhanced prolonged release properties, and more uniform drug content across the tested samples. Additionally, interviews with pharmaceutical professionals were conducted to determine the positive aspects of SSE and further improvements to bring this technique as seamlessly as possible into the pharmacy. This study underscores the feasibility of employing SSE in the production of specialized medications within a hospital environment. Furthermore, it highlights the methodological advantages SSE offers over existing production standards, demonstrating its potential to improve pharmaceutical manufacturing in healthcare settings.

Tacrolimus, a potent immunosuppressant, is widely used in several formulations to treat organ rejection in transplant patients. However, its physicochemical stability poses significant challenges, including thermal instability, photostability issues, low solubility, and drug-excipient incompatibility. This review article focuses on the details of these challenges and discusses the analytical methods employed to study tacrolimus stability, such as thermal, spectroscopic, and chromatographic methods in different formulations. New formulations to enhance tacrolimus stability are explored, including lipid-based nanocarriers, polymers, and thin film freezing. Researchers and formulators can optimize tacrolimus formulations to improve efficacy and patient outcomes by understanding and addressing these stability challenges.

Cervical cancer is a leading cause of cancer-related mortality in females worldwide, necessitating urgent solutions for effective treatment. Paclitaxel (PTX), a natural diterpene alkaloid compound, has the ability to inhibit mitosis and induce programmed apoptosis in tumor cells. However, its toxicity and drug resistance limit its efficacy in certain cervical cancer patients. β-elemene (β-ELE) can reverse multidrug resistance by inhibiting ATP-binding cassette transporters, thereby enhancing chemotherapy drug retention. Therefore, we propose a combination therapy using PTX/β-ELE to improve chemotherapy sensitivity. To enhance targeted drug delivery, we developed M1-macrophage-membrane-coated nanoparticles (M1@PLGA/PTX/β-ELE) for co-delivery of PTX&β-ELE. Through both and cervical cancer models, we demonstrated that M1@PLGA/PTX/β-ELE effectively suppressed tumor progression and polarization of tumor-associated macrophages. Furthermore, H&E staining confirmed the high therapeutic biosafety of M1@PLGA/PTX/β-ELE as there was no significant damage observed in major organs throughout the entire therapeutic process. Overall, this study presents a targeted biomimetic nanoplatform and combinatorial strategy that synergistically enhances chemosensitivity in malignant tumors.

Pain produces several physiological, and degenerative complications. This study aimed to formulate meloxicam (MLX) in liposomes to increase solubility and deliver MLX in a controlled manner to overcome its poor aqueous solubility and relatively short t problems. Liposomes were prepared by thin film hydration followed by ultrasonication. Tests for characterizing formulations included particle size, span, entrapment efficiency, drug loading, stability, differential scanning calorimetry (DSC), Fourier transformation infrared (FT-IR) spectroscopy, morphology, release, release kinetics mathematical modeling, and an pain model in dogs undergoing orthopedic surgeries, followed by pharmacokinetics, pharmacodynamics, and pain assessment studies in comparison to the reference standard, Mobitil®. Liposomal MLX had a particle size of around 100 nm, 82 % entrapment efficiency, and 4.62 % drug loading. Stability studies, DSC, and FT-IR spectroscopy indicated that liposomes were highly stable. The formulation showed an improved controlled release pattern and an enhanced pharmacokinetic behavior as manifested by higher t and AUC and lower Cl/F in comparison to Mobitil®. The pharmacodynamics study and pain scales demonstrated liposomal MLX managed postoperative pain better than Mobitil®. In conclusion, the incorporation of MLX in liposomes increased its solubility and stability, as well as its pain management properties.

Mulberry Diels-Alder-type adducts (MDAAs), isolated from root bark, exhibit dual activity against viral and bacterial pathogens but show sobering efficacy following oral administration. Inhalation administration may overcome issues with oral bioavailability and improve efficacy for the treatment of respiratory infections. To assess the suitability of MDAAs for inhalation administration, physicochemical (e.g. pH, pK, logP, pH-dependent solubility) and biopharmaceutical (epithelial cytotoxicity, permeability, and uptake) properties of two bioactive MDAA stereoisomers sanggenon C (SGC) and sanggenon D (SGD) were evaluated as isolated natural compounds and within parent extracts (MA21, MA60). Despite their structural similarity, SGD exhibited a 10-fold higher solubility than SGC across pH 1.2-7.4, with slight increases at neutral pH. Both compounds were more soluble in isolated form than in the parent extracts. The more lipophilic SGC was found to be more cytotoxic when compared to SGD, indicating a better cellular penetration, which was confirmed by uptake studies. Nonetheless, SGC and SGD exhibited no measurable permeability across intact Calu-3 monolayers, highlighting their potential for increased lung retention and improved local anti-infective activity following inhalation administration. Results suggest that SGC and SGD in isolated form, rather than as extracts, are promising candidates for pulmonary drug delivery to treat lung infections.

MUPS (multiple unit particle systems) are oral dosage forms consisting of small particles which are filled into capsules or compressed into tablets. Compared to monolithic sustained-release tablets, MUPS tablets rapidly disintegrate inside the stomach releasing the contained small particles, which can be emptied from the stomach independent of housekeeping waves. Control of release can be achieved by adapting the particle composition. Despite the advantages of MUPS, only a limited number of preparations are available on the market. 3D printing could be a new advantageous method to produce MUPS tablets compared to the conventional production via tableting. Due to the increasing research interest in personalised medicine, especially regarding dose adjustments, this flexible production approach could be a promising concept. Therefore, this work proposes a concept for printing MUPS tablets using a dual extrusion fused filament fabrication 3D printer. The general idea is that the two print heads can be used independently to print a water-soluble tablet shell with the first print head and incorporate functional particles into the tablet shell with a second print head using different materials for each step. In this study, a modular four-particle-layered tablet computer model containing 196 cylindrical particles with a diameter of 1.4 mm, a height of 1.0 mm and a total tablet size of 22.6 × 8.5 × 6.0 mm is proposed. A first proof-of-concept study with drug-free commercially available polylactic acid filament for the particles and polyvinyl alcohol filament for the tablet shell revealed critical parameters (such as filament retraction, z-offset and water content of filaments) for the successful printing of the proposed computer model. In addition, the successfully printed model 3D-MUPS tablets and incorporated particles were characterised, revealing a reproducible manufacturing process. The printed model particles had a diameter of 1.27 ± 0.04 mm and a height of 1.05 ± 0.01 mm. One of the challenges of the new approach was to avoid particle agglomeration because of remelting processes during the printing with two print heads. 57.54 ± 18.59 % of the 196 printed particles were present as single particles. Finally, the transferability and suitability with a model API-loaded (paracetamol) hydroxypropyl methylcellulose filament for the particles and a polyvinyl alcohol tablet shell was successfully tested. On average, 80 % of paracetamol was released within 3 h (2-4 h). Overall, this work shows an innovative new manufacturing method for dose-adjustable personalised MUPS tablets but also considers new challenges arising from the different manufacturing processes.