Aspects of Nanoparticle-Targeted Therapy

Conventional dosage forms often have disadvantages: high dose, low efficiency, toxicity, and unwanted side effects. Drug delivery systems (DDSs) are characterized by modified release and can overcome these drawbacks.In many diseases, controlling the delivery and release of drugs to target tissues and organs is a challenge. The utilization of nano-sized drug-delivery systems provides a much larger surface area, affects the rate of dissolution, increases bioavailability at the site of action, and leads to a decrease in the administered dose of the medicinal product and a reduction of adverse drug reactions.The term "nanoparticles" (NPs) refers to materials with a size between 1 and 1000 nm. Nanoparticles' ability to penetrate cells faster than other macromolecules makes them suitable carriers for drug delivery systems.Peptides are attracting great interest in biomedicine as a new material that can exhibit functionalities characteristic of proteins and a high degree of modularity in molecular design.According to many researchers, combining peptides with non-biological materials (e.g., low molecular weight compounds, metal chelates, polymers, and hydrogels) is a promising approach to overcome their drawbacks (their low metabolic stability to proteolysis in the gastrointestinal tract, low levels of absorption after oral administration, decreased penetration, and rapid excretion via the liver and kidneys). The potential of NPs to conjugate with them leads to improved functions and the manifestation of synergism. As a result, conjugates of peptides with nanoparticles represent a promising platform for use in biomedicine

Self-Emulsifying Drug Delivery Systems as an Approach to Improved Oral Bioavailability of Drugs

The oral route of drug administration is the most effective and the most widely applicable, as it is characterized by high therapeutic efficiency, a low production cost, and very good patient acceptance. Before a drug enters the bloodstream, it must go through stages of dissolution and overcome biological membranes. However, most drugs are characterized by low solubility and/or permeability in the gastrointestinal tract environment. These disadvantages can be overcome by various technological approaches, such as micronization, the formation of salts and complexes, solid dispersions, the use of mucoadhesive polymers, as well as lipid-based drug delivery systems such as the self-emulsifying systems (SEDDS). In recent years, SEDDS have been one of the most popular approaches to increasing oral bioavailability, as they have the potential to reduce the administered dose and protect unstable drugs from the aggressive conditions in the gastrointestinal tract.Depending on their preparation and composition, SEDDS can improve the deficiencies of drugs belonging to biopharmaceutical classes II to IV. Furthermore, depending on the type of dispersion formed, they can be classified into micro-SEDDS, nano-SEDDS, o/w-SEDDS, and w/o/w-SEDDS.

Parkinson's Disease: Technological Approaches for Optimized Therapeutic Efficacy of Levodopa

Parkinson's disease is a progressive neurodegenerative disease affecting more than 10 million patients worldwide. The leading cause of this pathological condition is an imbalance between dopaminergic and cholinergic systems due to dopaminergic neurons' degeneration in the nigrostriatal pathways. The primary goal of Parkinson's therapy is to correct the levels of the mentioned neurotransmitters, and the administration of Levodopa has been accepted as a "gold standard" treatment. The amino acid precursor can successfully control the symptoms by compensating for the reduced concentration of endogenous dopamine and activating postsynaptic D-receptors in the striatum.The intensive enzymatic degradation of levodopa in the gastrointestinal tract is the main reason for its low concentration in the midbrain (~1%) and the increased frequency of adverse drug reactions. Despite numerous attempts to improve clinical efficacy, increasing bioavailability and reducing side effects remain difficult. This makes it necessary to use innovative drug delivery systems capable of overcoming the problems mentioned above.This literature review presents new technological approaches for improved delivery of levodopa to the central nervous system. Nanoparticles, liposomes, cyclodextrin complexes, carbon nanotubes, and others represent promising platforms for the delivery and controlled release of the dopamine precursor. With the ability to ensure optimal bioavailability, constant plasma concentration, minimal peripheral degradation, and reduced adverse drug reactions, they successfully overcome the shortcomings of conventional levodopa-containing dosage forms

Ex Vivo Permeation Study of Levodopa Using In Situ Gelling Systems for Nasal Drug Delivery

The intranasal drug administration route offers reduced peripheral toxicity, targeted drug delivery, and improved bioavailability, especially for therapeutics intended for the treatment of neurological disorders. The most common therapy for Parkinson's disease includes the use of the aromatic amino acid levodopa, whose chronic oral application precedes the onset of on/off phenomena, dyskinesia, and other adverse drug reactions. Additionally, levodopa has low oral bioavailability, and therapeutic challenges remain unresolved even after combining it with enzyme inhibitors. The aim of the present study is to investigate the ex vivo effects of in situ gelling systems with levodopa and the sesquiterpene alpha-bisabolol, included due to its known permeation-enhancing properties. The studied nasal formulations were designed to deliver the active pharmaceutical ingredient directly to the brain through the olfactory region of the nasal cavity, bypassing first-pass metabolism and the blood-brain barrier. Two in situ thermogelling systems were prepared, each loaded with 0.1% levodopa in Poloxamer 407 15% hydrosol, with alpha-bisabolol solubilized at 1% in the second system. The test formulations underwent an ex vivo permeation study using nasal mucosa as a membrane on a Franz diffusion cell. The results of the conducted analysis showed that the in situ gelling system containing alpha-bisabolol ensured a higher drug permeation rate (Jss) of levodopa through the mucosa (2.00 µg·cm⁻²·min⁻¹) compared to the reference formulation without alpha-bisabolol (1.35 µg·cm⁻²·min⁻¹). The well-known permeation-enhancing mechanism of alpha-bisabolol, which increases the fluidity of membrane lipids, along with the obtained results, suggests that the primary transport mechanism for levodopa is intracellular, passing through the lipid membranes of epithelial cells

Essential Oils: An Alternative to Antibiotics for Nasal Bacterial Infections

Introduction: Staphylococcus aureus (S. aureus) is the primary pathogenic bacterium found in the nasal mucosa. This Gram-positive bacterium colonizes the upper respiratory tract and skin, leading to serious infections characterized by high morbidity. The topical antibiotic mupirocin is commonly used for treating staphylococcal infections. However, excessive and irrational use of antibiotics increases the risk of microbial resistance, while the lack of new antibacterial agents raises concerns about future pandemics.Aim: This review aims to present literature data on the role of essential oils (EOs) in managing bacterial nasal infections as an alternative to conventional therapeutic approaches.Materials and Methods: A literature review was conducted using the documentary method, drawing from scientific publications in databases such as PubMed, Web of Science, ScienceDirect, and Scopus. The keywords used included nasal application, topical antibiotic, antibiotic resistance, essential oils, antibacterial effect, and Staphylococcus aureus.Results: Essential oils are known for their diverse biological effects. They may contain hundreds of chemical constituents, with monoterpenes, sesquiterpenes, and phenylpropanoids being predominant. Due to their broad spectrum of activities—including antibacterial, antiviral, anti-inflammatory, mucolytic, and bronchodilatory effects—these biologically active, volatile substances are valuable resources for anti-infective therapy in respiratory infections. Additionally, their natural origin and rich composition make them widely applicable and accessible in traditional medicine. Peppermint, pine, and eucalyptus oils are among the most commonly used in products for nasal application.Conclusion: Based on the literature review, EOs have potential in the treatment of nasal infections caused by S. aureus. These findings will be utilized in a future experiment focused on the formulation and characterization of a nasal antibacterial dosage form

Nanocarriers-Assisted Nose-to-Brain Delivery of Levodopa: Current Progress and Prospects

A challenge to contemporary medicine is still the discovery of an effective and safe therapy for symptomatic control, if not cure, of Parkinson’s disease. While the potential century’s break-through is sought and foreseen by many scientists in gene therapy, immunotherapy, new drug combinations, and neurosurgical approaches, the not-yet-conventional intranasal administration of “classic” levodopa (L-DOPA) also stands out as a perspective from which Parkinson’s patients may benefit in the short term. With the main drawbacks of the standard oral L-DOPA treatment being the extremely low systemic and cerebral bioavailability, it is widely recognized that the nasal route may turn out to be the better administration site, for it offers the alternative of direct brain delivery via the olfactory bulb (the so-called nose-to-brain axis). However, such advancement would be unthinkable without the current progress in nano-scaled drug carriers which are needed to ensure drug stability, mucosal retention and permeation, olfactory uptake, and harmlessness to the sensory neurons and respiratory cilia. This study aims to review the most significant results and achievements in the field of nano-particulate nose-to-brain delivery of L-DOPA