Background/Objectives: Ceftriaxone (Ctx) is a third-generation cephalosporin widely used to treat infections caused by Gram-positive and Gram-negative bacteria. However, its clinical efficacy may be limited by rapid systemic elimination and suboptimal tissue distribution. Erythrocyte-based targeted drug delivery systems (TDDSs) have emerged as a promising approach to prolong drug circulation and enhance site-specific accumulation. This study investigated the pharmacokinetic profile and tissue distribution of ceftriaxone encapsulated in autologous erythrocytes (RBC-Ctx) compared with free ceftriaxone (Free-Ctx) following intravenous administration in rats. Methods: Ceftriaxone was encapsulated into autologous rat erythrocytes using a hypoosmotic hemolysis loading technique. Drug-loaded erythrocytes are called pharmacocytes. Adult male Wistar rats received a single intravenous injection of Free-Ctx or RBC-Ctx at an equivalent ceftriaxone dose of 340 mg/kg. Plasma samples were collected over 24 h for pharmacokinetic analysis, while the liver, spleen, lungs, kidneys, heart, pancreas, and skeletal muscle were harvested at 1 and 12 h for tissue distribution studies. Ceftriaxone concentrations were quantified by high-performance liquid chromatography with UV detection. Results: Erythrocyte encapsulation significantly modified the pharmacokinetic behavior of ceftriaxone. Compared with Free-Ctx, RBC-Ctx prolonged the elimination half-life (4.4 ± 0.6 vs. 1.8 ± 0.1 h), increased systemic exposure (AUC₀–last, 1.6 ± 0.1 vs. 1.2 ± 0.2 mg·h/mL), reduced total body clearance (218.2 ± 11.0 vs. 294.0 ± 48.8 mL/h/kg), and increased the apparent volume of distribution at steady state (688.3 ± 61.0 vs. 435.0 ± 23.1 mL/kg). In addition, RBC-Ctx was associated with a distinct relative tissue-distribution pattern of ceftriaxone, particularly in reticuloendothelial system-rich organs such as the liver and spleen, while ceftriaxone remained detectable in several tissues at 12 h after administration. In contrast, ceftriaxone concentrations following Free-Ctx declined markedly or became undetectable over the same period. Conclusions: Encapsulation of ceftriaxone into autologous erythrocytes substantially prolonged systemic circulation, enhanced drug exposure, reduced clearance, and altered the relative tissue distribution of ceftriaxone. These findings demonstrate that erythrocyte-based carriers effectively modulate ceftriaxone pharmacokinetics and tissue distribution, supporting their potential as a targeted antibiotic delivery platform for improving antimicrobial therapy, particularly for infections involving reticuloendothelial system-associated tissues. Further studies in experimental models of infection and inflammation are warranted to evaluate therapeutic efficacy under pathological conditions and to optimize this delivery strategy.

Introduction. The study of transport systems for targeted drug delivery is considered to be one of the promising areas of modern experimental and clinical medicine. Preclinical studies confirm the feasibility of creating a cellular system for targeted delivery of interleukin-1β in the body, based on autologous red blood cell ghosts, to improve the outcomes of treatment of purulent-inflammatory soft tissue diseases. The acute toxicity study is a crucial step in the preclinical safety study of autologous erythrocyte ghosts containing interleukin-1β. Aim. To study the acute toxicity of Interleukin-1β, encapsulated in autologous rat erythrocyte ghosts. Materials and methods. Interleukin – 1 beta was encapsulated in autologous red blood cells of rats by the method of hypoosmotic hemolysis. A study of the acute toxicity of Interleukin-1β encapsulated in autologous erythrocyte ghosts was conducted on white outbred rats of both sexes, weighing 250-300 g (40 animals in the main group and 50 in the control group). In the control group, the studied drug was administered in free form as an injection solution intravenously once into the femoral vein. In the main group, interleukin-1β encapsulated in autologous erythrocyte ghosts (pharmacocytes) was administered into the femoral vein. The range of administered doses of interleukin-1βwas from 0.07 μg/kg to 20 μg/kg. During the 14 days, the rats of the main and control groups were under observation, at a constant (26-28°C) ambient temperature, and were kept with constant access to water and food. The timing of intoxication onset and animal death was recorded, with a detailed description of the observed clinical manifestations. On day 15, all animals from both groups were euthanized under deep anesthesia, performed in compliance with the principles of humane treatment of experimental animals, followed by pathomorphological examination. Results. The LD50 for the free form of interleukin-1β was established at 15,030 ng/kg. Within the dose range used, it was not possible to determine the LD50 for interleukin-1β encapsulated in autologous red blood cell ghosts, as further dose escalation was technically challenging. Pathomorphological studies showed that administration of free interleukin-1β in the control group animals induced a pronounced inflammatory reaction in the subcutaneous adipose tissue and a moderate inflammatory response in the liver and kidneys. In contrast, administration of interleukin-1β encapsulated in autologous red blood cell ghosts caused only minor degenerative changes in the tissues and was manifested by moderate signs of venous congestion. Conclusion. The results of the study of acute toxicity of interleukin-1βdeposited in autologous red blood cell ghosts prove that pharmacocytes can significantly reduce the toxicity of the drug. We assume that the decreased toxicity of interleukin-1β upon encapsulation in autologous red blood cell ghosts is associated with altered pharmacokinetics. Введение. Одним из перспективных направлений современной медицины является использование транспортных систем для целенаправленной доставки лекарственных препаратов. Доклинические исследования подтверждают возможность создания клеточной системы для направленной доставки интерлейкин-1β в организме на основе теней аутологичных эритроцитов для улучшения результатов лечения гнойно-воспалительных заболеваний мягких тканей. Исследование острой токсичности является важным этапом доклинического исследования безопасности аутологичных теней эритроцитов, содержащих интерлейкин-1β. Цель: изучение острой токсичности Интерлейкина-1β, инкапсулированного в аутологичные тени эритроцитов крыс. Материал и методы: Интерлейкин – 1 бета был инкапсулирован в аутологические эритроциты крыс по методике гипоосмотического гемолиза. Для изучения острой токсичности инкорпорированного препарата использовали белых беспородных крыс обоего пола массой 250-300 г. В экспериментальной группе было 40 голов, в контрольной –50 голов крыс. В контрольной группе интерлейкин-1β вводили в свободной форме в бедренную вену. В основной группе вводили в бедренную вену интерлейкин-1β, инкапсулированный в аутологичные тени эритроцитов (фармакоциты). Диапазон вводимых доз интерлейкина - 1β от 0,07мкг/кг до 20 мкг/кг. В течение 14 дней крысы находились под наблюдением и содержались при постоянной температуре окружающей среды (26-28°C) со свободным доступом к пище и воде. Регистрировали сроки развития интоксикации и гибели животных с подробным описанием наблюдаемой клинической картины. На 15-й день все животные из обеих групп были подвергнуты...

Liver-targeted drug delivery offers opportunities to increase therapeutic exposure at sites of hepatic disease while limiting systemic toxicity; however, successful targeting requires more than preferential accumulation of a carrier within the liver. This narrative review critically summarizes recent advances in synthetic, biological, and biomimetic delivery platforms, including lipid, polymeric, inorganic, and protein-based nanoparticles, nucleic acid nanocarriers, extracellular vesicles, plant-derived nanovesicles, cell-mediated systems, and cell membrane-coated nanoparticles. A literature search was conducted using PubMed, Web of Science, and Embase, with emphasis on studies published during the last decade and updated through 24 August 2026. Particular attention is given to the biological determinants of hepatic biodistribution, including sinusoidal architecture, physicochemical carrier properties, protein corona formation, receptor–ligand interactions, and disease-associated alterations in the hepatic microenvironment. The review distinguishes organ-level hepatic accumulation from cell-specific uptake and productive intracellular delivery and discusses strategies directed toward hepatocytes, hepatic stellate cells, Kupffer cells and other macrophages, liver sinusoidal endothelial cells, neutrophils, and additional immune-cell populations. Major delivery platforms are critically compared with respect to the evidence supporting targeting specificity, cargo compatibility, administration route, reported safety and immunogenicity, manufacturability, analytical characterization, and translational maturity. Particular consideration is given to extracellular vesicle- and plant-derived nanovesicle-based approaches, for which biological activity, biodistribution, standardization, and scalability remain important areas of investigation. Overall, current research in liver-targeted delivery is increasingly focused on moving beyond nonspecific organ accumulation toward disease-adapted, cell-specific, and intracellularly productive delivery, although substantial biological, manufacturing, and regulatory challenges remain before many emerging approaches can achieve routine clinical translation.

Background/Objectives: Diabetic foot ulcers are characterized by persistent inflammation, impaired angiogenesis, and delayed tissue regeneration. Epidermal growth factor (EGF) is an important regulator of wound repair; however, its therapeutic application may be limited by rapid degradation and poor retention within the wound environment. This study investigated the therapeutic efficacy of local administration of EGF and ceftriaxone using autologous red blood cell-derived carriers (RBCDCs) in an experimental model of diabetic wound healing in rats. Methods: Experiments were conducted on 30 albino Wistar rats (250 ± 20 g) with experimentally induced diabetic wounds. In the RBCDC treatment groups, separately prepared drug-loaded RBCDC formulations containing EGF or ceftriaxone were locally administered into the wound. The corresponding comparison groups received the same active agents in free form according to an identical treatment schedule, while an additional control group received topical Levomekol. Results: RBCDC-mediated administration of EGF and ceftriaxone significantly accelerated wound closure and was associated with earlier resolution of inflammation, granulation tissue maturation, re-epithelialization, collagen deposition, and angiogenesis compared with the corresponding free-drug formulations. On day 9, tissue EGF concentration was higher in the RBCDC (EGF + Ctx) group than in the corresponding free-drug group. Additional formulation characterization demonstrated ceftriaxone encapsulation and in vitro release from RBCDCs, as well as in vitro EGF release from EGF-loaded RBCDCs. Conclusions: Autologous RBCDCs represent a promising local drug-carrier platform for the administration of regenerative and antimicrobial agents in experimental diabetic wounds. Further studies are required to establish local pharmacokinetics, systemic exposure, carrier stability, and the mechanisms responsible for the observed therapeutic effects.

Background/Objectives: Acute pancreatitis (AP) is a common inflammatory disorder associated with substantial morbidity, mortality, and healthcare burden, particularly in patients with systemic inflammatory response syndrome (SIRS), pancreatic necrosis, and multiple organ dysfunction syndrome (MODS). Despite advances in intensive care management, nutritional support, and minimally invasive interventions, effective pharmacological therapies targeting the underlying inflammatory and enzymatic mechanisms remain limited. Protease activation, excessive inflammation, and immune dysregulation are key drivers of AP progression. Ulinastatin, a broad-spectrum serine protease inhibitor, exerts anti-inflammatory, antioxidant, and organ-protective effects by modulating protease activity, NF-κB signaling, cytokine production, and inflammasome activation. However, conventional intravenous administration is limited by rapid systemic clearance, nonspecific distribution, and insufficient drug exposure at sites of pancreatic inflammation, necessitating repeated dosing. This narrative review aims to evaluate the scientific rationale and the therapeutic potential of ulinastatin-loaded erythrocyte-based drug delivery systems as an innovative strategy for improving the efficacy of acute pancreatitis therapy by optimizing the sustained anti-inflammatory effect of ulinastatin in foci of pancreatic inflammation. Methods: Qualitative narrative synthesis of relevant experimental and clinical literature on AP pathogenesis, ulinastatin pharmacology and therapy, protease inhibition, erythrocyte ghosts, erythrocyte pharmacocytes, and erythrocyte-based drug delivery systems was critically reviewed. The analysis focused on evidence relevant to pancreatic inflammation, drug-delivery performance, potential therapeutic benefits, and translational limitations. Results: Available evidence supports the pharmacological relevance of ulinastatin in inflammatory and protease-mediated conditions and identifies erythrocyte-derived carriers as a potential platform for drug encapsulation, prolonged circulation, and controlled drug release. Direct experimental studies investigating ulinastatin-loaded erythrocyte pharmacocytes in AP are currently lacking. Conclusions: By combining the pharmacological properties of ulinastatin with the physiological advantages of erythrocyte-mediated drug delivery, this approach may offer potential therapeutic benefits. However, these potential advantages remain hypothetical and require validation through dedicated pharmaceutical characterization, pharmacokinetic, biodistribution, and efficacy studies. Ulinastatin-loaded erythrocyte pharmacocytes represent a scientifically plausible but currently unvalidated drug delivery strategy for AP. This narrative review critically examines the therapeutic rationale for combining ulinastatin with erythrocyte-derived drug carriers as a potential targeted delivery strategy for acute pancreatitis. It synthesizes relevant evidence on ulinastatin pharmacology, erythrocyte-based drug delivery, inflammatory mechanisms, and the limitations of conventional systemic administration. Particular attention is given to the potential advantages, translational challenges, and key research gaps associated with this proposed approach. Further preclinical studies are warranted to comprehensively evaluate their pharmacokinetic properties, biological activity, safety, therapeutic efficacy, and potential for clinical translation.