The Release Kinetics of Melatonin from Innovative Dosage Forms: The Role of the Fractal Geometry of the “Vehicle”

Melatonin (N-acetyl-5-methoxytryptamine) is an antioxidant active pharmaceutical ingredient with numerous applications as medicine and nutraceutical. Melatonin, a hormone synthesized by the pineal gland, has a significant role in the regulation of the circadian biological clock. The aim of this chapter is to present the conventional solid and liquid forms (i.e., tables, capsules, suspensions, etc.) and the nanoformulations (i.e., liposomes, niosomes, polymeric nanoparticles, chitosomes, calcium alginate beads, etc.) of melatonin and to give special attention to its release kinetics from the pharmaceutical vehicle. These systems have been designed and developed as platforms for the delivery and release of melatonin. In all cases, the controlled release of melatonin is the main goal of its loading into drug delivery platforms. Fractal analysis is a mathematical tool to quantify nature and physical systems’ complexity. These systems have been characterized as fractal objects, due to their fractional dimensions. In this chapter, we are probing the interrelationship between the fractal dimension of pharmaceutical vehicle and the release profile of melatonin. Several examples will be given in order to understand in depth the reason of controlled-release profile of melatonin and its added value for the development of a new medicine and/or nutraceutical

Advanced nanocarriers for an antitumor peptide

In this work, tigapotide (PCK3145) was incorporated into novel nanocarriers based on polymeric, lipidic and dendrimeric components, in order to maximize the advantages of the drug delivery process and possibly its biological properties. PCK3145 was incorporated into lipidic nanocarriers composed of Eggphosphatidylcholine (EggPC) and dipalmytoylphosphatidylcholine (DPPC) (EggPC:PCK3145 and DPPC:PCK3145, 9:0.2 molar ratio), into cationic liposomes composed of EggPC:SA:PCK3145 and DPPC:SA:PCK3145 (9:1:0.2 molar ratio) into complexes with the block polyelectrolyte (quaternized poly[3,5bis(dimethylaminomethylene)hydroxystyrene]-b-poly(ethylene oxide) (QNPHOSEO) and finally into dendrimeric structures (i.e. PAMAM G4) . Light scattering techniques are used in order to examine the size, the size distribution and the z-potential of the nanocarriers in aqueous and biological media. Fluorescence spectroscopy was utilized in an attempt to extract information on the internal nanostructure and microenvironment of polyelectrolyte/PCK3145 aggregates. Therefore, these studies could be a rational roadmap for producing various effective nanocarriers in order to ameliorate the pharmacokinetic behavior and safety issues of antitumor and anticancer biomolecules

Complexation of cationic-neutral block polyelectrolyte with insulin and in vitro release studies

Insulin (INS) was incorporated into complexes with the block polyelectrolyte quaternized poly[3,5-bis(dimethylaminomethylene)hydroxystyrene]-b-poly(ethyleneoxide) (QNPHOSEO), which is a cationic-neutral block polyelectrolyte. Light scattering techniques are used in order to examine the size, the size distribution and the ζ-potential of the nanocarriers in aqueous and biological media, which are found to depend on the ratio of the components and the physicochemical parameters during and after complex preparation. Circular dichroism and infrared spectroscopy, employed to investigate the structure of the complexed INS, show no alteration of protein structure after complexation. In vitro release profiles of the entrapped protein are found to depend on the ratio of the components and the solution conditions used during preparation of the complexes

Insulin/Poly(ethylene glycol)-block-poly(L-lysine) Complexes: Physicochemical Properties and Protein Encapsulation

Insulin (INS) was encapsulated into complexes with poly(ethylene glycol)-block poly(L-lysine) (PEG-b-PLys), which is a polypeptide-based block copolymer (a neutral-cationic block polyelectrolyte). These macromolecules can encapsulate INS molecules in aqueous conditions via electrostatic interactions. Light scattering techniques are used in order to examine the complexation process of the hybrid nanoparticles in a gamut of buffers, as a function of protein concnetration. The physicochemical and structural characteristics of the complexes depend on the ionic strength of the aqueous medium, while the concentration of PEG-b-PLys was constant through the series of solutions. As INS concentration increased each polyelectrolyte chain interacts with an increasing number of INS molecules, the degree of charge neutralization becomes higher and the size distribution of the complexes decreased also, especially at the highest ionic strength. The size/structure of complexes diluted in biological medium indicated that the copolymer imparts stealth properties and colloidal and biological stability to the complexes, which could in turn affect the clearance properties in vivo. Therefore, these studies could be a rational roadmap for designing the optimum complexes/effective nanocarriers for proteins and peptides

Chimeric Stimuli-Responsive Liposomes as Nanocarriers for the Delivery of the Anti-Glioma Agent TRAM-34

Nanocarriers are delivery platforms of drugs, peptides, nucleic acids and other therapeutic molecules that are indicated for severe human diseases. Gliomas are the most frequent type of brain tumor, with glioblastoma being the most common and malignant type. The current state of glioma treatment requires innovative approaches that will lead to efficient and safe therapies. Advanced nanosystems and stimuli-responsive materials are available and well-studied technologies that may contribute to this effort. The present study deals with the development of functional chimeric nanocarriers composed of a phospholipid and a diblock copolymer, for the incorporation, delivery and pH-responsive release of the antiglioma agent TRAM-34 inside glioblastoma cells. Nanocarrier analysis included light scattering, protein incubation and electron microscopy, and fluorescence anisotropy and thermal analysis techniques were also applied. Biological assays were carried out in order to evaluate the nanocarrier nanotoxicity in vitro and in vivo, as well as to evaluate antiglioma activity. The nanosystems were able to successfully manifest functional properties under pH conditions, and their biocompatibility and cellular internalization were also evident. The chimeric nanoplatforms presented herein have shown promise for biomedical applications so far and should be further studied in terms of their ability to deliver TRAM-34 and other therapeutic molecules to glioblastoma cells

Promising Nanotechnology Approaches in Treatment of Autoimmune Diseases of Central Nervous System

Multiple sclerosis (MS) is a chronic, autoimmune, neurodegenerative disease of the central nervous system (CNS) that yields to neuronal axon damage, demyelization, and paralysis. Although several drugs were designed for the treatment of MS, with some of them being approved in the last few decades, the complete remission and the treatment of progressive forms still remain a matter of debate and a medical challenge. Nanotechnology provides a variety of promising therapeutic tools that can be applied for the treatment of MS, overcoming the barriers and the limitations of the already existing immunosuppressive and biological therapies. In the present review, we explore literature case studies on the development of drug delivery nanosystems for the targeted delivery of MS drugs in the pathological tissues of the CNS, providing high bioavailability and enhanced therapeutic efficiency, as well as nanosystems for the delivery of agents to facilitate efficient remyelination. Moreover, we present examples of tolerance-inducing nanocarriers, being used as promising vaccines for antigen-specific immunotherapy of MS. We emphasize on liposomes, as well as lipid- and polymer-based nanoparticles. Finally, we highlight the future perspectives given by the nanotechnology field toward the improvement of the current treatment of MS and its animal model, experimental autoimmune encephalomyelitis (EAE)

Lipid Nanoparticles as Platforms for Theranostic Purposes: Recent Advances in the Field

Lipid nanoparticles (LNPs) are the first approved nanomedicines and the most well-studied class of nanocarriers for drug delivery. Currently, they are in the frontline of the pandemic fight as vaccine formulations and therapeutic products. However, even though they are so well-studied, new materials and new modifications arise every day that can improve their properties. Their dynamic nature, especially the liquid crystal state of membranes, is under constant investigation and it is that which many times leads to their complex biological behavior. In addition, newly discovered biomaterials and nanoparticles that possess promising effects and functionalities, but also toxicity and/or poor pharmacokinetics, can be combined with LNPs to ameliorate their properties. As a result, many promising theranostic applications have emerged during the past decade, proving the huge potential of LNPs in the field. In the present review, we summarize some of the most prominent classes of LNPs for nanotheranostic purposes, and present state-of-the-art research examples, with emphasis on the utilized biomaterials and the functionality that they confer to the resultant supramolecular nanosystems, in relation to diagnostic and therapeutic modalities. Although there has been unprecedented progress in theranostics, the translational gap between the bench and the clinic is undeniable. This issue must be addressed by experts in a coordinated way, in order to fully exploit these nanomedicines for the benefit of the society

Lipid Nanoparticles as Platforms for Theranostic Purposes: Recent Advances in the Field

Lipid nanoparticles (LNPs) are the first approved nanomedicines and the most well-studied class of nanocarriers for drug delivery. Currently, they are in the frontline of the pandemic fight as vaccine formulations and therapeutic products. However, even though they are so well-studied, new materials and new modifications arise every day that can improve their properties. Their dynamic nature, especially the liquid crystal state of membranes, is under constant investigation and it is that which many times leads to their complex biological behavior. In addition, newly discovered biomaterials and nanoparticles that possess promising effects and functionalities, but also toxicity and/or poor pharmacokinetics, can be combined with LNPs to ameliorate their properties. As a result, many promising theranostic applications have emerged during the past decade, proving the huge potential of LNPs in the field. In the present review, we summarize some of the most prominent classes of LNPs for nanotheranostic purposes, and present state-of-the-art research examples, with emphasis on the utilized biomaterials and the functionality that they confer to the resultant supramolecular nanosystems, in relation to diagnostic and therapeutic modalities. Although there has been unprecedented progress in theranostics, the translational gap between the bench and the clinic is undeniable. This issue must be addressed by experts in a coordinated way, in order to fully exploit these nanomedicines for the benefit of the society