Patenting drug delivery technology: tips for formulating practical and effective patent portfolio.

The Second Annual Ophthalmic Drug Development and Delivery Summit was held on 19 – 20 September 2006 in San Diego, CA, US. The 2-day symposium, having a highly focused theme, was packed with cutting-edge science, insightful overviews and networking opportunities. With a total of 11 recognized specialists presenting reviews and recent results in the advancement of ocular drug development and delivery, the invited expert speaking faculty presented the latest preclinical and clinical developments in novel ophthalmic therapies and drug delivery technology. The talks included various case studies from primary investigators and pharmaceutical companies touching upon key topics: updates on current clinical trials, study design issues, sustained delivery to the eye, views of the vitreous space as a drug reservoir, new developments in dry and wet age-related macular degeneration and diabetic retinopathy, formulation for optimal drug delivery, differences and similarities in developing drugs for the eye compared with other targets, pharmacokinetics, novel ocular delivery methods and devices, delivery of proteins and peptides, focal drug delivery, non-invasive drug delivery to the eye, neuroprotection challenges, in vitro and in vivo models for glaucoma and angiogenesis for early efficacy estimation, and toxicology. Overall, the 2-day annual symposium continues to grow as an efficient platform for fostering discussion on a range of scientific topics and challenges and avenues for building collaborative partnerships in ophthalmic drug development.

Passive topical administration of nucleic acid drugs and vaccines is a desirable goal for patient-friendly manipulation of target cells in the skin. However, two major delivery challenges that have impeded development are 1) penetrating the stratum corneum, and 2) avoiding endosomal entrapment and degradation. GeneSegues has developed a novel drug delivery technology, sub-50 nanometer (s50) crystallized capsules, for intact delivery of nucleic acids to intracellular sites in target cells. s50 capsules are directed to specific tissue and cells by formulating appropriate targeting proteins, peptides or antibody ligands as the crystallized capsule shell. The novel size and structure of s50 capsules allows for efficient penetration of the stratum corneum and, by co-opting the non-endosomal pathway referred to as “lipid rafts”, intact delivery of nucleic acid cargo to the nucleus and cytoplasm of the target cell. Here we show in pilot studies using pig dermis organ culture as an established and relevant model for human skin, transcutaneous passage of plasmid-bearing s50 capsules with cell-specific targeting. In these studies, we compared fibronectin, hyaluronan and tenascin as shell targeting components. We extended these studies of passive cutaneous delivery, using plasmid-bearing, fibronectin-coated s50 capsules, to in vivo timecourse studies in murine paws where stratum corneum layers in footpads are approximately 50 um thick, demonstrating uniform transfection of underlying basal keratinocytes. In a further extension, using hyaluronan-coated s50 capsules together with a novel adjuvant, we demonstrate a functional response to model antigen in studies of passive topical DNA vaccine adminstration in weanling pigs. Skin is a powerful immune organ, not conveniently addressed by current methods of vaccine administration, e.g., injection, gene gun, or electroporation. We found improvement in mucosal and cell-mediated immune responses, relative to intradermal protein antigen injection that was biased towards distal and draining nodal lymphoctyes, demonstrating a functional response in a clinically relevant model to topical administration of nucleic acids using s50 capsules. We expect that with further characterization, these studies may provide a solid framework for further development of s50-mediated cutaneous delivery of nucleic acid drugs and vaccines. Grant acknowledgments: NIH R43 CA119556, R43 AI60268

135P - Can we improve patient selection for phase I clinical trials (phI1) based on immuno-oncology score prognostic index (VIO)?

Novel Polyaminolipids Enhance the Cellular Uptake of Oligonucleotides

The new method, known as nanostructured lipid carrier (NLC) in drug delivery systems, has the potential to increase therapeutic efficacy, stability, and bioavailability. This systematic literature review aimed to provide a detailed summary of NLC technology in drug delivery systems, including routes of administration, preparation methods, characterization, and utilization for the delivery of anti-aging active ingredients in cosmetics. To collect scholarly articles on NLCs, we employed a systematic search method using Google Scholar and PubMed. After the screening process, 53 pertinent papers out of 102 articles were chosen for descriptive analysis. NLC exhibit significant promise in many drug delivery applications, including oral, topical, parenteral, and transmucosal routes, with many benefits, including improved bioavailability, stability, and drug penetration through the skin, cornea, and brain. Moreover, NLC technology has been effectively applied for the administration of drugs, including anti-aging drugs. Topical anti-aging preparations generally use synthetic or natural active ingredients. However, synthetic ingredients are often less stable and can irritate skin. NLC can protect and control the release of active ingredients, thereby reducing the risk of irritation. NLC can also improve the penetration of active ingredients into the deeper layers of the skin, allowing it to reach the dermis layer, which is responsible for most skin aging. The efficient absorption capacity of NLC technology in topical preparations presents new opportunities for anti-aging cosmetic product development owing to its effectiveness in skin penetration. Keywords: Nanostructured Lipid Carrier (NLC), drug delivery system, drug penetration, anti-aging

Osteoarthritis (OA) is one of the most common joint degenerative diseases in the world. At present, the management of OA depends on the lifestyle modification and joint replacement surgery, with the lifespan of prosthesis quite limited yet. Effective drug treatment of OA is essential. However, the current drugs, such as the non-steroidal anti-inflammatory drugs and acetaminophen, as well as glucosamine, chondroitin sulfate, hyaluronic acid, are accompanied by obvious side effects, with the therapeutic efficacy to be enhanced. Recently, novel reagents such as IL-1 antagonists and nerve growth factor inhibitors have entered clinical trials. Moreover, increasing evidence demonstrated that active ingredients of natural plants have great potential for treating OA. Meanwhile, the use of novel drug delivery strategies may overcome the shortcomings of conventional preparations and enhance the bioavailability of drugs, as well as decrease the side effects significantly. This review therefore summarizes the pathological mechanisms, management strategies, and research progress in the drug molecules including the newly identified active ingredient derived from medicinal plants for OA therapy, with the drug delivery technologies also summarized, with the expectation to provide the summary and outlook for developing the next generation of drugs and preparations for OA therapy.

Nucleic acid therapeutics have emerged as a powerful method for treatment of many diseases. However, the challenge lies in safe and efficient delivery of nucleic acids to their target site, as they need to cross various extracellular and intracellular barriers. Mammalian viruses have initially been favored for delivery of nucleic acid therapeutics, but safety concerns regarding their immunogenicity and potential of integration have fueled the search for alternative delivery strategies. For example, chemistry and bioengineering have led to advances in the use of nonviral vectors composed of lipids and other polymers; nevertheless, the synthetic systems often do not match the efficiency achieved using the biological systems. More recently, researchers have turned toward the development of plant viruses and bacteriophages and virus-like particles as an alternative or complementary approach. These systems unite the properties of both the viral and nonviral systems and as such are a new exciting avenue toward nucleic acid delivery. This review highlights the benefits of plant viral and bacteriophage delivery of nucleic acids and provides a summary of the current progress in research in this field. WIREs Nanomed Nanobiotechnol 2018, 10:e1487. doi: 10.1002/wnan.1487 This article is categorized under: Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

Microfluidic technologies have become a highly effective platform for the precise and reproducible production of nanovesicles used in drug and nucleic acid delivery. One of their key advantages lies in the one-step assembly of multidrug delivery nanovesicles, which improves batch-to-batch reproducibility by minimizing the intermediate steps typically required in conventional methods. These steps often involve complex hydrophobic and electrostatic interactions, leading to variability in the nanovesicle composition and performance. Microfluidic systems streamline the encapsulation of diverse therapeutic agents, including hydrophilic nucleic acids, proteins, and both hydrophobic and hydrophilic small molecules, within a single chip, ensuring a more consistent production process. This capability enables the codelivery of multiple drugs targeting different disease pathways, which is particularly valuable in reducing the risk of drug resistance. Despite the promise of nanovesicles for nucleic acid delivery, their clinical translation has been hindered by safety concerns, particularly cytotoxicity, which has overshadowed efforts to improve in vivo stability and delivery efficiency. Positively charged nanovesicles, commonly used to encapsulate negatively charged nucleic acids, tend to exhibit significant cytotoxicity. To address this, charge-shifting materials that respond to pH changes or surface modifications have been proposed as promising strategies. Shifting the surface charge from positive to neutral or negative at physiological pH can reduce the cytotoxicity, enhancing the clinical feasibility of these nanovesicle-based therapies. Microfluidic platforms offer precise control over key nanovesicle properties, including particle size, rigidity, morphology, and encapsulation efficiency. Particle size is relatively easy to adjust by controlling flow rates within microfluidic channels, with higher flow rates generally producing smaller particles. However, continuous tuning of the particle rigidity remains challenging. By manipulation of the interfacial water layer between hydrophobic and amphiphilic components during nanoparticle formation, future designs may achieve greater control over rigidity, which is critical for improving cellular uptake and biodistribution. While shape tuning using microfluidic chips has not yet been fully explored in biomedical applications, advances in materials science may enable this aspect in the future, offering further customization of the nanovesicle properties. The integration of nanovesicle assembly and surface modification within a single microfluidic platform presents challenges due to the differing speeds of these processes. Nanovesicle assembly is typically rapid, whereas surface modifications, such as those involving functional biomolecules, occur more slowly and often require purification steps. Recent advances, such as rotary valve designs and single-axis camshaft mechanisms, offer precise control over flow mixing at different stages of the process, allowing for the automation of nanovesicle assembly and surface modification, thereby improving batch-to-batch reproducibility. In conclusion, microfluidic technologies represent a promising approach for the development of multifunctional nanovesicles with the potential to address key challenges in drug delivery and precision medicine. While obstacles related to cytotoxicity, scalability, and reproducibility remain, innovations in chip design, materials, and automation are paving the way for broader application in clinical settings. Future research, potentially incorporating machine learning, could further optimize the relationship between nanovesicle properties and biological outcomes, advancing the use of microfluidic technologies for therapeutic delivery.

Bacterial ghosts – biological particles as delivery systems for antigens, nucleic acids and drugs

Tiny titans- unravelling the potential of polysaccharides and proteins based dissolving microneedles in drug delivery and theranostics: A comprehensive review

Plant-based foods contain flavonoids, belonging to the polyphenols class. The phytochemical and phyto-pharmacological sciences advancement has enabled composition elucidation and biological activities of various medicinal plant products. The efficacy of medicinal plants can be measured on the basis of bio-active constituents they comprise. Flavonoid is one of the classes among the bio-active constituents that are hydrophilic in nature. They have low bioavailability and efficacy due to low absorption, as they cannot cross cells lipid membrane due to larger molecular size. A variety of novel drug delivery systems have been developed for polyphenolic compounds to enhance the relative bioavailability. However, if novel drug delivery technology is applied, it may reduce the adverse effects and increase the efficacy of several herbs and their compounds. Herbal medicines were not encouraged for novel formulations development for a long time due to lack of scientific justification and processing difficulties, such as individual drug components identification, extraction and standardization in complex poly-herbal systems. However, advance phytopharmaceutical research can reduce the scientific thirst (e.g, pharmacokinetics determination, mechanism of action, the accurate dose required, site of action etc.) for herbal medicines to be incorporated in novel drug delivery systems, such as nanoparticles (NPs), liposomes, matrix systems, and micro-emulsions (-E) etc. by improving activity by reducing the side effects and required dose. Various drug delivery technologies have been summarized in this chapter which can be used for flavonoids loaded polymeric drug delivery systems.

In recent years, novel drug delivery systems (NDDS) have been recognized as an attractive niche for the pharmaceutical and health industry. Among various NDDS, osmotic pumps have matured from their use with laboratory animals to the most reliable controlled release systems for humans. Osmotically controlled drug delivery systems use osmotic pressure for controlled delivery of active agent(s). Drug delivery from these systems, to a large extent, is independent of the physiological factors of the gastrointestinal tract. Because of their unique advantages over other types of dosage forms, osmotic pumps form a class of their own among the various drug delivery technologies, and a variety of products based on this technology are available on the market. This article is a review of different types of osmotic pumps and their role in drug delivery.

Objectives: This review provides a detailed review of the treatment of obesity with natural products that are formulated as phytosomes. When novel drug delivery technology is used instead of traditional drug delivery in herbal medicine, side effects are reduced while safety and efficacy are improved.This article provides information about obesity along with its treatment and with special emphasis on phytosomes, their preparation and evaluation along with their application in obesity. Methods: A comprehensive search of electronic databases such as Medline, Embase, Cochrane Library, Google, and Google Patents was carried out. Results: This review explains the details of research done on phytosomes with special reference to anti-obesity drugs. Still, there is a need to formulate anti-obesity herbal drugs as phytosomes to get better bioavailability, and fewer side effects. This phytosomal drug delivery approach may resolve the problems associated with conventional drug delivery. Conclusion: Integrating herbal medicine with novel drug delivery systems such as phytosomes to combat obesity has a significant scope and importance.

Nanomedicine-based combination anti-cancer therapy between nucleic acids and anti-cancer Nano drugs in covalent Nano drugs delivery systems for selective imaging and treatment of human brain tumors using hyaluronic acid, alguronic acid and sodium hyaluronate (Figures 1 and 2) as anti-cancer Nano drugs and nucleic acids delivery under synchrotron radiation has been explored as an alternative approach to the synthesis of electronically and optically active polymers with several advantages1-33. Horseradish Peroxidase (HRP) catalyzes the decomposition of Hydrogen peroxide (H2O2) at the expense of aromatic proton donors. Horseradish Peroxidase (HRP) is a Fe containing porphyrin-type structure. In previous works, we synthesized hyaluronic acid, alguronic acid and sodium hyaluronate, enzymatically1-33. The results of enzymatic polymerization were different from chemical and electrochemical polymerization of hyaluronic acid, alguronic acid and sodium hyaluronate that reported previously1-33. In this editorial, we reported the enzymatic copolymerization of aniline and hyaluronic acid, alguronic acid and sodium hyaluronate with Horseradish Peroxidase (HRP) in the presence of Sulfonated Polystyrene (SPS) as a template.

that could enable an epidermal targeting effect."