Synthetic Polymer-Based Nanoparticles: Intelligent Drug Delivery Systems

One of the most promising strategies to improve the bioavailability of active pharmaceutical ingredients is based on the association of the drug with colloidal carriers, for example, polymeric nanoparticles, which are stable in biological environment, protective for encapsulated substances and able to modulate physicochemical characteristics, drug release and biological behaviour. The synthetic polymers possess unique properties due to their chemical structure. Some of them are characterized with mucoadhesiveness; another can facilitate the penetration through mucous layers; or to be stimuli responsive, providing controlled drug release at the target organ, tissues or cells; and all of them are biocompatible and versatile. These are suitable vehicles of nucleic acids, oligonucleotides, DNA, peptides and proteins. This chapter aims to look at the ‘hot spots’ in the design of synthetic polymer nanoparticles as an intelligent drug delivery system in terms of biopharmaceutical challenges and in relation to the route of their administration: the non-invasive—oral, transdermal, transmucosal (nasal, buccal/sublingual, vaginal, rectal and ocular) and inhalation routes—and the invasive parenteral route

Aerosol vaccines – perspectives and therapeutic impact

Introduction: Aerosol vaccination is a promising non-injectable method that provides immune resistance to pathogens since it follows the natural route of transmission of many infectious agents. The immune response, occurring after intranasal or respiratory vaccine administration, provides credible protection due to the common mucosal immune system, excellent blood supply, and lung permeability.Aim: The study aims to highlight the unconventional and perspective application use of aerosol dosage forms as a technological approach for vaccine drug delivery.Materials and Methods: A detailed literature survey in scientific databases such as PubMed, ScienceDirect, ResearchGate has been conducted, and the relevant information has been summarized and interpreted.Results: The aerosol vaccination method, as an alternative to the subcutaneous, intramuscular or intradermal application route, ensures defense against the inhaled pathogens, avoiding at the same time drawbacks associated with the injection administration such as the risk of reuse of disposable medical consumables, potential spreading of blood-borne diseases and the necessity of qualified medical personnel. Additionally, aerosol vaccination is an easier and more practical approach for patients, leading to improved compliance. Vaccines applied by the inhalation or nasal route of administration could be a successful approach for the treatment of diseases such as measles, tuberculosis, or influenza A, that although preventable, remain a global challenge.Conclusion: The aerosol method is promising for vaccine delivery with the potential to be fully evaluated in the upcoming years.                                                                                   

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

Silver Nanoparticles as Multi-Functional Drug Delivery Systems

Nanoparticles can surmount some essential problems of conventional small molecules or biomacromolecules (e.g., DNA, RNA, and protein) used in some diseases by allowing targeted delivery and overcome through biological barriers. Recently, silver nanoparticles have been harnessed as delivery vehicles for therapeutic agents, including antisense oligonucleotides, and other small molecules. Silver is the most profit-oriented precious metal used in the preparation of nanoparticles and nanomaterials because of its antibacterial, antiviral, antifungal, antioxidant and unusually enhanced physicochemical properties compared to the bulk material such as optical, thermal, electrical, and catalytic properties. Small silver nanoparticles offer many advantages as drug carriers, including adjustable size and shape, enhanced stability of surface-bound nucleic acids, high-density surface ligand attachment, transmembrane delivery without harsh transfection agents, protection of the attached therapeutics from degradation, and potential for improved timed/controlled intracellular drug-delivery. Plant-mediated synthesis of silver nanoparticles is gaining interest due to its inexpensiveness, providing a healthier work environment, and protecting human health leading to lessening waste and safer products. The chapter presents the essential physicochemical characteristics, antibacterial, and anticancer properties which silver nanoparticles obtained by plant-mediated methods possess, and their application as drug-delivery systems with a critical view on the possible toxicity on the human body

Stability study of extemporaneously compounded nitrofurantoin oral suspensions for pediatric patients

Aim: To evaluate the stability of nitrofurantoin suspended in different extemporaneously compounded vehicles after storage at 4°C and at 25°C. To formulate an effective, readily available vehicle that can guarantee extended stability and precise dosing. Materials and methods: Nitrofurantoin was suspended at a concentration of 10 mg/mL in seven different vehicles compounded of different blends of Syrupus simplex, sorbitol 70%, methylcellulose 1%, gummi arabici 1%, gummi xanthani 1%, and sodium carboxymethylcellulose (NaCMC) 1%. Samples of 100 mL of every compounded suspension were stored in dark in graded glass bottles at 4°C and at 25°C. Samples were analyzed at the beginning and every 10 days up to day 30 and every 30 days after. Variations of physical properties such as sedimentation, ease of resuspension, color and odor were evaluated visually and organoleptically. Rheological analysis was also performed in order to determine suspensions’ behavior during storage and dosing. Variations in nitrofurantoin concentration and pH were evaluated with suitable analytical procedure (UV-Vis; HPLC; pH/ORP). Microbiological stability was evaluated via incubation on suitable culture media. Results: To the 30th day, only three of the compounded suspensions exhibited significant physical stability and slight change in taste and odor stored at both temperatures. Two samples stored at 25°C exhibited nitrofurantoin concentration greater than 95% and 4 samples stored at 4°C – concentration greater than 95%. All models showed no microbial growth up to day 30. At 120 days, only three of the compounded suspensions, stored at 4°C, exhibited relatively high nitrofurantoin concentrations: 88.2%, 92%, and 81.1%, respectively. Only one model suspension showed chemical and physical stability (≥95% of the initial concentration) for 102 days. No model suspension remained sterile after 30 days. Conclusions: The suspensions compounded with vehicles of blends of syrups, xanthan, croscarmellose (NaCMC), and sorbitol exhibited low to none sedimentation, good uniformity of content and are suitable organoleptically for pediatric administration. The model suspension stored at 4°C (NTF VII 4°C – with major excipients: sucrose 16%, sorbitol 17%, xanthan gum 0.25%, NaCMC 0.25%) stands out with nitrofurantoin concentration higher than 95% along with no or little signs of sedimentation. After adding a suitable preservative agent or system, a formulation with these characteristics might have an expiration date of at least 90 days

BIOLOGICAL ACTIVITY OF BULGARIAN FOLIA BETULAE DRY EXTRACT

Objective: The aim of this study was to investigate the biological activity of dry Folia Betulae (FB) extract.Methods: Extracts from birch leaves were obtained by different technological methods–maceration and percolation, extraction with different concentrations of ethanol, changes in temperature regimen. The influence of the technological factors on the content of the biologically active substances (BAS) was examined. A phytochemical characterization of the extracts and their standardization were made, according to important groups of BAS–flavonoids (rutin, quercetin) and terpenes (betulin and betulinic acid), by means of HPLC methods for detection and quantitative determination. A model extract, with optimal content of BAS was chosen for subsequent in vitro investigation of its biological activity. Antimicrobial activity was studied via in vitro tests using bacterial isolates–Staphylococcus aureus, Escherichia coli and Candida albicans. The physiological activity was investigated by using in vitro test with smooth muscle strips. The antiproliferative activity of FB extract on eukaryotic cells was examined on cell cultures in vitro. Two cell cultures were used: the mouse lymphoma cell line L5178Y and the serum-free McCoy-Plovdiv cells.Results: The dry extract from FB has a dose–dependent antibacterial effect. The bactericidal effect on Staphylococcus aureus is stronger than the one on Escherichia coli. Results prove that adding the extract leads to stimulating effect on muscle contractility. It demonstrates biological activity, expressed as changes in cell morphology, proliferation and vitality as well as initiation of apoptosis.Conclusion: The results obtained largely overlap with literature data and explain some of the applications of this plant in traditional medicine.Â

Carbopol hydrogel/sorbitan monostearate-almond oil based organogel biphasic formulations: Preparation and characterization of the bigels

Purpose: To obtain and evaluate carbopol hydrogel/sorbitan monostearate-almond oil-based organogel biphasic formulations (bigels) as a semi-solid vehicle for medicated topical applications.Methods: Bigel formulations were obtained under mild conditions at a hydrogel/organogel ratio of 80/20, 70/30, and 60/40 (w/w). Their stability, viscosity, spreadability, microarchitecture, and acute skin toxicity were evaluated.Results: Two formulations, prepared at ratios of 80/20 and 70/30, were stable based on intermediate stability testing, and had a similar viscosity and spreadability (38.0 ± 1.0 mm and 37.3 ± 0.6 mm, p > 0.05, respectively). Both of these formulations had a bimodal droplet size distribution and very similar values for the droplet mean diameter (0.33 ± 0.05 μm and 2.35 ± 0.44; and 0.34 ± 0.04 μm and 2.59 ± 0.21 μm). The formulation obtained at a ratio of 60/40 was unstable during storage. The in vivo results did not reveal any signs of skin toxicity.Conclusion: Considering their beneficial properties, the developed bigels are a potential semi-solid vehicle for topical application and exhibit a moisturizing effect.Keywords: Almond oil, Bigels, Carbopol hydrogel, Moisturizing effect, Organogel, Sorbitan monostearat

Application Of Digital Technologies In The Pharmaceutical Sector

The introduction of digital technologies into the pharmaceutical sector is associated with the digital transformation and the shift in business models and production processes of the organizations that operate in the field. Digitalization provides an opportunity to develop and implement innovative technologies and medicines and their safety and efficacy monitoring. Various intelligent medical devices are used to collect and process data and allow different stakeholders (such as patients and health professionals) to exchange information, thus facilitating the process of therapy decision-making and therapy follow-up. Digital services improve patients' access to health information; they allow for improved therapeutic results and quality of life. In the pharmaceutical sector in Europe and America, digital technologies find application in the following areas: drug therapy management, pharmacogenomics, 3D printing of medicines, personalized digital pharmaceutical care, automatic dosing devices, drug reminder devices, and prevention of counterfeit medicines entering the legal supply chain. In Bulgaria, digital solutions are used to prevent the entry of counterfeit medicines via the introduction of a verification system; to create platforms and applications for health information and communication among patients, health professionals, and institutions, including through the introduction of e-prescriptions and e-referrals.This paper aims to demonstrate the benefits of digitalization for the pharmaceutical practice in providing personalized pharmaceutical and health care, which leads to an increase in patient satisfaction and a reduction in healthcare costs

Adamantane-containing drug delivery systems

Adamantane is a weakly functional hydrocarbon widely used to develop new drug molecules to improve their pharmacokinetic and pharmacodynamic parameters. The compound has an affinity for the lipid bilayer of liposomes, enabling its application in targeted drug delivery and surface recognition of target structures. This review presents the available data on developed liposomes, cyclodextrin complexes, and adamantane-based dendrimers. Adamantane has been used in two ways – as a building block to which various functional groups are covalently attached (adamantane-based dendrimers) or as a part of self-aggregating supramolecular systems, where it is incorporated based on its lipophilicity (liposomes) and strong interaction with the host molecule (cyclodextrins). Adamantane represents a suitable structural basis for the development of drug delivery systems. The study of adamantane derivatives is a current topic in designing safe and selective drug delivery systems and molecular carriers