Delivery System Research Articles

Starch-based encapsulation to enhance probiotic viability in simulated digestion conditions

This research aims to meet the demand for efficient delivery systems in the food, nutraceutical, and pharmaceutical industries. The study involved the synthesis of starch-based nanoparticles for potential application in the encapsulation of Lactobacillus rhamnosus. Various techniques such as zeta sizer, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM) were used to characterize the encapsulated probiotics in microbeads. The results showed 85.00 % encapsulation efficiency of beads. Microscopic analysis revealed that the probiotics accumulated within the wall material and formed small, smooth polygonal granules on the capsule surface. XRD analysis confirmed the presence of amorphous humps and some crystallinity of nanoparticles in the capsules. Moreover, encapsulation significantly improved probiotic viability under simulated gastrointestinal conditions. This study highlights the potential of starch-based nanoparticles to enhance the stability and viability of probiotics, demonstrating their potential applications across various industrial sectors. Further research should focus on investigating the long-term stability and functional efficacy of encapsulated probiotics in microbeads for real-world applications.

Locally Acting Budesonide-Loaded Solid Self-Microemulsifying Drug Delivery Systems (SMEDDS) for Distal Ulcerative Colitis

Locally Acting Budesonide-Loaded Solid Self-Microemulsifying Drug Delivery Systems (SMEDDS) for Distal Ulcerative Colitis

Nanorevolution Unleashing the Power of Nanotechnology

Abstract: Nanotechnology, the manipulation of matter at the nanoscale, has been an extraordi-nary scientific frontier that has revolutionized various fields, with one of the most promising ap-plications being in the realm of medicine. Nanomedicine, an interdisciplinary field at the intersec-tion of nanotechnology and medicine, holds tremendous potential to transform the landscape of healthcare, diagnosis, and treatment. This abstract delves into the burgeoning advancements of nanotechnology in nanomedicine, highlighting its significance, potential benefits, and ethical con-siderations. The primary focus of nanomedicine is to engineer and utilize nanoscale materials, such as nano-particles and nanostructures, to improve the effectiveness and precision of medical interventions. Nano-sized drug delivery systems can target specific cells or tissues, enhancing therapeutic out-comes and reducing side effects. These nanocarriers can penetrate biological barriers and accu-mulate at disease sites, enabling more efficient drug delivery and increasing the bioavailability of therapeutic agents. Furthermore, nanotechnology has opened new horizons in medical imaging. Nanoparticles can be engineered to be responsive to certain diseases or conditions, providing val-uable information for early detection and precise diagnosis. Novel contrast agents based on na-nomaterials have the potential to revolutionize imaging techniques, offering higher sensitivity and specificity, ultimately leading to improved patient outcomes. Beyond diagnostics and drug delivery, nanotechnology is fostering breakthroughs in regenerative medicine. Nanomaterials can act as scaffolds, guiding tissue repair and promoting cellular regen-eration. By harnessing the unique properties of nanoscale materials, tissue engineering, and organ transplantation may witness unparalleled advancements, bringing hope to countless patients awaiting life-saving treatments. However, the unprecedented potential of nanomedicine also rais-es ethical concerns that demand careful consideration. As nanotechnology progresses, concerns about the safety of nanomaterials, potential toxicity, and long-term effects must be addressed to ensure responsible and sustainable development.

Construction of an intelligent pH-sensitive hydrogel drug delivery system and its application in gastric ulcer treatment

The occurrence of gastric ulcer is mainly due to the damage of gastric mucosa which leads to inward flow of gastric acid to corrode the gastric cavity, thus producing gastric fever, vomiting, loss of appetite and other adverse reactions. Prevention and treatment of such injuries are crucial. In this study, a simple and non-toxic composite hydrogel (PLGA/CMCS) was prepared through Schiff base reaction between poly(lactic-co-glycolic acid) (PLGA) and carboxymethyl cellulose (CMCS). Subsequently, compound 1 was loaded onto it to construct PLGA/CMCS@1. A series of structural characterization and performance experiments were conducted on these novel hydrogel polymers. Furthermore, we detected the gene expression level of Fas/FasL apoptotic pathway after treating the cells with different concentrations of PLGA/CMCS@1 through an ethanol-induced damaged gastric mucosal epithelial cell model. The results showed that the system was able to significantly regulate the expression of genes related to the apoptotic pathway. The system can regulate the Fas/FasL apoptosis pathway to treat gastric ulcer.

Developments in Emerging Topical Drug Delivery Systems for Ocular Disorders.

According to the current information, using nano gels in the eyes have therapeutic benefits. Industry growth in the pharmaceutical and healthcare sectors has been filled by nanotechnology. Traditional ocular preparations have a short retention duration and restricted drug bioavailability because of the eye's architectural and physiological barriers, a big issue for physicians, patients, and chemists. In contrast, nano gels can encapsulate drugs within threedimensional cross-linked polymeric networks. Because of their distinctive structural designs and preparation methods, they can deliver loaded medications in a controlled and sustained manner, enhancing patient compliance and therapeutic efficacy. Due to their excellent drugloading capacity and biocompatibility, nano-gels outperform other nano-carriers. This study focuses on using nano gels to treat eye diseases and provides a brief overview of their creation and response to stimuli. Our understanding of topical drug administration will be advanced using nano gel developments to treat common ocular diseases such as glaucoma, cataracts, dry eye syndrome, bacterial keratitis, and linked medication-loaded contact lenses and natural active ingredients.

Advances in Aerogels Formulations for Pulmonary Targeted Delivery of Therapeutic Agents: Safety, Efficacy and Regulatory Aspects.

Aerogels are the 3D network of organic, inorganic, composite, layered, or hybrid-type materials that are used to increase the solubility of Class 1 (low solubility and high permeability) and Class 4 (poor solubility and low permeability) molecules. This approach improves systemic drug absorption due to the alveoli's broad surface area, thin epithelial layer, and high vascularization. Local therapies are more effective and have fewer side effects than systemic distribution because inhalation treatment targets the specific location and raises drug concentration in the lungs. The present manuscript aims to explore various aspects of aerogel formulations for pulmonary targeted delivery of active pharmaceutical agents. The manuscript also discusses the safety, efficacy, and regulatory aspects of aerogel formulations. According to projections, the global respiratory drug market is growing 4-6% annually, with short-term development potential. The proliferation of literature on pulmonary medicine delivery, especially in recent years, shows increased interest. Aerogels come in various technologies and compositions, but any aerogel used in a biological system must be constructed of a material that is biocompatible and, ideally, biodegradable. Aerogels are made via "supercritical processing". After many liquid phase iterations using organic solvents, supercritical extraction, and drying are performed. Moreover, the sol-gel polymerization process makes inorganic aerogels from TMOS or TEOS, the less hazardous silane. The resulting aerogels were shown to be mostly loaded with pharmaceutically active chemicals, such as furosemide-sodium, penbutolol-hemisulfate, and methylprednisolone. For biotechnology, pharmaceutical sciences, biosensors, and diagnostics, these aerogels have mostly been researched. Although aerogels are made of many different materials and methods, any aerogel utilized in a biological system needs to be made of a substance that is both biocompatible and, preferably, biodegradable. In conclusion, aerogel-based pulmonary drug delivery systems can be used in biomedicine and non-biomedicine applications for improved sustainability, mechanical properties, biodegradability, and biocompatibility. This covers scaffolds, aerogels, and nanoparticles. Furthermore, biopolymers have been described, including cellulose nanocrystals (CNC) and MXenes. A safety regulatory database is necessary to offer direction on the commercialization potential of aerogelbased formulations. After that, enormous efforts are discovered to be performed to synthesize an effective aerogel, particularly to shorten the drying period, which ultimately modifies the efficacy. As a result, there is an urgent need to enhance the performance going forward.

Engineering PSMA-targeted nanoparticles co-encapsulating mitoxantrone and indocyanine green for precise combinatory therapy in prostate cancer

Prostate cancer is the 2nd most common cancer in men worldwide. Chemotherapeutic treatment of prostate cancer with mitoxantrone (MTX) has limited efficacy due to severe side effects in which cardiotoxicity and myelosuppression are the two major causes of its dose-limiting toxicity. This study aimed to obtain a poly (lactic-co-glycolic acid) (PLGA) nanoparticle that can precisely deliver MTX to the prostate cancer cells overexpressing the Prostate-specific membrane antigen (PSMA) receptor-sparing healthy tissues and co-loading Indocyanine green (ICG) as a fluorescent photothermal/photodynamic agent for precise combinatory therapy in prostate cancer. The biocompatible polymer PLGA was covalently modified with the peptide of sequence (WQPDTAHHWATL) to actively target the PSMA receptor. Factors like the peptide-to-polymer ratio or the peptide's orientation during the polymer's chemical modification were investigated to enhance the active targeting of the nanoparticles (NPs). NPs were characterised using dynamic light scattering, scanning electron microscopy, and UV–vis spectroscopy to determine their morphological and colloidal properties and optimal MTX and ICG encapsulation efficiency. Quantitative FACS analysis of LNCaP and PC-3 cells incubated with Nile Red-labelled non-targeted PLGA or PLGA-PSMA targeted NPs was assessed to identify the best formulation that bound selectively to PSMA. The orientation of the peptide conjugated to the polymer, which has the C-terminal end of the peptide sequence accessible for interaction with the cell receptor, maximises the targeting capacity of the system. Photothermal experiments using 808 nm near-infrared laser irradiation were conducted, and cytotoxicity was assessed using the resazurin viability assay. Remarkably, our results confirmed the safety and efficacy of a targeted and activatable therapy using polymeric NPs functionalised with the peptide and co-loaded with MTX and ICG. This pioneer nanosystem opens new perspectives for exploring advanced targeted delivery in prostate cancer. It offers a straightforward methodology for functionalising drug delivery systems with bioactive peptides that can be applied to different types of cancer.

Tailored graphene nanoparticles for bio-medical application: Preliminary in vitro characterization of the functionality in model cell lines

Thanks to an environmentally friendly physical treatment of high purity graphite, a good control of the structure of graphene nanoparticles (GNPs) has been obtained with the production of stable and reproducible GNPs water dispersions. The preparation protocol entailed ball-milling of synthetic graphite followed by sonication in water and centrifugation/separation procedures. This way, two different GNPs samples with slightly different structural characteristics were harvested: TOP60, showing an average lateral size of the graphene layers < L> = 70 nm and average number of stacked layers < N> = 4, and BOTTOM60, with < L> = 120 nm and < N> = 6. A detailed structural characterization of GNPs was performed as mandatory pre-requisite to build reliable structure/properties correlations, in terms of both bio-medical efficacy and toxicity, aiming at a rationale design of tailored materials for applications in biological environments.To this end, in this study GNPs were thoroughly characterized, focusing on cytotoxicity, cellular up-take, and inflammatory response, by testing their effect in different cell lines. BOTTOM60 GNPs in culture medium and in the presence of cells showed a tendency to form big aggregates, phenomenon that was probably responsible for their cytotoxicity at high concentrations. On the other hand, TOP60 GNPs showed a diverse behavior depending on the cell type under investigation. Indeed, the nanoparticles were internalized by cells specialized in endo/phagocytosis, such as astrocytoma cells, but not by carcinoma cells of epithelial origin. Moreover, TOP60 GNPs caused a reduction of proliferation only at high concentration and did not trigger an inflammatory response in THP-1-derived macrophages.The evidence here collected paves the way for further investigations towards the development of GNPs-based drug delivery systems.

Usefulness of a dedicated laser-cut metal stent with an anchoring hook and thin delivery system for endoscopic ultrasound-guided hepaticogastrostomy in malignant biliary obstruction: a prospective multicenter trial (with video).

Background and AimsEUS-guided hepaticogastrostomy (EUS-HGS) carries a risk of serious adverse events (AEs). A newly designed, partially covered laser-cut stent with antimigration anchoring hooks and a thin tapered tip (7.2F), called a Hook stent, has been developed to prevent serious AEs associated with EUS-HGS. The present prospective multicenter clinical trial evaluated the efficacy and safety of the Hook stent for EUS-HGS after failure of ERCP in patients with unresectable malignant biliary obstruction. MethodsThe primary endpoint was the rate of clinical success, and the secondary endpoints were the rates of technical success, AEs, recurrent biliary obstruction (RBO), procedure success without using a tract dilation device, re-intervention for RBO, time to RBO (TRBO) and overall survival (OS). ResultsA total of 38 patients underwent EUS-HGS using the Hook stent. Its technical and clinical success rates in patients undergoing EUS-HGS were 100% and 92.1%, respectively. The procedure success rate without using a tract dilation device was 94.7%. Four (10.5%) patients developed early AEs, but there were no severe AEs such as stent migration. RBO developed in 26.3% of patients. Re-intervention for RBO had a 100% success rate. The median TRBO was not reached, and the median OS was 191 days. ConclusionsEUS-HGS using the Hook stent demonstrated a high clinical success rate, a low rate of early AEs, and an acceptable stent patency. The Hook stent is safe and feasible for use in patients undergoing EUS-HGS.

Folic Acid - Based Hydrogels Co-assembled with Protocatechuic Acid for Enhanced Treatment of Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) presents a significant therapeutic challenge due to the need for oral drug delivery systems that withstand acidic environment of stomach while effectively targeting intestinal inflammation. To address this issue, we created a novel hydrogel system based on a folic acid (FA)-dopamine (DA) conjugate, co-assembled with protocatechuic acid (PCA), to form F-DP hydrogels. These hydrogels demonstrated robust anti-gastric acid, mucosal adhesive, and injectable properties, enhancing their efficacy for targeted delivery. In DSS-induced colitis mouse models, treatment with F-DP hydrogels resulted in significant therapeutic improvements, including increased body weight, reduced disease activity index (DAI), and maintained colon length. Biochemical assays revealed that F-DP hydrogels significantly enhanced antioxidant enzyme activities (GSH and SOD) and reduced oxidative stress markers (NO and MDA). Histological assessments confirmed effective repair of the colonic mucosal barrier, restoration of tight junction protein ZO-1, and reduction of inflammatory lesions. Furthermore, immunofluorescence staining indicated that F-DP hydrogels facilitated macrophages polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, thereby reducing inflammation and promoting tissue repair. Our study demonstrates that F-DP hydrogels show significant potential for improving IBD treatment through enhanced gastric resistance, intestinal adhesion, and synergistic anti-inflammatory effects, warranting further investigation for clinical applications.

Zein-PEG nanoparticles modified with hyaluronic acid for paclitaxel delivery in SKOV3 ovarian cancer cells

Ovarian cancer is a leading gynecological cancer globally. This study aimed to develop hyaluronic acid-modified polyethylene glycol conjugated zein nanoparticles (zein-PEG/HA NPs) to enhance paclitaxel (PTX) cytotoxicity in SKOV3 ovarian cancer cells. Zein-PEG, with its amphiphilic nature, self-assembled into micelles to encapsulate the hydrophobic PTX, while the PEG shell retained micelle stability and hemolytic resistance. PTX@zein-PEG micelles (17.2 ± 0.3 mV) were complexed with negatively charged HA through electrostatic interactions, resulting in PTX@zein-PEG/HA NPs with a negative zeta potential of −15.3 ± 1.1 mV. Cellular uptake of fluorescent zein-PEG/HA NPs was higher than zein-PEG micelles in CD44-overexpressing SKOV3 cells. Additionally, PTX@zein-PEG/HA NPs demonstrated significantly greater cytotoxicity than free PTX and PTX@zein-PEG micelles, with IC50 values reduced by 6.13-fold and 3.58-fold, respectively. PTX@zein-PEG/HA NPs induced the highest expression levels of apoptotic proteins, particularly PARP, in SKOV3 cells compared to PTX@zein-PEG NPs and free PTX. In summary, PTX@zein-PEG/HA NPs demonstrated potential as a delivery system for PTX in ovarian cancer.

Advancements in Engineering Tetrahedral Framework Nucleic Acids for Biomedical Innovations.

Tetrahedral framework nucleic acids (tFNAs) are renowned for their controllable self-assembly, exceptional programmability, and excellent biocompatibility, which have led to their widespread application in the biomedical field. Beyond these features, tFNAs demonstrate unique chemical and biological properties including high cellular uptake efficiency, structural bio-stability, and tissue permeability, which are derived from their distinctive 3D structure. To date, an extensive range of tFNA-based nanostructures are intelligently designed and developed for various biomedical applications such as drug delivery, gene therapy, biosensing, and tissue engineering, among other emerging fields. In addition to their role in drug delivery systems, tFNAs also possess intrinsic properties that render them highly effective as therapeutic agents in the treatment of complex diseases, including arthritis, neurodegenerative disorders, and cardiovascular diseases. This dual functionality significantly enhances the utility of tFNAs in biomedical research, presenting valuable opportunities for the development of next-generation medical technologies across diverse therapeutic and diagnostic platforms. Consequently, this review comprehensively introduces the latest advancements of tFNAs in the biomedical field, with a focus on their benefits and applications as drug delivery nanoplatforms, and their inherent capabilities as therapeutic agents. Furthermore, the current limitations, challenges, and future perspectives of tFNAs are explored.

Dosimetry for FLASH and other non-standard radiotherapy sources

We review current dosimetry practices for non-standard radiotherapy sources. We classify radiotherapy sources as established, variations of established, or novel. Our review concentrates on novel sources including ultra-high dose-rate (FLASH) sources and some that have yet to be used for clinical radiotherapy. Factors which differentiate non-standard sources include dose-rate, temporal pulse structure, spatial fractionation, focusing, the presence of magnetic fields, and energy range. For the most part we exclude techniques which use materials inside the tumor to modify the dose. Dosimetry techniques include ionization chambers, film, alanine, calorimetry, and solid-state detectors. We review dosimetry only, neglecting other issues such as beam monitoring, patient delivery systems and treatment planning.

Supercritical CO2 assisted bioMOF drug encapsulation and functionalization for delivery with a synergetic therapeutic value

Despite the impressive characteristics of biological metal organic frameworks (bioMOFs) for their use as drug delivery systems (DDs), there are still some parameters related to their structural stability and processing routes that have decelerated their realistic application in this field. Both drawbacks are unraveled in this work for the microporous bioMOF CaSyr-1 by using supercritical CO2 (scCO2) to load the bioMOF with the anti-tubercular isoniazid (INH) drug, and functionalize its external surface with a hydrophobic protective layer of stearate (S). The hydrophobicized CaSyr-1(INH)/S vehicle is further coated with a neutral surfactant (PS60) to enhance the wettability of the system. In vitro tests, related to drug carrier biocompatibility and drug release in body simulated fluids, are performed to demonstrate potential prospective of the designed DDs in pharmacy. The synthetized product displayed total biocompatibility even at high concentrations, and the particle size and dissolution rate showed to be adequate for pulmonary administration.

Assessing the structural and electronic features of C24, B12C12 and Al12C12 fullerenes for the adsorption of methimazole to develop potential drug delivery systems

The methimazole (MZOL) adsorption by each of representative C24, B12C12, and Al12C12 fullerenes was investigated based on density functional theory (DFT) calculations in an attempt for developing drug delivery systems. The quantum chemical calculations suggested successful formations of MZOL…C24, MZOL…B12C12, and MZOL…Al12C12 complexes. However, the MZOL drug substance was decomposed in the MZOL…C24 system by shifting one hydrogen atom to the fullerene side whereas the original MZOL structure was remained unchanged in the MZOL…B12C12 and MZOL…Al12C12 complexes; the MZOL…B12C12 was the most stable system even in the water and 1-octanol phases. For the formation of complexes, the sulfur atom of MZOL had the significant role in the interactions and a complementary interaction assisted it. By the electronic molecular orbital features, the studied complexes were distinguishable and the role of fullerene was dominant for managing the whole complex system. These results might be used for a fullerene-based nano-carrier drug delivery system.

A comparative DFT study of beryllium oxide (Be12O12) and boron nitride (B12N12) nanocages as potent drug delivery systems for allopurinol drug

A comparative DFT study of beryllium oxide (Be12O12) and boron nitride (B12N12) nanocages as potent drug delivery systems for allopurinol drug

Chitosan Based Injectable Cryospheres as a Potential Biopolymeric Carrier for Drug Delivery Systems: Characterization, Biocompatibility and Drug Release

Chitosan Based Injectable Cryospheres as a Potential Biopolymeric Carrier for Drug Delivery Systems: Characterization, Biocompatibility and Drug Release

Effect of material properties and extrusion process parameters on permeability of etonogestrel in ethylene vinyl acetate copolymer (EVA) films

Ethylene vinyl acetate copolymers (EVA) have been extensively used in controlled drug delivery systems due to its good biocompatibility and tunable applicability based on simple variations in vinyl acetate (VA) content. We investigated impacts of material properties of EVA, including VA content and molecular weight, as well as extrusion process parameters, including draw down ratio and cooling rate, on permeability of etonogestrel in EVA films. Among all factors studied, the VA content was the most dominant factor that controls drug permeability by affecting crystallinity of EVA. MW, DDR, and cooling rate exhibited less significant effects. The impacts of these factors on crystallinity, crystallite size, and degree of crystalline orientation of EVA were characterized using polarized light microscope, differential scanning calorimetry (DSC) and wide-angle X-ray scattering (WAXS). Based on the solution-diffusion model, the mechanisms by which the crystalline properties controlled drug solubility and diffusivity in EVA were discussed. These results can be applied to investigate the effects of material properties of EVA and manufacturing process conditions on drug release properties of reservoir-type EVA-based drug delivery systems with a rate-controlling membrane.

Phytoactive drugs used in the treatment of Alzheimer's disease and dementia.

The prevalence of Alzheimer's disease and other forms of dementia is increasing worldwide, and finding effective treatments for these conditions is a major public health challenge. Natural bioactive drugs have been identified as a promising source of potential treatments, due to their ability to target multiple pathways and their low toxicity. This paper reviews the current state of research on natural bioactive drugs used in the treatment of Alzheimer's disease and other dementias. The paper summarizes the findings of studies on various natural compounds, including curcumin, resveratrol, caffeine, genistein, quercetin, GinkoBiloba, Withaniasomnifera, Ginseng Brahmi, Giloy, and huperzine, and their effects on cognitive function, neuroinflammation, and amyloid-beta accumulation. In this review, we discuss the mechanism of action involved in the treatment of Alzheimer's disease. The paper also discusses the challenges associated with developing natural bioactive drugs for dementia treatment, including issues related to bioavailability and standardization. Finally, the paper suggests directions for future research in this area, including the need for more rigorous clinical trials and the development of novel delivery systems to improve the efficacy of natural bioactive drugs. Overall, this review highlights the potential of natural bioactive drugs as a promising avenue for the development of safe and effective treatments for Alzheimer's disease and other dementias.

Evaluating Various Lactose Types as Solid Carriers for Improving Curcumin Solubility in Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDSs) for Oral Administration

Curcumin, a bioactive compound derived from turmeric, possesses numerous pharmaceutical properties; however, its poor aqueous solubility and permeability result in low bioavailability. This study aims to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) using different lactose types as solid carriers for the oral administration of curcumin to enhance its solubility. The system comprised curcumin, an oil phase, and a surfactant. Jasmine oil, as the oil phase, and Cremophor® RH40, as the surfactant, were selected due to their superior ability to solubilize curcumin. A microemulsion was then prepared using a ternary phase diagram. The liquid SNEDDSs were converted into S-SNEDDSs by employing three solid carriers: Tablettose® 80, FlowLac® 100, and GranuLac® 200. Dissolution studies conducted in simulated gastric fluid demonstrated a significant improvement in curcumin solubility in the S-SNEDDS formulations compared to curcumin powder. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses confirmed the appearance of curcumin in the S-SNEDDS, while Fourier-transform infrared (FTIR) spectroscopy indicated compatibility between the excipients and curcumin. Additionally, an accelerated stability study conducted over four weeks at 40 °C and 75% relative humidity showed no significant changes in the physical appearance of the S-SNEDDS formulations. These findings suggest that the S-SNEDDS formulation effectively enhances curcumin’s solubility, potentially improving its bioavailability for oral administration.