The Use of Nanoneedles in Drug Delivery: an Overview of Recent Trends and Applications.

Nanoneedles (NN) are growing rapidly as a means of navigating biological membranes and delivering therapeutics intracellularly. Nanoneedle arrays (NNA) are among the most potential resources to achieve therapeutic effects by administration of drugs through the skin. Although this is based on well-established approaches, its implementations are rapidly developing as an important pharmaceutical and biological research phenomenon. This study intends to provide a broad overview of current NNA research, with an emphasis on existing approaches, applications, and types of compounds released by these systems. A nanoneedle-based delivery device with great spatial and temporal accuracy, minimal interference, and low toxicity could transfer biomolecules into living organisms. Due to its vast potential, NN has been widely used as a capable transportation system of many therapeutic active substances, from cancer therapy, vaccine delivery, cosmetics, and bio-sensing nanocarrier drugs to genes. The use of nanoneedles for drug delivery offers new opportunities for the rapid, targeted, and exact administration of biomolecules into cell membranes for high-resolution research of biological systems, and it can treat a wide range of biological challenges. As a result, the literature has analyzed existing patents to emphasize the status of NNA in biological applications.

Subconjunctival therapy by cubic liquid crystalline nanoparticles to deliver Triamcinolone acetonide for the management of diabetic Retinopathy: In vivo evidences.

The expression of inflammatory markers and vascular endothelial growth factor (VEGF) was found to be upregulated in various posterior ocular disorders, including diabetic retinopathy (DR). Effective delivery of therapeutic agents to the retina poses a significant challenge in ophthalmic drug delivery due to biological ocular barriers. Triamcinolone acetonide (TA) was selected as the model corticosteroid drug targeting cytokines and VEGF in DR. However, despite TA's low molecular weight and hydrophobicity, which enable it to bypass the conjunctival epithelial barrier, it doesn't efficiently exert its effect at the target site. Nanocarriers have emerged as a solution to enhance drug delivery to the retina and improve bioavailability. This study aimed to compare the effects of Triamcinolone-loaded cubic liquid crystalline nanoparticles (TA-cubic LCNPs) and TA-Suspension in an experimental DR model administered via the subconjunctival (SCJ) route. The results demonstrated that TA-cubic LCNPs enhanced TA periocular delivery efficacy by reducing inflammatory and VEGF markers through the advanced glycation end products (AGE)/protein kinase C pathway. They were identified as promising nano-carriers, exhibiting potential for targeted delivery to the retina.

A Dual Therapy of Nanostructured Lipid Carrier Loaded with Teriflunomide-A Dihydro-Orotate Dehydrogenase Inhibitor and an miR-155-Antagomir in Cuprizone-Induced C57BL/6J Mouse.

The effective treatment of central nervous system (CNS) disorders such as multiple sclerosis (MS) has been challenging due to the limited ability of therapeutic agents to cross the blood-brain barrier (BBB). In this study, we investigated the potential of nanocarrier systems to deliver miR-155-antagomir-teriflunomide (TEF) dual therapy to the brain via intranasal (IN) administration to manage MS-associated neurodegeneration and demyelination. Our results showed that the combinatorial therapy of miR-155-antagomir and TEF loaded in nanostructured lipid carriers (NLCs) significantly increased brain concentration and improved targeting potential. The novelty of this study lies in the use of a combinatorial therapy approach of miR-155-antagomir and TEF loaded in NLCs. This is a significant finding, as the effective delivery of therapeutic molecules to the CNS has been a challenge in treating neurodegenerative disorders. Additionally, this study sheds light on the potential use of RNA-targeting therapies in personalized medicine, which could revolutionize the way CNS disorders are managed. Furthermore, our findings suggest that nanocarrier-loaded therapeutic agents have great potential for safe and economical delivery in treating CNS disorders. Our study provides novel insights into the effective delivery of therapeutic molecules via the IN route for managing neurodegenerative disorders. In particular, our results demonstrate the potential of delivering miRNA and TEF via the intranasal route using the NLC system. We also demonstrate that the long-term use of RNA-targeting therapies could be a promising tool in personalized medicine. Importantly, using a cuprizone-induced animal model, our study also investigated the effects of TEF-miR155-antagomir-loaded NLCs on demyelination and axonal damage. Following six weeks of treatment, the TEF-miR155-antagomir-loaded NLCs potentially lowered the demyelination and enhanced the bioavailability of the loaded therapeutic molecules. Our study is a paradigm shift in delivering miRNAs and TEF via the intranasal route and highlights the potential of this approach for managing neurodegenerative disorders. In conclusion, our study provides critical insights into the effective delivery of therapeutic molecules via the IN route for managing CNS disorders, and especially MS. Our findings have significant implications for the future development of nanocarrier-based therapies and personalized medicine. Our results provide a strong foundation for further studies and the potential to develop safe and economic therapeutics for CNS disorders.

Novel Gels: An Emerging Approach for Delivering of Therapeutic Molecules and Recent Trends.

Gels are semisolid, homogeneous systems with continuous or discrete therapeutic molecules in a suitable lipophilic or hydrophilic three-dimensional network base. Innovative gel systems possess multipurpose applications in cosmetics, food, pharmaceuticals, biotechnology, and so forth. Formulating a gel-based delivery system is simple and the delivery system enables the release of loaded therapeutic molecules. Furthermore, it facilitates the delivery of molecules via various routes as these gel-based systems offer proximal surface contact between a loaded therapeutic molecule and an absorption site. In the past decade, researchers have potentially explored and established a significant understanding of gel-based delivery systems for drug delivery. Subsequently, they have enabled the prospects of developing novel gel-based systems that illicit drug release by specific biological or external stimuli, such as temperature, pH, enzymes, ultrasound, antigens, etc. These systems are considered smart gels for their broad applications. This review reflects the significant role of advanced gel-based delivery systems for various therapeutic benefits. This detailed discussion is focused on strategies for the formulation of different novel gel-based systems, as well as it highlights the current research trends of these systems and patented technologies.