Solid lipid nanoparticles and nanostructured lipid carriers: current perspectives in wound care

Introduction: When the skin’s integrity is compromised, one or more of its safeguarding mechanisms can be impaired. In this line of thought, wound healing often requires topical delivery of active pharmaceutical ingredients (APIs) to ensure proper skin regeneration. Unfortunately, the dermal route of administration has drawbacks in terms of insufficient drug penetration and low bioavailability. The employment of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) in this field could be a promising approach due to their ability to increase drug permeation and provide sustained release and targeted delivery.Aim: This review aims to provide an update on the use of SLNs and NLCs in wound management and contribute to the advancement of innovative and effective treatments.Materials and Methods: Systematic research was conducted in various databases to identify relevant scientific publications on the use of lipid nanoparticles (LNPs) as drug delivery systems for topical wound care.Results and Conclusion: Lipid nanoparticles, including SLNs and NLCs, have been extensively investigated as delivery platforms for a wide range of compounds in wound healing. The encapsulation of synthetic, semi-synthetic, and natural molecules within these lipid-based nanosystems has demonstrated promising outcomes such as enhanced anti-inflammatory and antimicrobial effects, as well as improved wound healing, leading to faster regeneration and increased tear resistance. Overall, lipid nanoparticles offer a valuable strategy for wound management with the potential to revolutionize the field and offer improved therapeutic options for better patient outcomes. 1. Romanovsky AA. Skin temperature: its role in thermoregulation. Acta Physiol. 2014;210(3):498-507. doi: 10.1111/apha.12231. 2. Nguyen AV, Soulika AM. The dynamics of the skin's immune system. Int J Mol Sci. 2019;20(8):1811. doi: 10.3390/ijms20081811. 3. Eyerich S, Eyerich K, Traidl-Hoffmann C, Biedermann T. Cutaneous barriers and skin immunity: differentiating a connected network. Trends Immunol. 2018;39(4):315-27. doi: 10.1016/j.it.2018.02.004. 4. Quaresma JAS. 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Possibilities For Conducting Treatment With Unauthorized Medicinal Products In Bulgaria

The regulation of drug use has been developing rapidly over the last 50 years, with an emphasis on the safety, quality and efficacy of medicinal products through the introduction of authorization procedures for a medicinal product;It has been established that there are a number of circumstances that require exceptions to the existing requirements for the use of only authorized drugs - pediatric and geriatric patients, highly resistant diseases, patients in the terminal phase and others.Similar situations are provided for in the Law on Medicinal Products in Human Medicine (LMPHM) - groups of drugs are defined that could be used without an authorization for use under strictly defined specific conditions;One of the most frequently used options is that for the treatment of a specific patient with a medicinal product not authorized in Bulgaria, as this is done according to Art. 266a of the LMPHM

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

Dermal Drug Delivery of Phytochemicals with Phenolic Structure via Lipid-Based Nanotechnologies

Phenolic compounds are a large, heterogeneous group of secondary metabolites found in various plants and herbal substances. From the perspective of dermatology, the most important benefits for human health are their pharmacological effects on oxidation processes, inflammation, vascular pathology, immune response, precancerous and oncological lesions or formations, and microbial growth. Because the nature of phenolic compounds is designed to fit the phytochemical needs of plants and not the biopharmaceutical requirements for a specific route of delivery (dermal or other), their utilization in cutaneous formulations sets challenges to drug development. These are encountered often due to insufficient water solubility, high molecular weight and low permeation and/or high reactivity (inherent for the set of representatives) and subsequent chemical/photochemical instability and ionizability. The inclusion of phenolic phytochemicals in lipid-based nanocarriers (such as nanoemulsions, liposomes and solid lipid nanoparticles) is so far recognized as a strategic physico-chemical approach to improve their in situ stability and introduction to the skin barriers, with a view to enhance bioavailability and therapeutic potency. This current review is focused on recent advances and achievements in this area

In silico study of the toxicity of hyperforin and its metabolites

St. John’s wort is a medicinal herb well-known for its antidepressant, anti-inflammatory, antimycotic, and wound-healing properties. Hyperforin, the major phloroglucinol derivative, has been implicated as one of the main contributors to these therapeutic effects. Because of its high reactivity, this phytochemical can cause various adverse effects, such as allergic reactions, dizziness, dry mouth, and fatigue. To predict critical parameters of hyperforin’s possible behavior after oral administration, in silico methods were applied. The pharmacokinetic profile, bioactivity, and toxicity of the phytochemical were analyzed by applying Molinspiration cheminformatics, SwissADME, PreADME/Tox, and OECD QSAR Toolbox software. The results showed adequate absorption, a high affinity for plasma proteins, and a prolonged renal excretion of the acylphloroglucinol. The high metabolic activity, a reason for potential cyto- and genotoxicity, and the predicted carcinogenicity and mutagenicity of hyperforin, necessitate further in vitro and in vivo tests

Advances in the Prophylaxis of Respiratory Infections by the Nasal and the Oromucosal Route: Relevance to the Fight with the SARS-CoV-2 Pandemic

In this time of COVID-19 pandemic, the strategies for prevention of the infection are a primary concern. Looking more globally on the subject and acknowledging the high degree of misuse of protective face masks from the population, we focused this review on alternative pharmaceutical developments eligible for self-defense against respiratory infections. In particular, the attention herein is directed to the nasal and oromucosal formulations intended to boost the local immunity, neutralize or mechanically “trap” the pathogens at the site of entry (nose or mouth). The current work presents a critical review of the contemporary methods of immune- and chemoprophylaxis and their suitability and applicability in topical mucosal dosage forms for SARS-CoV-2 prophylaxis

Bigel formulations of St. John’s wort extract in wound healing: toxicological aspects

AbstractThis study aimed to investigate the toxicological profile of hyperforin (HP) in silico and to assess it in vivo after topical application of an HP-rich St. John’s wort (SJW) extract. The former analysis predicted low toxicity because of HP’s inability to bind DNA or proteins, but structural alerts for skin irritation/corrosion, carcinogenicity, and mutagenicity were found. Animal studies involved the treatment of excision wounds in Wistar rats with poloxamer 407/borage oil formulations (bigels; Bs) containing HP-rich SJW extract previously developed by us. The effects of semisolids comprising ‘free’ extract (B/SJW) or extract loaded in nanostructured lipid carriers (B/NLC-SJW) were compared to positive (commercial herbal product) and negative (untreated) controls after 2-, 7-, 14-, and 21-day applications. Malondialdehyde (MDA) and ABTS assays evaluated the degree of oxidative stress—treatment with bigels did not affect MDA favorably but led to an increased radical-cation scavenging capacity (compared to controls). Gamma-glutamyl transferase (GGT), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and lactate dehydrogenase (LDH) enzyme levels were measured as indicators for liver/tissue damage. Treatment with both B/SJW and B/NLC-SJW for 21 days resulted in lower GGT and ASAT levels than those in controls. Two-day application of the biphasic semisolids contributed to normalized ALAT levels (lower than in both negative and positive controls), and the same trends were observed in LDH levels after a 7-day treatment. The promising results obtained after the B/NLC-SJW application suggest that this drug delivery system may not only preserve HP in SJW extract effectively but also ‘expose’ its cyto-/hepatoprotective potential

Bigel formulations of St. John’s wort extract in wound healing: toxicological aspects

This study aimed to investigate the toxicological profile of hyperforin (HP) in silico and to assess it in vivo after topical application of an HP-rich St. John’s wort (SJW) extract. The former analysis predicted low toxicity because of HP’s inability to bind DNA or proteins, but structural alerts for skin irritation/corrosion, carcinogenicity, and mutagenicity were found. Animal studies involved the treatment of excision wounds in Wistar rats with poloxamer 407/borage oil formulations (bigels; Bs) containing HP-rich SJW extract previously developed by us. The effects of semisolids comprising ‘free’ extract (B/SJW) or extract loaded in nanostructured lipid carriers (B/NLC-SJW) were compared to positive (commercial herbal product) and negative (untreated) controls after 2-, 7-, 14-, and 21-day applications. Malondialdehyde (MDA) and ABTS assays evaluated the degree of oxidative stress—treatment with bigels did not affect MDA favorably but led to an increased radical-cation scavenging capacity (compared to controls). Gamma-glutamyl transferase (GGT), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and lactate dehydrogenase (LDH) enzyme levels were measured as indicators for liver/tissue damage. Treatment with both B/SJW and B/NLC-SJW for 21 days resulted in lower GGT and ASAT levels than those in controls. Two-day application of the biphasic semisolids contributed to normalized ALAT levels (lower than in both negative and positive controls), and the same trends were observed in LDH levels after a 7-day treatment. The promising results obtained after the B/NLC-SJW application suggest that this drug delivery system may not only preserve HP in SJW extract effectively but also ‘expose’ its cyto-/hepatoprotective potential.</p