Conventional Delivery Methods Research Articles

Topical Nanoliposomal Collagen Delivery for Targeted Fibril Formation by Electrical Stimulation.

Collagen is a complex, large protein molecule that presents a challenge in delivering it to the skin due to its size and intricate structure. However, conventional collagen delivery methods are either invasive or may affect the protein's structural integrity. This study introduces a novel approach involving the encapsulation of collagen monomers within zwitterionic nanoliposomes, termed Lip-Cols, and the controlled formation of collagen fibrils through electric fields (EF) stimulation. The results reveal the self-assembly process of Lip-Cols through electroporation and a pH gradient change uniquely triggered by EF, leading to the alignment and aggregation of Lip-Cols on the electrode interface. Notably, Lip-Cols exhibit the capability to direct the orientation of collagen fibrils within human dermal fibroblasts. In conjunction with EF, Lip-Cols can deliver collagen into the dermal layer and increase the collagen amount in the skin. The findings provide novel insights into the directed formation of collagen fibrils via electrical stimulation and the potential of Lip-Cols as a non-invasive drug delivery system for anti-aging applications.

Nanotech for Crop Protection: Utilizing Nanoparticles for Targeted Pesticide Delivery

The use of pesticides plays a vital role in agriculture for protecting crops from pests and diseases. However, conventional delivery methods have drawbacks including toxicity, lack of efficiency, and negative environmental impacts. Nanotechnology offers solutions through nano-enabled smart pesticide delivery systems. These utilize nanoparticles as carriers that can encapsulate, absorb, or bind pesticides. Nanoparticles like liposomes, polymer nanoparticles, dendrimers, nanoemulsions, and nanocapsules allow for targeted and controlled release directly onto crops and pests. This improves pesticide efficacy while reducing toxicity and leakage into soil and water systems. Additional functionalization of nanoparticles can also improve targeting, uptake, and controlled environmental release. Examples include using ligands for binding to plant surfaces and pH-responsive nanoparticles that release pesticides following uptake by pests. The use of nanotechnology allows minimal use of pesticides, reducing environmental contamination and exposure risks. Challenges remain such as higher costs,Scaling up fabrication, assessing ecological impacts, and lack of standardized regulations. Further research and development of nano-enabled pesticide delivery can pave the way for next-generation crop protection solutions.

Sustainable Silk-Based Particulate Systems for the Controlled Release of Pharmaceuticals and Bioactive Agents in Wound Healing and Skin Regeneration.

The increasing demand for innovative approaches in wound healing and skin regeneration has prompted extensive research into advanced biomaterials. This review focuses on showcasing the unique properties of sustainable silk-based particulate systems in promoting the controlled release of pharmaceuticals and bioactive agents in the context of wound healing and skin regeneration. Silk fibroin and sericin are derived from well-established silkworm production and constitute a unique biocompatible and biodegradable protein platform for the development of drug delivery systems. The controlled release of therapeutic compounds from silk-based particulate systems not only ensures optimal bioavailability but also addresses the challenges associated with conventional delivery methods. The multifaceted benefits of silk proteins, including their inherent biocompatibility, versatility, and sustainability, are explored in this review. Furthermore, the intricate mechanisms by which controlled drug release takes place from silk-based carriers are discussed.

Targeted Macrophage CRISPR-Cas13 mRNA Editing in Immunotherapy for Tendon Injury.

CRISPR-Cas13 holds substantial promise for tissue repair through its RNA editing capabilities and swift catabolism. However, conventional delivery methods fall short in addressing the heightened inflammatory response orchestrated by macrophages during the acute stages of tendon injury. In this investigation, macrophage-targeting cationic polymers are systematically screened to facilitate the entry of Cas13 ribonucleic-protein complex (Cas13 RNP) into macrophages. Notably, SPP1 (OPN encoding)-producing macrophages are recognized as a profibrotic subtype that emerges during the inflammatory stage. By employing ROS-responsive release mechanisms tailored for macrophage-targeted Cas13 RNP editing systems, the overactivation of SPP1 is curbed in the face of an acute immune microenvironment. Upon encapsulating this composite membrane around the tendon injury site, the macrophage-targeted Cas13 RNP effectively curtails the emergence of injury-induced SPP1-producing macrophages in the acute phase, leading to diminished fibroblast activation and mitigated peritendinous adhesion. Consequently, this study furnishes a swift RNA editing strategy for macrophages in the inflammatory phase triggered by ROS in tendon injury, along with a pioneering macrophage-targeted carrier proficient in delivering Cas13 into macrophages efficiently.

Synthesis and Characterization of Baicalein-loaded Aquasomes: An In vitro and In silico Perspective for Diabetes Mellitus.

Millions of individuals worldwide suffer from metabolic abnormalities induced by diabetes. Baicalein, a flavonoid, has shown several properties in various treatments with potential properties, including anti-inflammatory, antioxidant, and anti-diabetic properties. Practically, its application is hindered due to low solubility in aqueous media. Overcoming this challenge, aquasomes can offer an effective approach for delivering drugs and bioactive molecules to target various diseases. The study aimed to develop and evaluate baicalein-loaded aquasomes for improving solubility and comparing their antidiabetic properties to acarbose through in silico docking. Baicalein-loaded aquasomes were prepared through a three-step process: core preparation, lactose coating, and drug loading. The evaluation included assessing particle size, drug-excipient interactions, drug entrapment efficiency, loading capacity, in vitro drug release, and the kinetics of drug release. In silico docking and in vitro α-amylase inhibition activity was evaluated to assess the anti-diabetic potential of baicalein. The baicalein-loaded aquasomes were spherical with sizes ranging from 300-400 nm. FTIR analysis indicated no interaction between the components. The formulation exhibited drug entrapment efficiency of 94.04±0 4.01% and drug loading of 17.60 ± 01.03%. Drug release study showed sustained and complete (97.30 ± 02.06 %) release, following first-order kinetics. Docking analysis revealed comparable binding affinity to acarbose, while the α-amylase inhibition assay showed greater inhibition potential of the aquasomes compared to the baicalein solution. Aquasomes offer an alternative approach to conventional delivery methods. The selfassembling characteristics of aquasomes greatly simplify their preparation process, adding to their appeal as a drug delivery system.

Tissue Nanotransfection Silicon Chip and Related Electroporation-Based Technologies for In Vivo Tissue Reprogramming.

Tissue nanotransfection (TNT), a cutting-edge technique of in vivo gene therapy, has gained substantial attention in various applications ranging from in vivo tissue reprogramming in regenerative medicine, and wound healing to cancer treatment. This technique harnesses the advancements in the semiconductor processes, facilitating the integration of conventional transdermal gene delivery methods-nanoelectroporation and microneedle technologies. TNT silicon chips have demonstrated considerable promise in reprogramming fibroblast cells of skin in vivo into vascular or neural cells in preclinical studies to assist in the recovery of injured limbs and damaged brain tissue. More recently, the application of TNT chips has been extended to the area of exosomes, which are vital for intracellular communication to track their functionality during the wound healing process. In this review, we provide an in-depth examination of the design, fabrication, and applications of TNT silicon chips, alongside a critical analysis of the electroporation-based gene transfer mechanisms. Additionally, the review discussed the existing limitations and challenges in the current technique, which may project future trajectories in the landscape of gene therapy. Through this exploration, the review aims to shed light on the prospects of TNT in the broader context of gene therapy and tissue regeneration.

REVOLUTIONIZING PHARMACEUTICALS: A DEEP DIVE INTO SELF NANO EMULSIFYING DRUG DELIVERY SYSTEMS

From nearly a decade’s time, there has been an increased inclination with respect to nanoemulsions owing to their augmented and ameliorated characteristics in comparison to conventional methods of drug delivery. Self-nano-emulsifying drug delivery systems (SNEDDS) have substantiated their effectiveness in enhancing the solubility and bioavailability of poorly soluble substances. These systems, often isotropic mixtures, consist of oils, surfactants, and cosurfactants/cosolvents. They possess the capability to create nanoemulsions or fine oil-in-water (o/w) emulsions with mild stirring and dilution by the water phase along the gastrointestinal tract. This system has proven its worth in enhancing the absorption of lipophilic agents constrained by dissolution rate. SNEDDS are extremely efficacious in improving the oral bioavailability of lipophilic products and is quite promising for managing drugs unapt for oral delivery. Additionally, it's noteworthy that SNEDDS can be formulated into various solid dosage forms suitable for both oral and parenteral administration. This overview incorporates the advancements of SNEDDS' the mechanism involved in its spontaneous formation, its subcategories, composition, approaches employed for formulation, characterization, merits and limitations, and future potential. The review also lays stress on the progress in solid self-emulsifying delivery mechanisms and dosage forms.

Near-infrared controlled release of mesenchymal stem cells secretome from bioprinted graphene-based microbeads for nerve regeneration

 Nerve damage is a prevalent and debilitating condition with limited treatment options. Recent years have seen an increased incidence of neural damage due to factors such as aging populations and traumatic brain injuries. Addressing the urgent need for effective therapies, this study explores the controlled delivery of mesenchymal stem cells (MSCs) secretome, a complex mixture of bioactive factors, which is currently being investigated for its potential in nerve regeneration. The secretome offers significant advantages over stem cells themselves, as it can be more easily characterized and controlled, enabling precise regulation of therapeutic interventions. However, the challenge lies in delivering the secretome specifically to the target anatomical region. To overcome this limitation, we propose a novel approach utilizing near-infrared (NIR) radiation-responsive bioprinted alginate-graphene oxide (AGO) microbeads. Graphene oxide (GO) is a highly biocompatible material with unique properties, including NIR responsiveness, enabling controlled release of therapeutic agents upon NIR exposure. We hypothesized that AGO microbeads could encapsulate MSCs secretome and release it in a controlled manner using NIR radiation. To investigate our hypothesis, controlled damage was induced to hippocampal neurons, and MSCs secretome was encapsulated within AGO microbeads. Subsequently, NIR radiation was applied to trigger the release of the secretome. We compared the efficacy of MSCs secretome with that of astrocytes, which also possess nerve growth and proliferation-promoting capabilities. Our findings demonstrated that the controlled release of MSCs secretome from AGO microbeads through non-invasive NIR radiation significantly promoted the proliferation and regeneration of neurons following nerve injury. AGO microbeads offer multiple advantages over conventional delivery methods, including precise control over the timing, location, and dosage of therapeutic agents. Furthermore, the potential for reduced immunogenicity and tumorigenicity enhances the safety profile of the therapy. Consequently, this study presents a promising avenue for the development of MSC-based therapies for nerve regeneration, with implications for the treatment of various neuropathies and injuries.  

Anti-ricin toxin human neutralizing antibodies and DMAbs protection against ricin toxin poisoning

DNA-encoded monoclonal antibodies (DMAbs) and in vivo expression of antibody therapeutics presents an innovative alternative to conventional delivery methods. Therefore, in order to prevent the lethal dose of ricin toxin (RT) and to avoid human anti-mouse antibody (HAMA) reaction, we developed the human neutralizing antibody 4–4E against RT and constructed DMAb-4–4E. The human neutralizing antibody 4–4E could neutralize RT in vitro and in vivo, while the mice in RT group all died. Using intramuscular electroporation (IM EP), antibodies were rapidly expressed in vivo within 7 days and were enriched in intestine and gastrocnemius muscle mostly. Besides, we found that DMAbs have shown a broad protective efficacy of RT poisoning prophylaxis. Driven by plasmids for IgG expression, mice were survived and the blood glucose level of mice in DMAb-IgG group returned to normal at 72 h post RT challenge, and the RT group died within 48 h. Furthermore, hindrance of protein disulfide isomerase (PDI) and accumulation of RT in endosomes were found in IgG-protected cells, revealing the possible mechanism of neutralization details. These data support the further study of RT-neutralizing monoclonal antibodies (mAbs) in the development.

Creating an evidence-based economic model for prefilled parenteral medication delivery in the hospital setting

ObjectivesPrefilled syringes (PFS) may offer clinical and economic advantages over conventional parenteral medication delivery methods (vials and ampoules). The benefits of converting from vials and ampoules to PFS have been...

Challenges of Glycemic Control in People With Diabetes and Advanced Kidney Disease and the Potential of Automated Insulin Delivery.

Diabetes is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease in the world. It is known that maintaining optimal glycemic control can slow the progression of CKD. However, the failing kidney impacts glucose and insulin metabolism and contributes to increased glucose variability. Conventional methods of insulin delivery are not well equipped to adapt to this increased glycemic lability. Automated insulin delivery (AID) has been established as an effective treatment in patients with type 1 diabetes mellitus, and there is emerging evidence for their use in type 2 diabetes mellitus. However, few studies have examined their role in diabetes with concurrent advanced CKD. We discuss the potential benefits and challenges of AID use in patients with diabetes and advanced CKD, including those on dialysis.

Cylindrical lens configuration for optimizing light delivery in a curvilinear endocavity photoacoustic imaging system.

Curvilinear endocavity ultrasound images capture a wide field of view with a miniature probe. In adapting photoacoustic imaging (PAI) to work with such ultrasound systems, light delivery is challenged by the trade-off between image quality and laser safety concerns. Here, we present two novel, to the best of our knowledge, designs based on cylindrical lenses that are optimized for transvaginal PAI B-scan imaging. Our simulation and experimental results demonstrate that, compared to conventional light delivery methods for PAI imaging, the proposed designs are safer for higher pulse energies and provide deeper imaging and a wider lateral field of view. The proposed designs could also improve the performance of endoscopic co-registered ultrasound/photoacoustic imaging in other clinical applications.

Sustainable crowdsourced delivery: A study of technological, health, value, and trust antecedents of consumer loyalty

Crowdsourced delivery has various advantages over conventional delivery methods, including a decrease in emissions and road congestion. These benefits grow as consumer loyalty is established due to network externalities. This study seeks to identify the factors influencing customer loyalty to crowdsourced delivery through the unified theory of acceptance and use of technology, the health belief model, the perceived value theory, and the trust theory. First, a questionnaire was administered to 500 respondents in Singapore, and the data was analyzed using structural equation modeling. The findings show that technology and health belief constructs have direct impacts on the perceived value of crowdsourced delivery, while perceived value has direct and indirect effects on consumer loyalty through trust. Overall, this study contributes to the literature theoretically and practically by developing a paradigm for understanding the growth of customer loyalty to crowdsourced delivery from the perspectives of consumers and health beliefs. It also offers operators and policymakers concrete areas for improvement in resource allocation, security, and marketing to increase overall consumer loyalty to crowdsourced delivery.

Recent Trends in Phytosome Nanocarriers for Improved Bioavailability and Uptake of Herbal Drugs

Phytopharmaceuticals or herbal drugs have a significant therapeutic impact on healthcare systems. Though herbal extracts and their active constituents show excellent pharmacological in vitro effects, they still have indigent in vivo biological effects because of their considerable molecular weight and low lipid solubility, leading to low systemic availability. Phytosome is a novel approach for overcoming the drawbacks of conventional delivery methods of herbal actives. The phospholipids, mainly phosphatidylcholine, form a bond with herbal extracts or actives, forming a herb-lipid complex. The encapsulation of herbal actives with phospholipid allows an effective tool for the delivery to the affected area with enhanced pharmacological effect. Moreover, the amphiphilic nature of the phospholipid provides a good hydrophilic-lipophilic balance, thereby improving a better dissolution profile in the lipid-rich membranes of the gastrointestinal tract. This review focuses on the various phytosome nanocarriers to improve herbal medication bioavailability and uptake—recent trends in their industrial applicability, and applications in clinical management for various diseases, including other challenges.

Macromolecular crowding and decellularization method increase the growth factor binding potential of cell-secreted extracellular matrices.

Recombinant growth factors are used in tissue engineering to stimulate cell proliferation, migration, and differentiation. Conventional methods of growth factor delivery for therapeutic applications employ large amounts of these bioactive cues. Effective, localized growth factor release is essential to reduce the required dose and potential deleterious effects. The endogenous extracellular matrix (ECM) sequesters native growth factors through its negatively charged sulfated glycosaminoglycans. Mesenchymal stromal cells secrete an instructive extracellular matrix that can be tuned by varying culture and decellularization methods. In this study, mesenchymal stromal cell-secreted extracellular matrix was modified using λ-carrageenan as a macromolecular crowding (MMC) agent and decellularized with DNase as an alternative to previous decellularized extracellular matrices (dECM) to improve growth factor retention. Macromolecular crowding decellularized extracellular matrix contained 7.7-fold more sulfated glycosaminoglycans and 11.7-fold more total protein than decellularized extracellular matrix, with no significant difference in residual DNA. Endogenous BMP-2 was retained in macromolecular crowding decellularized extracellular matrix, whereas BMP-2 was not detected in other extracellular matrices. When implanted in a murine muscle pouch, we observed increased mineralized tissue formation with BMP-2-adsorbed macromolecular crowding decellularized extracellular matrix in vivo compared to conventional decellularized extracellular matrix. This study demonstrates the importance of decellularization method to retain endogenous sulfated glycosaminoglycans in decellularized extracellular matrix and highlights the utility of macromolecular crowding to upregulate sulfated glycosaminoglycan content. This platform has the potential to aid in the delivery of lower doses of BMP-2 or other heparin-binding growth factors in a tunable manner.

NATURE OF NANOPARTICLES AND THEIR APPLICATIONS IN TARGETED DRUG DELIVERY

Nanotechnology is a rapidly growing field and has secured a prominent rank in medicinal field. They find applications in cancer therapy, cell bio-imaging, in treatment of neurodegenerative diseases, in targeted drug delivery at cell or tissue level and also in the regeneration of tissues and different organs. NPs like liposomes and dendrimers are widely used as nanocarriers. They can be successfully employed in drug delivery due to their specific properties like bioavailability, their biocompatibility and accumulation only at the specific target site without harming or affecting other non target tissues. They are superior in targeted drug delivery as compared to the conventional methods of drug delivery. Nanoparticles (NPs) are synthesized by various techniques and approaches.

Manufacturing of a Transdermal Patch in 3D Printing.

Diabetes mellitus is an endocrine disorder that affects glucose metabolism, making the body unable to effectively use the insulin it produces. Transdermal drug delivery (TDD) has attracted strong interest from researchers, as it allows minimally invasive and painless insulin administration, showing advantages over conventional delivery methods. Systems composed of microneedles (MNs) assembled in a transdermal patch provide a unique route of administration, which is innovative with promising results. This paper presents the design of a transdermal patch composed of 25 microneedles manufactured with 3D printing by stereolithography with a class 1 biocompatible resin and a printing angle of 0°. Finite element analysis with ANSYS software is used to obtain the mechanical behavior of the microneedle (MN). The values obtained through the analysis were: a Von Misses stress of 18.057 MPa, a maximum deformation of 2.179×10-3, and a safety factor of 4. Following this, through a flow simulation, we find that a pressure of 1.084 Pa and a fluid velocity of 4.800 ms were necessary to ensure a volumetric flow magnitude of 4.447×10-5cm3s. Furthermore, the parameters found in this work are of great importance for the future implementation of a transdermal drug delivery device.

Desires and Attitudes towards Telepharmacy Medicine Delivery.

The COVID-19 pandemic has limited healthcare services for patients with non-communicable diseases (NCDs). Hospital pharmacy departments in Thailand apply a new normal pharmacy service known as “telepharmacy” to serve remote pharmacy practice and deliver medication to patients. Current knowledge clearly shows the benefit of each medicine delivery method, but the study of patient’s desires and attitudes towards all drug delivery methods is still limited. To fill the gap, this study aims to investigate desires and attitudes about drug delivery methods among Thai patients living with NCDs who need regular and continuous care. The sample was included by accidentally randomized technique at NCD clinics of the southern Thailand tertiary care hospital. Data were collected between January and March 2021 by a questionnaire that contained three sections: the currently received medicine delivery method, the desires and attitudes about the medicine delivery system, and patients’ demographic information. The majority of patients were women aged 60 years who earned less than 10,000 THB (263.85 USD), were enrolled in the Civil Servant Medical Benefit Scheme (CSMBS), lived 0–15 km from the hospital, living with hypertension, had 1–4 prescribed medications, visited the doctor every 3 months, and received the conventional drug delivery method. The result showed that only the subdistrict health promotion hospital (SHPH) medicine delivery method was at a high level of desire, while the rest including conventional, drug store, postal pharmacy, and drive-thru medicine delivery methods were at medium. Attitudes toward the quality of medicine delivery methods consisted of five dimensions: confidence, timeliness, reliability, empathy, and facilities. Thai NCD patients had positive attitudes toward SHPH and drug store medicine delivery methods that could be seen from the high level of attitude score across all dimensions, while postal pharmacy and drive-thru delivery methods received medium-level attitude scores across all five dimensions.

THE LEGAL PERSPECTIVES OF THE DOCTRINE OF NAVIGABILITY OF AIRSPACE FOR COMMERCIAL UNMANNED AERIAL VEHICLES (UAVs) IN SHIPPING AND DELIVERY

The emergence of the Covid-19 pandemic has had a massive social and economic impact all over the world. The conventional methods of logistics, shipping, and delivery of goods are crucial in the economic chains. The use of commercial unmanned aerial vehicles (UAVs) for shipping and delivery has been viewed as an innovative approach and business strategy for the logistics company. Commercial UAVs in shipping and delivery might be a novel and effective delivery technique in logistic services, especially for small parcels, and could be extended to medical supplies. However, due to the rigidity of laws and regulations in providing the right of way and other infrastructures to commercial UAVs, UAVs in shipping and delivery appear to be unwelcome in Malaysia. This article is based on doctrinal research and seeks to analyze the regulatory pattern of the doctrine of navigability of low-altitude airspace for the shipping and delivery of UAVs in Malaysia and other selected countries. Moreover, this article also further highlights the various secondary sources of laws from the various authors to view their standing on the navigability concept of UAVs in shipping and delivery. This article recommends the segregation of the low-altitude navigable airspace for UAVs to resolve the conflict of interest between the proprietor’s airspace and the navigable airspace of manned aircraft and further suggests other infrastructures for the expansion of UAVs in the logistics sector.

Olfactory Drug Aerosol Delivery with Acoustic Radiation.

Nose-to-brain (N2B) drug delivery is a new approach to neurological disorder therapy as medications can bypass the blood-brain barrier and directly enter the brain. However, the delivery efficiency to the olfactory region using the conventional delivery method is impractically low because of the region’s secluded position in a convoluted nasal cavity. In this study, the acoustic radiation force was explored as an N2B delivery alternative in a wide frequency range of 10–100,000 Hz at an increment of 50 Hz. Numerical simulations of the particle deposition in the olfactory region of four nasal configurations were performed using COMSOL. Frequency analysis of the nasal cavities revealed that eigenfrequencies were often associated with a specific region with narrow passages and some eigenfrequencies exhibited an amendable pressure field to the olfactory region. Transient particle tracking was conducted with an acoustic inlet at 1 Pa, and a frequency spectrum of 10–100,000 Hz was imposed on the airflow, which carried the particles with acoustic radiation forces. It was observed that by increasing the pulsating wave frequency at the nostrils, the olfactory delivery efficiency reached a maximum in the range 11–15 kHz and decreased after that. The correlation of the olfactory delivery efficiency and instantaneous values of other parameters such as acoustic velocity and pressure in the frequency domain was examined.