Sustained Delivery Research Articles

Engineering a 3D network hydrogel composite membrane with Chitosan/Pluronic F127/bioactive glass for the topical administration of therapeutic agents

The primary aim of designing a topical drug delivery system is to address localized ailments by administering therapeutic agents directly to superficial areas of the body such as skin and open wounds. This study presents the engineering of a three-dimensional (3D) network hydrogel composite membrane comprising chitosan (CS), Pluronic F127 (Pl), and bioactive glass (BG) for the topical administration. In the presence of CS and Pl, glutaraldehyde forms imine bonds (Schiff base linkages) by reacting its aldehyde groups with the amino groups of the polymer chains. The hydrogel structural and chemical properties were characterized using X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR), revealed its unique composition and molecular structure. Field Emission Scanning electron microscopy (FESEM) was employed to image and investigate the morphology of the hydrogel, confirming its interconnected sheet like morphology with small beads structure. The hydrogels demonstrated excellent water retention ability as 32.93 %, further controlled degradation kinetics rate was systematically evaluated up to 14 days, and optimal swelling behavior makes it suitable for prolonged drug delivery applications. Moreover, hemocompatibility and cyto-compatibility assays yielded less than 1.1 % and above 60 %, confirming the hydrogel safety for blood contact and cell viability. Tube inversion tests confirmed its mechanical integrity, while antibacterial assays revealed its efficacy against pathogenic microorganisms. Co-culture studies demonstrated the capability of developed hydrogel to support cell growth and proliferation. In vitro drug release studies clearly reveal that the hydrogel provides a sustainable delivery system for piperacillin-tazobactam, demonstrating superior characteristics indicative of non-Fickian or anomalous diffusion. Furthermore, the membrane exhibited promising hemostatic properties, suggesting its potential for wound healing applications. Overall, this comprehensive strategy highlights the versatility of the engineered 3D network hydrogel composite membrane as a promising platform for delivering therapeutic agents locally in various biomedical applications.

Investigating a novel therapeutic composition for dry eye syndrome management: In vitro and in vivo studies

Dry eye syndrome (DES) presents a significant challenge in ophthalmic care, necessitating innovative approaches for effective management. This research article introduces a multifaceted strategy to address DES through the development of ocular inserts utilizing advanced technologies such as hot-melt extrusion (HME) and the CaliCut post-extrusion system. The formulation includes key ingredients targeting different layers of the tear film and associated inflammation, including hydroxypropyl cellulose (HPC), polyethylene glycol (PEG), castor oil, and dexamethasone. The study incorporates a Design of Experiments (DoE) approach, integrating HME and the precise stretching and cutting technique of CaliCut for manufacturing consistency and dimensional control of the inserts. The developed insert(s) have been systematically characterized for their physicochemical properties, release profile, and in vivo efficacy. In silico molecular docking studies have also been conducted to assess the binding affinities of formulation components with ocular mucin, elucidating their binding affinities. Preliminary results demonstrate promising potential for the developed insert in managing DES, offering preservative-free treatment, sustained drug delivery, and improved patient compliance. This study highlights the integration of advanced technologies and formulation strategies in ocular drug delivery for effective DES management.

SLNs and NLCs for Skin Applications: Enhancing the Bioavailability of Natural Bioactives.

Natural bioactives are mixtures of compounds extracted from plants with physicochemical properties that are usually not favorable for penetrating the skin's complex barrier. Nanoparticles have important advantages both in dermatology and cosmetology: improved solubility and stability of encapsulated phytocompounds, controlled and sustained skin delivery, and enhanced skin permeation, leading to an improved bioavailability. This review focuses on two generations of lipid-based nanoparticles: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). An extensive overview on the recent studies on SLNs and NLCs entrapping essential oils, oils, herbal extracts, and phytocompounds for topical applications is presented, emphasizing their composition, physicochemical characterization, efficacy, and methodologies used to evaluate them. This review also summarizes topical systems containing natural bioactives incorporated into SLNs and NLCs, commercially available products and registered patents in the field. SLNs and NLCs turn out to be effective nanocarriers for skin applications, offering significantly improved encapsulation efficiency, stability, and bioactives delivery. However, their full potential is underexplored. Future applications should study the encapsulation potential of new natural bioactives and show more specialized solutions that address specific requirements; an improved product performance and a pleasant sensory profile could lead to increased customer compliance with the product use.

3D-printed chitosan-pectin-sodium alginate scaffolds for post-surgical peritoneal wound dressing and sustained delivery of oxaliplatin

3D-printed chitosan-pectin-sodium alginate scaffolds for post-surgical peritoneal wound dressing and sustained delivery of oxaliplatin

Injectable Glucose-Releasing Microgels Enhance the Survival and Therapeutic Potential of Transplanted MSCs Under Ischemic Conditions.

Mesenchymal stem cell (MSC)-based therapies show potential to treat ischemic diseases owing to their versatile functions. However, sustaining MSC viability and therapeutic efficacy in ischemic tissues postengraftment remains a significant challenge. This is because, although MSCs are metabolically flexible, they fail to adapt to hypoxic conditions in the absence of glucose, leading to cell death. To overcome these issues, it is aimed to establish an injectable glucose delivery system using starch and amyloglucosidase embedded in alginate microgels. Here, starch/amyloglucosidase (S/A) microgels are engineered to continuously release glucose for seven days via enzymatic hydrolysis, thereby supporting MSC functions under ischemic conditions. In vitro tests under oxygen/glucose-deprived conditions revealed that the S/A microgels not only maintained the viability and intracellular energy but also enhanced the pro-angiogenic and immunomodulatory functions of MSCs. In vivo data further confirmed the pro-survival and pro-angiogenic effects of S/A microgels on MSCs following subcutaneous engraftment in mice. Overall, the developed S/A microgel significantly enhanced the survival and therapeutic potential of MSCs via sustained glucose delivery, highlighting its potential use in advancing MSC-based therapies for ischemic conditions.

Designing a sustainable delivery network with parcel locker systems as collection and transfer points

Collection and delivery points, both attended and fully automated, have emerged as a popular solution in last-mile delivery. They offer not only operational advantages for the delivery company but also present a pathway to mitigating the negative environmental impact of parcel delivery operations. In this study, we explore a new approach, where parcel locker systems have a dual role: as collection points for customers and as transfer points for the delivery company. We introduce a variant of the Location-Routing Problem, optimizing the strategic location and capacity size of parcel locker systems as well as the delivery routes from those points. We develop an efficient branch-and-price algorithm and apply it to a real-life case study that focuses on the design of a delivery network with parcel lockers in a residential neighborhood in the city of Groningen, the Netherlands. Our case study findings underscore that the dual role of parcel locker systems considerably reduces the travel distance of delivery vehicles, is well-suited to deal with potential future increase in demand for parcel collection, and reduces the likelihood of customers traveling to parcel locker by car.

Release Kinetic of Sustained Release Matrix Tablet of Linezolid Containing Polymer Blend.

Tuberculosis (TB) is a bacterial infection mainly affecting the lungs. TB is a major health problem worldwide and the occurrence of extensively drug-resistant TB (XDR-TB) and multidrug-resistant TB (MDR-TB) offers considerable hurdles to effective treatment and disease management. The growth of treatment-resistant Mycobacterium TB strains has prompted the investigation of alternate therapeutic techniques, including the application of sustained drug delivery. Sustained-release drugs reduce the need for frequent dosing can extend the effects of linezolid by 8 to 12 hours, thus improving the patient’s adherence to the treatment. The objective of this study is to formulate oral sustained-release linezolid tablets employing blends of polymers like hydroxy propyl methyl cellulose (HPMC)- K100M, ethyl cellulose, xanthan gum, and chitosan to provide sustained drug release. Linezolid was made into a sustained-release tablet by employing the direct compression method using different drug-polymer ratios. Formulated tablets were compared with marketed formulations to assess the similarity factor. The formulation was assessed for drug-excipient interaction, solubility, flow properties, etc. The diameter, friability, thickness, hardness, weight variation, in-vitro drug release, and drug release kinetics of compressed tablets were examined. Drug release research proved that all polymers were able to sustain drug release. Formulation (F5) with HPMC (100mg) and ethyl cellulose (100mg) resulted in 49.89% drug release after 8 hours, making it the optimal formulation. According to the kinetic model of the drug release, the Higuchi model was selected, which indicates the diffusion of the drug from an insoluble matrix. The optimized formulation showed a similarity factor of 52% with the marketed formulation, suggesting similarity in drug release between these two formulations.

Nanoemulgels: A new approach for the treatment of skin-related disorders

Skin-related disorders like psoriasis, dermatitis, acne, and wounds affect a major sector of the global population. Conventional treatment modalities exhibit limitations encompassing systemic adverse effects, suboptimal skin permeability, and variable drug release kinetics. Nanoemulsion-based hydrogels, also known as nanoemulgels, have emerged as a promising approach for topical and transdermal drug delivery, particularly in treating skin disorders. These have the advantages of nanoemulsions and hydrogels, offering enhanced therapeutic efficacy. Further, nanoemulgels can facilitate controlled and sustained drug delivery, reducing the frequency of application and improving patient compliance. These nanoemulgels hold significant prospects in topical and transdermal applications, particularly in delivering therapeutic cargo in diseases such as mycoses, atopic dermatitis, and psoriasis. This review will outline the functions of nanoemulgels, the building blocks of nanoemulgels, their formulation techniques, evaluation parameters, and their pharmacological applications. Further, an overview of the current state of research in the field of nanoemulgels, future directions, and challenges associated with nanoemulgels was also provided.

Design, Development and Characterization of Gastroretentive Floating Tablet of Levofloxacin using Natural Polymer Peanut Husk.

In the present study, levofloxacin gastroretentive floating tablet (GRFT) was formulated using peanut husk powder as a natural release modifier for providing sustained drug delivery at the stomach to effectively treat infections. Preformulation studies such as UV analysis and drug excipients study using Fourier-transform infrared (FTIR) were performed. Peanut husk powder was prepared by crushing and grinding the dried peanut husk. The GRFT formulations (GRFT1- GRFT9) were formulated using the direct compression method with varied concentrations having peanut husk powder, HPMCK4M and carbapol 934, along with other ingredients. Formulations were characterized based on the pre-compressional parameter and post-compressional parameters. The results for GRFT5 were found to be best among all batches as it showed sustained %drug release of 89.52 ± 0.3% upto 12 hours and it revealed enhanced therapeutic performance of the drug. However, in-vivo study needs to be performed for a better comparison of data with in-vitro results.

Development and Analysis of Colon-Specific, pH-Responsive Polymer Delivery of Irinotecan Hydrochloride Tablets for Colon Cancer Treatment.

For the formulation of enteric-coated tablets containing irinotecan hydrochloride, this thesis focuses on HPMC and ethylcellulose, both of which are pH- and oxidation-resistant polymers. The integrated polymer-drug tablet mixture was coated with 15% of eudragit S100 and L100, which is a methacrylic acid copolymers, that’s soluble at pH 7. Both the physical characteristics with the invitro release kinetics pattern of the enteric-coated tablets were characterized. In the invitro release study, different pH environments were used, comparable to the gastrointestinal tract (GIT): 0.1 N HCl solution for two hours, pH 6.8 phosphate buffer for three hours, and pH 7.4 phosphate buffer for six hours. Using this device, you can simulate the pH level of the mouth, the digestive tract, and the urinary tract. As a result of consistent release studies, formulation F7 released 88.2% of the drug after 12 hours. Models such as Higuchi, Korsmeyer-Peppas, and zero-order reactions were used to analyze the GIT. This directed the development of a sustained delivery pattern that may be perfect for colonic IRT administration in the eventual treatment of colon cancer. Among the nine formulations, F7 formulated with EC and HPMC extended best sustained release pattern of drug, hence it is suitable for treating colon cancer.

Bismuth-infused perivascular wrap facilitates delivery of mesenchymal stem cells and attenuation of neointimal hyperplasia in rat arteriovenous fistulas

BackgroundMesenchymal stem cells (MSCs) have emerged as novel therapies for supporting arteriovenous fistula (AVF) maturation, and bioresorbable polymeric scaffolds have enabled sustained MSC delivery into maturing AVFs. However, the radiolucency of biopolymeric wraps prevents in vivo monitoring of their integrity and location, hindering long-term preclinical investigations. MethodsWe infused bismuth nanoparticles (BiNPs) into polycaprolactone (PCL) to fabricate an electrospun perivascular wrap capable of MSC delivery and conducive to longitudinal monitoring using conventional imaging. We tested the wraps' effects on the attenuation of markers of neointimal hyperplasia (i.e., endothelial dysfunction, hypoxia, and inflammation), the leading cause of AVF failure, in rats with induced chronic kidney disease (n = 3 per time point) for the following groups: control (no wrap), PCL wrap, PCL with MSCs, PCL-Bi (BiNP-infused wrap), and PCL-Bi with MSCs. ResultsPhysicochemical characterization and in vitro biocompatibility tests revealed that BiNP infusion did not alter the wrap's non-cytotoxicity toward vascular cells, hemocompatibility, and capacity for MSC loading but facilitated long-term monitoring via micro-computed tomography. After 8 weeks, all treatment groups demonstrated significant improvement in wall-to-lumen ratio on ultrasonography (P < 0.001), neointima-to-lumen ratio on histomorphometry (P < 0.001), and attenuation of neointimal hypoxia on immunohistochemistry (P < 0.05). Compared to non-MSC wraps, MSC-loaded wraps not only attenuated endothelial dysfunction and neointimal inflammation but also reduced hypoxia and inflammation across all vascular layers. ConclusionThese results demonstrate that MSC delivery through a radiopaque polymeric wrap could enhance AVF patency outcomes through the inhibition of multiple pathways inducing AVF failure.

Preparation and Evaluation of Itraconazole Nanoparticle Lipid Carrier Gel for Dermatophytosis

Fungal infection is one of the common dermatological diseases. Drug delivery systems for topical use have shown significant advantages in targeting the drug to the action site in the body and also reduces the systemic side effects. Itraconazole was chosen as a model drug with low aqueous solubility. In the present study an attempt was made to prepare itraconazole loaded nanostructured lipid carrier (NLC). Different formulations were prepared by hot homogenization technique using solid lipid and liquid lipid (Compritol 888 &amp; Caprol PGE 860) and surfactants (Poloxamer 188, tween 80). All the Formulations were characterized for drug content, entrapment efficiency, particle size, poly dispersity index, zeta potential &amp;in vitro drug release and FTIR was done to study any interaction between excipients. The best formulation shows better drug release and entrapment efficiency 83.2%. the best formulation F3 showed better in-vitro drug release 55.46% at the end of 8th hour. The F3 was made into gel using Carbopol as a gelling agent. SEM study revealed that the NLC gel shows the particle size was found to be 500 nm in size smooth surfaces. NLC gel shows Drug release of NLC gel followed non- Fickian diffusion. NLC gel were stable at 40 ± 2ֹ°C and 75 ± 5% RH. Thus, the prepared NLC gel proved to be a potential candidate as a topical nanoparticulate sustained drug delivery system for itraconazole (BCS class II drug). keywords: Itraconazole, Nanoparticle Lipid Carrier, Lipids.

Optimizing the Fabrication of Shape-Defined Microparticles for Sustained Drug Delivery: The “Less Is More” Paradigm

Optimizing the Fabrication of Shape-Defined Microparticles for Sustained Drug Delivery: The “Less Is More” Paradigm

Ascorbyl palmitate nanofiber-reinforced hydrogels for drug delivery in soft tissues

Nanofiber-based hydrogel delivery systems have recently shown great potential in biomedical applications, specifically due to their high surface-to-volume ratio of ultra-fine nanofibers and their ability to carry low solubility drugs. Herein, we introduce a visible light-triggered in situ-gelling drug vehicle (GAP Gel) composed of ascorbyl palmitate (AP) nanofibers and gelatin methacryloyl polymer. AP nanofibers form self-assembled structures through intermolecular interactions with a hydrophobic drug-loading core. We demonstrate that the hydrophilic periphery of AP nanofibers allows them to interact with other hydrophilic molecules via hydrogen bonds. The presence of AP nanofibers significantly enhances the viscoelasticity of GAP Gel in a concentration-dependent manner. Further, GAP Gel shows in vitro biocompatibility and sustained drug delivery efficacy when loaded with a hydrophobic antibiotic. Likewise, GAP Gel shows excellent in vivo biocompatibility when implanted in immunocompetent mice in various forms. Lastly, GAP Gels maintain cell viability when cultured in a 3D-environment over 7 days, establishing it as a promising and versatile hydrogel platform for the delivery of biotherapeutics.

In situ formed reactive oxygen species-responsive dipyridamole prodrug hydrogel: Spatiotemporal drug delivery for chemoimmunotherapy

In the realm of combined cancer immunotherapy, the strategic combination of therapeutics targeting both cancer cells and macrophages holds immense potential. However, the major challenges remain on how to achieve facile spatiotemporal delivery of these therapies, allowing ease of manipulation and ensuring differential drug release for enhanced synergistic therapeutic effects. In the present study, we introduced a tumor microenvironment (TME)-adapted hydrogel with the phenylboronic acid-modified dipyridamole prodrug (DIPP) as a crosslinker. This prodrug hydrogel scaffold, 3BP@DIPPGel, could be formed in situ by a simple mixture of DIPP and poly(vinyl alcohol) (PVA), and loaded with a high ratio of 3-bromopyruvic acid (3BP). The 3BP@DIPPGel enables spatiotemporal localized delivery of dipyridamole (DIP) and 3BP with distinct release kinetics that effectively reshape the immunosuppressive TME. Upon reactive oxygen species (ROS) stimulation, 3BP@DIPPGel preferentially released 3BP, inducing tumor-specific pyroptosis via the ROS/BAX/caspase-3/GSDME signaling pathway and decreasing the secretion of chemokines such as CCL8 to counteract macrophage recruitment. Subsequently, the crosslinked DIP is released, triggering the tumor-associated macrophages (TAMs) polarization towards the immunostimulatory M1 phenotype via the CCR2/JAK2/STAT3 cascade signaling pathway. This dual action from 3BP@DIPPGel leads to the restoration of tumor cell immunogenicity with high efficacy and activation of immune cells. Furthermore, the 3BP@DIPPGel-based chemoimmunotherapy upregulates the expression of sialic-acid-binding Ig-like lectin 10 and hence sensitizing tumors to anti-CD24 therapy in the tumor-bearing mice. Therefore, this strategy can have significant potential in the prevention of tumor metastases and recurrence. To the best of our understanding, this study represents a pioneering showcase of tumor pyroptosis, induced by glycolytic inhibitors, which can be effectively coordinated with DIP-mediated TAM polarization for immune activation, offering a new paradigm for differentially sustained drug delivery to foster cancer immunotherapy.

A thermosensitive hydrogel for the sustained delivery of exosomes extracted from menstrual blood mesenchymal stem cells and frizzled antibody on triple-negative breast cancer cells in vitro

Due to the heterogeneity of triple-negative breast cancer (TNBC), conventional treatments usually respond poorly and effective targeted therapies for this type of cancer are rare. Wnt signaling plays an important role in breast cancer metastasis and proliferation, as shown by analyzes of gene expression profiling and genome-wide sequencing. In addition, the role of endometrial cells in regulating angiogenesis during the menstrual cycle as an angiostatic state associated with the end of the cycle has been well established. Therefore, exosomes of menstrual blood-derived stem cells (Exo-Mens) could play a role as effective inhibitors of tumor-induced angiogenesis. However, repeated administration and systemic toxicity are major problems with conventional drug delivery methods. To minimize these drawbacks and maximize the therapeutic benefits of the drugs, hydrogels provide convenient methods for drug delivery. The aim of this study was therefore to investigate the effects of hydrogels containing Exo-Mens and Frizzled antibodies (anti-FZ) on breast cancer cells. First, the optimization and characterization of the hydrogel were performed, then the cell lines (MDA-MB-231 and HUVEC) were studied in four groups: Hydrogel (control), Hydrogel with anti-FZ, Exo-Mens and FZ + Exo. First, the IC50 of anti-FZ and Exo-Mens was determined and the degradability and release pattern of the investigated groups were measured. Western blot (VEGF, HIF-1α) and qRT-PCR (VEGF, HIF-α and KDR) were performed for the HUVEC cell line and scratch tests, colony formation and apoptosis for the MDA-MB-231 cell line. In addition, invasion and migration were performed for both cell lines. Our results showed that the optimal hydrogel is a suitable option for sustained release of the studied groups. The loaded compounds could be released within 7 days. The angiogenic activity of dual anti-FZ and Exo-Mens within the hydrogel, showed a significant shift in the expression of pro-angiogenic genes and related proteins, including HIF-1α, VEGF-A and KDR, in the treated HUVECs. The hydrogel treatment groups were also able to reduce migration and invasion in both cell lines compared to the control group. In addition, a reduction in colony formation and an increase in apoptosis were observed, especially in the cancer cells exposed to anti-FZ. Angiogenesis as well as proliferation and invasion of tumor cells were inhibited by the developed hydrogel system containing anti-FZ, Exo-Mens and a combination of both with slow release.

Emerging Applications of Herbal-Based Nanocosmeceuticals for Beauty and Skin Therapy

: Herbal cosmeceuticals are a rapidly expanding sector of the personal care industry, and their use has greatly expanded over time. The advancement of research and development is demonstrated by nanotechnology, which boosts product efficacy by delivering innovative solutions. The application of nanotechnology is growing in the field of cosmeceuticals to address numerous shortcomings of conventional herbal products. Lower penetration and high compound instability of various cosmetic products for prolonged and enhanced compound delivery to beauty-based skin therapy are the main problems with the use of phyto-based cosmeceuticals. Nanosized delivery technologies are currently being used in cosmeceutical industries and products for prolonged and improved delivery of phyto-derived bioactive chemicals to solve these drawbacks. The aseptic sensation of many cosmeceutical products is improved by nanosizing phytocompounds, which also improve skin-protective properties and sustained delivery. Nanocosmeceuticals are now commonly utilized on skin, hair, lips, and nails to treat disorders including wrinkles, photoaging, hyperpigmentations, dandruff, hair damage, chapped lips, etc. Some of the cutting-edge nanotechnologies now being used for improved delivery of the phytoconstituents in skin care therapy include liposomes, ethosomes, glycerosomes, transferosomes, niosomes, phytosomes, nanostructured lipid carriers, solid lipid nanoparticles, polymeric nanoparticles, nanoemulsions, nanogels, etc. The advantages of these novel nanocarriers include improved skin penetration, controlled and prolonged drug release, increased stability, site-specific targeting, high entrapment efficiency, and improved bioavailability. Several phytoconstituents such as curcumin, aloe vera, resveratrol, lycopene, tocopherol, quercetin, catechins, and lutein have been successfully nanosized by employing various delivery technologies and incorporated in various gels, lotions, and creams for skin, lip, hair, and nail care for their sustained effects. The present article primarily focuses on the use of phytocompounds in various cosmeceutical products, diverse classes of innovative nanocarriers employed for delivering herbal nanocosmeceuticals, and the use of various phytobioactive compounds in novel nanocosmeceutical formulations to improve skin-based therapy.

Will e-consumers wait longer for a more sustainable on-demand food delivery? A choice experiment using green information

ABSTRACT The rapid growth of on-demand food delivery has sparked concerns about its societal and environmental impact. While alternative solutions like group ordering and electric bikes aim to address these issues, their adoption is hindered by inconveniences, mainly due to the longer delivery times, which are critical in food delivery. Price incentives such as discounts have traditionally been used as compensation, but questions about their long-term feasibility persist. This study assesses whether providing carbon footprint information can reduce the reliance on price incentives, especially when compensating for longer delivery times. Through a mixed-design experiment with 215 e-consumers in Greater Jakarta, we found that green information effectively encourages more sustainable delivery choices, similar to discounts. However, combining green information with discounts adds little value, suggesting that emphasizing green information alone could reduce financial costs and foster intrinsic motivation. Additionally, female and younger consumers are more responsive to green information, indicating the potential for targeted sustainability efforts in the on-demand food delivery sector.

Titanium Dioxide Nanomaterials: Progress in Synthesis and Application in Drug Delivery.

Background: Recent developments in nanotechnology have provided efficient and promising methods for the treatment of diseases to achieve better therapeutic results and lower side effects. Titanium dioxide (TiO2) nanomaterials are emerging inorganic nanomaterials with excellent properties such as low toxicity and easy functionalization. TiO2 with special nanostructures can be used as delivery vehicles for drugs, genes and antigens for various therapeutic options. The exploration of TiO2-based drug delivery systems shows great promise for translating nanotechnology into clinical applications; Methods: Comprehensive data on titanium dioxide were collected from reputable online databases including PubMed, GreenMedical, Web of Science, Google Scholar, China National Knowledge Infrastructure Database, and National Intellectual Property Administration; Results: In this review, we discuss the synthesis pathways and functionalization strategies of TiO2. Recent advances of TiO2 as a drug delivery system, including sustained and controlled drug release delivery systems were introduced. Rigorous long-term systematic toxicity assessment is an extremely critical step in application to the clinic, and toxicity is still a problem that needs to be closely monitored; Conclusions: Despite the great progress made in TiO2-based smart systems, there is still a great potential for development. Future research may focus on developing dual-reaction delivery systems and single-reaction delivery systems like redox and enzyme reactions. Undertaking thorough in vivo investigations is necessary prior to initiating human clinical trials. The high versatility of these smart drug delivery systems will drive the development of novel nanomedicines for personalized treatment and diagnosis of many diseases with poor prognosis.

Novel inhalable nano-based/microparticles for enhanced sustained pulmonary delivery of remdesivir - A patient malleable treatment for coronaviruses infection: In vitro aerosolization, cytotoxicity assays and antiviral activity studies

Remdesivir (RDV) is an antiviral used in potential treatment of SARS-COV-2 infection during the COVID-19 pandemic worldwide. However, it is still limited to IV administration for hospitalized patients. Therefore, we report herein successful development of RDV-loaded nanosuspensions (NS) using polycaprolactone and pluronic® F127, for the first time. The optimized RDV-NS was further loaded into inhalable nano-based/microparticles (OLN-microparticles) via co-spray drying with hyaluronic acid and mannitol. OLN-microparticles exhibited high yield value ∼80.56 %, with satisfactory entrapment efficiency and drug loading percent ∼97.27 ± 1.84 % and 3.92 ± 0.07 %, respectively. Carr's index was equal to 22.7 ± 11.67 % indicating good flowability properties. Scanning electron microscopic analysis showed spherical-shaped particles. Transmission electron microscope demonstrated grape-shaped clumps surface porosity. OLN-microparticles exhibited excellent aerodynamic features including; emitted fraction ∼97.46 ± 1.70 %, respirable particle fraction 53.77 ± 0.2 %, effective inhalation index 72.39 ± 1.40 %, and mass median aerodynamic diameter 2.25 ± 0.01 μm. Compared to plain RDV, OLN-microparticles showed significantly enhanced sustained release (p < 0.0001) with 1.5 and 1.9 fold increase at 24 and 48 h, respectively in Gamble's solution. OLN-microparticles also showed favorable cytotoxic profile with CC50 ∼ 252.0 μg/mL, inhibitory concentration (IC50) 13.08 μg/mL, and safety index (SI) 19.26 which is 1.3 fold higher compared to plain RDV. The Optimal release profile of OLN-microparticles enabled controlled and sustained release with enhanced cellular uptake. Hence, OLN-microparticles represented an efficient alternative form of dry powder for inhalation for deep and targeted pulmonary delivery of RDV, outweighing limitations accompanied with IV administration. It can provide self-administered and malleable access of treatment for SARS-COV-2 infected patients.