Search Results (8)

Radiation-induced intestinal injury (RIII), a severe complication of abdominopelvic radiotherapy, causes intestinal ischemia, ulcers, and necrosis, severely impacting patients’ quality of life. Currently, effective treatments are limited, and a specific cure remains elusive. Our previous research showed that lactoferrin (LF) can promote intestinal stem cell (ISC) proliferation and tissue repair; however, its oral administration is limited by rapid degradation in the gastric environment. In this study, we developed LF-loaded liposomal nanoparticles (Lip-LF) using a simple ethanol injection method. The optimal formulation (cholesterol/egg yolk lecithin ratio 2:8, LF concentration 12.5 mg/mL) achieved a drug-loading capacity of 6.8% and a narrow size distribution (0.2 < PDI < 0.4). In vitro experiments demonstrated that Lip-LF protected LF from pepsin degradation in simulated gastric fluid (SGF), retaining over 80% integrity after 120 min, while releasing in simulated intestinal fluid (SIF). In vivo imaging revealed prolonged gastrointestinal retention of Lip-LF compared to free LF. In a murine model of RIII (12 Gy whole-body irradiation), Lip-LF significantly restored villus counts, increased crypt height, and promoted goblet-cell regeneration. Immunohistochemical and qPCR analyses revealed enhanced ISCs proliferation and upregulation of repair-associated genes, including Pcna and Olfm4. These findings demonstrate that Lip-LF protects LF from gastric degradation and enhances its targeted delivery to the intestine, improving its therapeutic efficacy in repairing RIII. Lip-LF thus offers a promising strategy for managing RIII. Full article

Background/Objectives: The blood–brain barrier (BBB) poses a major obstacle to delivering therapeutic agents to the central nervous system (CNS), driving the need for innovative drug delivery strategies. Among these, nanoparticles (NPs) have gained attention due to their ability to enhance drug transport, improve bioavailability, and enable targeted delivery. Methods: This paper explores various surface modification strategies employed to optimize NP-mediated drug delivery across the BBB. Specifically, the functionalization of NPs with ligands such as transferrin (Tf), lactoferrin (Lf), protamine, and insulin is discussed, each demonstrating unique mechanisms for enhancing brain-targeting efficiency. In addition, this work provides a comprehensive overview of recent scientific advancements and market strategies aimed at accelerating the adoption of low-cost, surface-modified nanoparticles, ultimately improving patient access to effective CNS treatments. Conclusions: Preclinical and in vitro studies have demonstrated the effectiveness of these modifications in increasing drug retention and bioavailability in brain tissues. Additionally, while ligand-conjugated NPs hold significant promise for neuropharmacology, their clinical translation is often hindered by regulatory and economic constraints. Lengthy approval processes can slow market entry, but cost–benefit analyses indicate that surface-modified NPs remain financially viable, particularly as scalable manufacturing techniques and some ligands are cost-efficient. Full article

Lactoferrin (Lf) is a multifunctional glycoprotein with well-established antimicrobial, anti-inflammatory, and iron-binding properties. Emerging evidence suggests that Lf also plays a neuroprotective role, particularly in neurodegenerative disorders characterized by protein aggregation, such as Parkinson’s disease (PD). Alpha-synuclein (aSyn) aggregation is a pathological hallmark of PD and other synucleinopathies, contributing to neuronal dysfunction and disease progression. Recent studies indicate that Lf may interfere with aSyn aggregation, iron chelation, and modulation of oxidative stress and neuroinflammation. Additionally, Lf’s ability to cross the blood-brain barrier and its potential impact on the gut-brain axis highlight its promise as a therapeutic agent. This review explores Lf’s mechanisms of action in synucleinopathies, its potential as a disease-modifying therapy, and innovative delivery strategies that could enhance its clinical applicability. By addressing the pathological and therapeutic dimensions of aSyn aggregation, we propose Lf as a compelling candidate for future research and clinical development in neurodegenerative diseases. Full article

Liposomes serve as an effective delivery system capable of encapsulating a variety of bioactive substances. However, their structural integrity is susceptible to damage from various environmental factors, which can result in the leakage of the encapsulated bioactive agents. Consequently, identifying effective strategies to enhance the stability of liposomes has become a central focus of contemporary liposome research. Surface modification, achieved by introducing a protective layer on the liposome surface, effectively reduces liposome aggregation and enhances their stability. To this end, we designed a surface modification and constructed liposomes loaded with β-carotene through co-modification with chitosan and lactoferrin, resulting in enhanced stability. This improvement was evident in terms of storage stability, light stability, and in vitro digestion stability. The study investigated the morphology, structure, and physicochemical properties of liposomes with varying degrees of modification. CS-LF co-modified liposomes exhibited significant structural changes, with particle size increasing from 257.9 ± 6.2 nm to 580.5 ± 21.5 nm, and zeta potential shifting from negative to +48.9 ± 1.3 mV. Chitosan and lactoferrin were modified on the liposome surface through electrostatic interactions and hydrogen bonding, forming a dense protective barrier on the lipid membrane. Physicochemical analysis indicated that chitosan–lactoferrin co-modification led to a more ordered arrangement of the phospholipid bilayer, reduced membrane fluidity, and increased membrane rigidity. The interactions between chitosan, lactoferrin, and phospholipids were enhanced through hydrogen bonding, resulting in a denser surface membrane structure. This structural integrity reduced membrane permeability and improved the stability of liposomes under storage conditions, UV irradiation, and in vitro digestion. Additionally, co-modified chitosan–lactoferrin liposomes effectively alleviated lipopolysaccharide-induced inflammatory damage in mouse microglial cells by increasing cellular uptake capacity, thereby enhancing the bioavailability of β-carotene. The results of this study demonstrate that chitosan–lactoferrin co-modification significantly enhances the stability of liposomes and the bioavailability of β-carotene. These findings may contribute to the development of multi-substance co-modified liposome systems, providing a more stable transport mechanism for various compounds. Full article

Nanoparticles (NPs) have emerged as a potent choice for various applications, from drug delivery to agricultural studies, serving as an alternative and promising methodology for future advancements. They have been widely explored in delivery systems, demonstrating immense promise and high efficiency for the delivery of numerous biomolecules such as proteins and anticancer agents, either solely or modified with other compounds to enhance their capabilities. In addition, the utilization of NPs extends to antimicrobial studies, where they are used to develop novel antibacterial, antifungal, and antiviral formulations with advanced characteristics. Lactoferrin (Lf) is a glycoprotein recognized for its significant multifunctional properties, such as antimicrobial, antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. Its activity has a broad distribution in the human body, with Lf receptors present in multiple regions. Current research shows that Lf is utilized in NP technology as a surface material, encapsulated biomolecule, and even as an NP itself. Due to the abundance of Lf receptors in various regions, Lf can be employed as a surface material in NPs for targeted delivery strategies, particularly in crossing the BBB and targeting specific cancers. Furthermore, Lf can be synthesized in an NP structure, positioning it as a strong candidate in future NP-related applications. In this article, we explore the highlighted and underexplored areas of Lf applications in NPs research. Full article

Lactoferrin (Lf), a multifunctional protein found abundantly in secretions, including tears, plays a crucial role in ocular health through its antimicrobial, immunoregulatory, anti-inflammatory, and antioxidant activities. Advanced delivery systems are desirable to fully leverage its therapeutic potential in treating ocular diseases. The process of Lf quantification for diagnostic purposes underscores the importance of developing reliable, cost-effective detection methods, ranging from conventional techniques to advanced nano-based sensors. Despite the ease and non-invasiveness of topical administration for ocular surface diseases, challenges such as rapid drug elimination necessitate innovations, such as Lf-loaded contact lenses and biodegradable polymeric nanocapsules, to enhance drug stability and bioavailability. Furthermore, overcoming ocular barriers for the treatment of posterior segment disease calls for nano-formulations. The scope of this review is to underline the advancements in nanotechnology-based Lf delivery methods, emphasizing the pivotal role of multidisciplinary approaches and cross-field strategies in improving ocular drug delivery and achieving better therapeutic outcomes for a wide spectrum of eye conditions. Full article

Lactoferrin (Lf)—a glycoprotein of the transferrin family—has been investigated as a promising molecule with diverse applications, including infection inhibition, anti-inflammation, antioxidant properties and immune modulation. Along with that, Lf was found to inhibit the growth of cancerous tumors. Owing to unique properties such as iron-binding and positive charge, Lf could interrupt the cancer cell membrane or influence the apoptosis pathway. In addition, being a common mammalian excretion, Lf offers is promising in terms of targeting delivery or the diagnosis of cancer. Recently, nanotechnology significantly enhanced the therapeutic index of natural glycoproteins such as Lf. Therefore, in the context of this review, the understanding of Lf is summarized and followed by different strategies of nano-preparation, including inorganic nanoparticles, lipid-based nanoparticles and polymer-based nanoparticles in cancer management. At the end of the study, the potential future applications are discussed to pave the way for translating Lf into actual usage. Full article

Pneumococcal disease remains a global burden, with current conjugated vaccines offering protection against the common serotype strains. However, there are over 100 serotype strains, and serotype replacement is now being observed, which reduces the effectiveness of the current vaccines. Pneumococcal surface protein A (PspA) has been investigated as a candidate for new serotype-independent pneumococcal vaccines, but requires adjuvants and/or delivery systems to improve protection. Polymeric nanoparticles (NPs) are biocompatible and, besides the antigen, can incorporate mucoadhesive and adjuvant substances such as chitosans, which improve antigen presentation at mucosal surfaces. This work aimed to define the optimal NP formulation to deliver PspA into the lungs and protect mice against lethal challenge. We prepared poly(glycerol-adipate-co-ω-pentadecalactone) (PGA-co-PDL) and poly(lactic-co-glycolic acid) (PLGA) NPs using an emulsion/solvent evaporation method, incorporating chitosan hydrochloride (HCl-CS) or carboxymethyl chitosan (CM-CS) as hybrid NPs with encapsulated or adsorbed PspA. We investigated the physicochemical properties of NPs, together with the PspA integrity and biological activity. Furthermore, their ability to activate dendritic cells in vitro was evaluated, followed by mucosal immunization targeting mouse lungs. PGA-co-PDL/HCl-CS (291 nm) or CM-CS (281 nm) NPs produced smaller sizes compared to PLGA/HCl-CS (310 nm) or CM-CS (299 nm) NPs. Moreover, NPs formulated with HCl-CS possessed a positive charge (PGA-co-PDL +17 mV, PLGA + 13 mV) compared to those formulated with CM-CS (PGA-co-PDL −20 mV, PLGA −40 mV). PspA released from NPs formulated with HCl-CS preserved the integrity and biological activity, but CM-CS affected PspA binding to lactoferrin and antibody recognition. PspA adsorbed in PGA-co-PDL/HCl-CS NPs stimulated CD80+ and CD86+ cells, but this was lower compared to when PspA was encapsulated in PLGA/HCl-CS NPs, which also stimulated CD40+ and MHC II (I-A/I-E)+ cells. Despite no differences in IgG being observed between immunized animals, PGA-co-PDL/HCl-CS/adsorbed-PspA protected 83% of mice after lethal pneumococcal challenge, while 100% of mice immunized with PLGA/HCl-CS/encapsulated-PspA were protected. Therefore, this formulation is a promising vaccine strategy, which has beneficial properties for mucosal immunization and could potentially provide serotype-independent protection. Full article