Efficient Drug Delivery System Research Articles

Exploring current and emerging therapies for porphyrias.

Porphyrias are rare, mostly inherited disorders resulting from altered activity of specific enzymes in the haem synthesis pathway that lead to accumulation of pathway intermediates. Photocutaneous symptoms occur when excess amounts of photoreactive porphyrins circulate in the blood to the skin, whereas increases in potentially neurotoxic porphyrin precursors are associated with neurovisceral symptoms. Current therapies are suboptimal and their mechanisms are not well established. As described here, emerging therapies address underlying disease mechanisms by introducing a gene, RNA or other specific molecule with the potential to cure or slow progression of the disease. Recent progress in nanotechnology and nanoscience, particularly regarding particle design and formulation, is expanding disease targets. More secure and efficient drug delivery systems have extended our toolbox for transferring specific molecules, especially into hepatocytes, and led to proof-of-concept studies in animal models. Repurposing existing drugs as molecular chaperones or haem synthesis inhibitors is also promising. This review summarizes key examples of these emerging therapeutic approaches and their application for hepatic and erythropoietic porphyrias.

Organ-on-a-Chip Approach for Accelerating Blood-Brain Barrier Nanoshuttle Discovery.

Organ-on-a-chip, which recapitulates the dynamics of in vivo vasculature, has emerged as a promising platform for studying organ-specific vascular beds. However, its practical advantages in identifying vascular-targeted drug delivery systems (DDS) over traditional in vitro models remain underexplored. This study demonstrates the reliability and efficacy of the organ-on-a-chip in screening efficient DDS by comparing its performance with that of a conventional transwell, both designed to simulate the blood-brain barrier (BBB). The BBB nanoshuttles discovered through BBB Chip-based screening demonstrated superior functionality in vivo compared to those identified using transwell methods. This enhanced effectiveness is attributed to the BBB Chip's accurate replication of the structure and dynamics of the endothelial glycocalyx, a crucial protective layer within blood vessels, especially under shear stress. This capability of the BBB Chip has enabled the identification of molecular shuttles that efficiently exploit the endothelial glycocalyx, thereby enhancing transendothelial transport efficacy. Our findings suggest that organ-on-a-chip technology holds considerable promise for advancing research in vascular-targeted DDS due to its accurate simulation of molecular transport within endothelial systems.

Novel Drug Delivery Systems: An Important Direction for Drug Innovation Research and Development.

The escalating demand for enhanced therapeutic efficacy and reduced adverse effects in the pharmaceutical domain has catalyzed a new frontier of innovation and research in the field of pharmacy: novel drug delivery systems. These systems are designed to address the limitations of conventional drug administration, such as abbreviated half-life, inadequate targeting, low solubility, and bioavailability. As the disciplines of pharmacy, materials science, and biomedicine continue to advance and converge, the development of efficient and safe drug delivery systems, including biopharmaceutical formulations, has garnered significant attention both domestically and internationally. This article presents an overview of the latest advancements in drug delivery systems, categorized into four primary areas: carrier-based and coupling-based targeted drug delivery systems, intelligent drug delivery systems, and drug delivery devices, based on their main objectives and methodologies. Additionally, it critically analyzes the technological bottlenecks, current research challenges, and future trends in the application of novel drug delivery systems.

Ti3C2 (MXene), an advanced carrier system: role in photothermal, photoacoustic, enhanced drugs delivery and biological activity in cancer therapy.

In the realm of healthcare and the advancing field of medical sciences, the development of efficient drug delivery systems become an immense promise to cure several diseases. Despite considerable advancements in drug delivery systems, numerous challenges persist, necessitating further enhancements to optimize patient outcomes. Smart nano-carriers, for instance, 2D sheets nano-carriers are the recently emerging nanosheets that may garner attention for targeted delivery of bioactive compounds, drugs, and genes to kill cancer cells. Within these advancements, Ti3C2TX-MXene, characterized as a two-dimensional transition metal carbide, has surfaced as a prominent intelligent nanocarrier within nanomedicine. Its noteworthy characteristics facilitated it as an ideal nanocarrier for cancer therapy. In recent advancements in drug delivery research, Ti3C2TX-MXene 2D nanocarriers have been designed to release drugs in response to specific stimuli, guided by distinct physicochemical parameters. This review emphasized the multifaceted role of Ti3C2TX-MXene as a potential carrier for delivering poorly hydrophilic drugs to cancer cells, facilitated by various polymer coatings. Furthermore, beyond drug delivery, this smart nanocarrier demonstrates utility in photoacoustic imaging and photothermal therapy, further highlighting its significant role in cellular mechanisms.

A Biodegradable Nano-Drug Delivery Platform for Co-Delivery of Minocycline and Chitosan to Achieve Efficient and Safe Non-Surgical Periodontitis Therapy.

Mesoporous silica nanoparticles (MSN) are widely used as ideal nanovehicles for the delivery of chemotherapeutic drugs. However, the balance between high anti-periodontitis activity and low biotoxicity has been challenging to maintain in most relevant studies owing to the slow degradation of silica in living organisms. In this study, -responsive hydroxyapatite (HAP) was doped into the MSN skeleton, and the chemotherapeutic drug minocycline hydrochloride (MH) was loaded into the pores of MSN, forming a negatively charged drug delivery system. Cationic chitosan (COS) is a biodegradable material with high antibacterial performance and good biosafety. In this study, COS was immobilized on the surface of the drug-loaded particles through stable charge interaction to construct a composite drug delivery system (MH@MSNion@COS). In vitro and cellular experiments demonstrated effective degradation of the nanocarrier system and synchronized controlled release of the drug. Notably, compared with single MH administration, this system, in which MH and COS jointly regulated the expression levels of periodontitis- associated inflammatory factors (TNF-α, IL-6, IL-1β, and iNOS), better inhibited the progress of periodontitis and induced tissue regeneration without showing significant toxic side effects in cells. This system provides a promising strategy for the design of intelligent, efficient, and safe anti-periodontitis drug delivery systems.

Effects of hypromellose acetate succinate on recrystallization inhibition, miscibility, and dissolution enhancement of baloxavir marboxil solid dispersions

Solid dispersions (SDs) have emerged as a promising strategy to enhance the solubility and bioavailability of poorly soluble active pharmaceutical ingredients. However, SDs tend to recrystallize unless suitable excipients are utilized. This study aimed to facilitate the rational selection of polymers and formulation design by evaluating the impact of various polymers on the miscibility, and phase behavior of SDs using baloxavir marboxil (BXM) with a high crystallization tendency as a model drug. Meanwhile, the effects of these polymers on the solubility enhancement and recrystallization inhibition were also assessed. The results indicated that the miscibility limit of BXM for HPMCAS was around 40 % drug loading (DL), whereas for PVP, PVPVA, and HPMC approximately 20 % DL. The BXM-HPC system exhibited limited miscibility with DL of 10 % or higher. BXM SDs based on various polymers exhibited varying degrees of spontaneous phase separation once DL exceeded the miscibility limit. Interestingly, a correlation was discovered between the phase separation behavior and the ability of the polymer to inhibit recrystallization. BXM-HPMCAS SDs exhibited optimal dissolution performance, compared with other systems. In conclusion, the physicochemical properties of polymers significantly influence BXM SDs performance and the BXM-HPMCAS SDs might promote an efficient and stable drug delivery system.

Antioxidant Carbon Dots Nanozyme Loaded in Thermosensitive in situ Hydrogel System for Efficient Dry Eye Disease Treatment.

Dry eye disease (DED) is a multifactorial ocular surface disease with a rising incidence. Therefore, it is urgent to construct a reliable and efficient drug delivery system for DED treatment. In this work, we loaded C-dots nanozyme into a thermosensitive in situ gel to create C-dots@Gel, presenting a promising composite ocular drug delivery system to manage DED. This composite ocular drug delivery system (C-dots@Gel) demonstrated the ability to enhance adherence to the corneal surface and extend the ocular surface retention time, thereby enhancing bioavailability. Furthermore, no discernible ocular surface irritation or systemic toxicity was observed. In the DED mouse model induced by benzalkonium chloride (BAC), it was verified that C-dots@Gel effectively mitigated DED by stabilizing the tear film, prolonging tear secretion, repairing corneal surface damage, and augmenting the population of conjunctival goblet cells. Compared to conventional dosage forms (C-dots), the C-dots@Gel could prolong exhibited enhanced retention time on the ocular surface and increased bioavailability, resulting in a satisfactory therapeutic outcome for DED.

Biosynthesis and characterization of curcumin loaded CdO-SiO2@chitosan nanocomposite: Multifunctional agent for enhanced drug delivery vehicles for cancer therapy

Curcumin, a potent and extensively utilized cancer chemotherapeutic agent, faces limitations due to dose-dependent cardiotoxicity as its cumulative side effect. To surmount this challenge, a novel drug delivery system based on the biosynthesis of a cadmium oxide and silicon dioxide nanocomposite (CdO-SiO2-NC) has been developed. In this research, we have successfully synthesized innovative agents designed for an efficient drug delivery system, known as CdO-SiO2@CS-CUR-NC. A comprehensive characterization of this CdO-SiO2@CS-CUR-NC included an evaluation of the composition, chemical structure and morphology. The outcomes of assays focusing on inhibiting bacterial growth demonstrated significant efficacy in curbing bacterial proliferation within the concentration range of 50–100 µg/mL. This inhibitory effect was primarily attributed to the construction of reactive oxygen species (ROS). Furthermore, CdO-SiO2@CS-CUR-NC displayed noteworthy anti-inflammatory properties, evident from an observed to IC50 value of 25.12 µg/mL in human red blood cells. These outcomes suggest the possibility of this nanocomposite being used as an effective anti-inflammatory agent. Additionally, investigations into its cytotoxicity revealed a dose-dependent anti-cancer impact of the CdO-SiO2-NC across a variety of human cancer cell lines. The pronounced cytotoxicity on A549 cancer cells was particularly remarkable, where the IC50 value was measured as 31.10 µg/mL. The versatility of CdO-SiO2@CS-CUR-NC, encompassing antibacterial activity, anti-inflammatory as well as anticancer attributes, presents a auspicious avenue for further exploration. Particularly noteworthy is the potential application of CdO-SiO2@CS-CUR-NC as a novel anticancer agent in the field of lung cancer treatment. This research not only contributes to our comprehension of nanoscale interventions but also propels the potential roles of nanotechnology within the realm of pharmaceuticals.

Optimization of Dendritic Polypeptide Delivery System for Antisense Antibacterial Agents Targeting ftsZ.

There is an urgent requirement for a novel treatment strategy for drug-resistant Staphylococcus aureus (S. aureus) infection. Antisense antimicrobials are promising antimicrobials, and efficient drug delivery systems are necessary for the further development of antisense antimicrobials. To develop new antisense drugs and further improve delivery efficiency and safety, we designed and screened new antisense sequences and optimized dendritic polypeptide nanoparticles (DP-AD) discovered in previous studies. The N/P ratio is optimized from 8:1 to 6:1, and the positive charge number of the optimized DP-AD is studied comprehensively. The results show that the N/P ratio and positive charge number have no significant effect on the particle size distribution and transport efficiency of DP-AD. Reducing the N/P ratio can significantly reduce the cytotoxicity of DP-AD, but it does not affect its delivery efficiency and antibacterial activity. However, in drug-resistant strains, the antibacterial activity of DP-AD76:1 with 10 positive charges is higher than that of DP-AD86:1 with 8 positive charges. Our research discovered a novel ASOs targeting ftsZ and concluded that DP-AD76:1 with 10 positive charges was the optimal choice at the current stage, which provided a promising strategy for the treatment of drug-resistant S. aureus.

T Cell and Natural Killer Cell Membrane-Camouflaged Nanoparticles for Cancer and Viral Therapies.

Extensive research has been conducted on the application of nanoparticles in the treatment of cancer and infectious diseases. Due to their exceptional characteristics and flexible structure, they are classified as highly efficient drug delivery systems, ensuring both safety and targeted delivery. Nevertheless, nanoparticles still encounter obstacles, such as biological instability, absence of selectivity, recognition as unfamiliar elements, and quick elimination, which restrict their remedial capacity. To surmount these drawbacks, biomimetic nanotechnology has been developed that utilizes T cell and natural killer (NK) cell membrane-encased nanoparticles as sophisticated methods of administering drugs. These nanoparticles can extend the duration of drug circulation and avoid immune system clearance. During the membrane extraction and coating procedure, the surface proteins of immunological cells are transferred to the biomimetic nanoparticles. Such proteins present on the surface of cells confer several benefits to nanoparticles, including prolonged circulation, enhanced targeting, controlled release, specific cellular contact, and reduced in vivo toxicity. This review focuses on biomimetic nanosystems that are derived from the membranes of T cells and NK cells and their comprehensive extraction procedure, manufacture, and applications in cancer treatment and viral infections. Furthermore, potential applications, prospects, and existing challenges in their medical implementation are highlighted.

Rational Design of Coordination Polymers Composited Hollow Multishelled Structures for Drug Delivery.

Multifunctional drug delivery systems (DDS) are in high demand for effectively targeting specific cells, necessitating excellent biocompatibility, precise release mechanisms, and sustained release capabilities. The hollow multishelled structure (HoMS) presents a promising solution, integrating structural and compositional design for efficient DDS development amidst complex cellular environments. Herein, starting from a Fe-based metal-organic framework (MOF), amorphous coordination polymers (CP) composited HoMS with controlled shell numbers are fabricated by balancing the rate of MOF decomposition and shell formation. Fe-CP HoMS loaded with DOX is utilized for synergistic chemotherapy and chemodynamic therapy, offering excellent responsive drug release capability (excellent pH-triggered drug release 82% within 72h at pH 5.0 solution with doxorubicin (DOX) loading capacity of 284mg g-1). In addition to its potent chemotherapy attributes, Fe-CP-HoMS possesses chemodynamic therapy potential by continuously catalyzing H2O2 to generate ·OH species within cancer cells, thus effectively inhibiting cancer cell proliferation. DOX@3S-Fe-CP-HoMS, at a concentration of 12.5µg mL-1, demonstrates significant inhibitory effects on cancer cells while maintaining minimal cytotoxicity toward normal cells. It is envisioned that CP-HoMS could serve as an effective and biocompatible platform for the advancement of intelligent drug delivery systems in the realm of cancer therapy.

Conformational analysis and spectroscopic properties of antichagasic nifurtimox

Considering the health relevance of Chagas' disease, recent research efforts have focused on developing more efficient drug delivery systems containing nifurtimox (NFX). This paper comprehensively investigates NFX through conformational analysis and spectroscopic characterization. Using a conformer-rotamer ensemble sampling tool (CREST-xtb), five distinct conformers of NFX were sampled within a 3.0 kcal mol−1 relative energy window. Subsequently, such structures were used as inputs for geometry optimization by density functional theory (DFT) at B3LYP-def2-TZVP level of theory. Notably, harmonic vibrational frequencies were calculated to establish an in-depth comparison with experimental results and existing literature for the NFX or similar molecules and functional groups, thereby achieving a widely reasoned assignment of the mid-infrared band absorptions for the first time. Moreover, UV–VIS spectra of NFX were obtained in several solvents, enabling the determination of the molar absorptivity coefficient for the two electronic transitions observed for NFX. Among the aprotic solvents, a bathochromic effect was observed in the function of the dielectric constants. Furthermore, a hypochromic effect was observed when the drug was dissolved in protic solvents. These findings offer crucial support for new drug delivery systems containing NFX while demonstrating the potential of spectrophotometric studies in establishing quality control assays for NFX drug products.

Aptamer-modified Nanocarrier(s) for the Management of Prostate Cancer

Abstract: Prostate cancer remains a significant global health concern, necessitating the development of innovative therapeutic approaches. This editorial provides an overview of the current state of research on aptamer-modified nanocarriers as a novel strategy for prostate cancer therapy. Aptamers, known for their high specificity and affinity, have drawn much attention in both research and the pharmaceutical industry. The Systematic Evolution of Ligands by the Exponential Enrichment (SELEX) technique has enabled the development of aptamers that can selectively bind to target ligands based on their unique three-dimensional structures. Notably, the A10 aptamer, modified to target PSMA (Prostate-Specific Membrane Antigen), has demonstrated strong binding affinity and specificity to prostate cancer cells, offering promise as an efficient drug-delivery system. Additionally, biosensors, like the innovative apta-sensor targeting MUC1, have utilized aptamers to detect cancer through electrochemical signals. Additionally, aptamers have improved the pharmacological attributes of chemotherapeutic agents for prostate cancer treatment. Aptamer-- mediated drug delivery has offered enhanced drug delivery, targeting, cellular uptake, and minimizing side effects.

Infection‐responsive polysaccharide‐based drug‐loaded nano‐assembly for dual‐modal treatment against drug‐resistant bacterial lung infection

AbstractThe escalating issue of lung infections induced by multi‐drug resistant (MDR) bacteria is threatening human health. Thus, the development of efficient drug delivery systems is essential to eliminate MDR bacterial lung infections effectively. Herein, we designed inhalable drug‐loaded nano‐assemblies by the electrostatic interaction between negatively charged sodium alginate and a positively charged antibacterial polymer, quaternized polyethyleneimine (QPEI‐C6), as well as a kind of typical antibiotic for therapy of lung infection, azithromycin (AZT). By adjusting the feed ratios, we optimized the size of the nano‐assembly to approximately 200 nm (STQ12), which was beneficial for penetration through the mucus layer and biofilm. In the slightly acidic environment of the infected site, the nano‐assembly could dissemble responsively and release AZT and QPEI‐C6. Because of the combined bactericidal effect, STQ12 exhibited high bactericidal efficiency against MDR bacteria. In animal experiments, STQ12 showed notable efficacy against MDR bacterial lung infection. Gene transcriptomic results showed that the main effects of STQ12 against bacteria were through influencing the bacterial cell components and metabolic processes, and affecting their growth and reproduction. This work provides a promising strategy to treat MDR bacterium‐induced lower respiratory tract infections.

Pharmaceutical Applications of Biomass Polymers: Review of Current Research and Perspectives.

Polymers derived from natural biomass have emerged as a valuable resource in the field of biomedicine due to their versatility. Polysaccharides, peptides, proteins, and lignin have demonstrated promising results in various applications, including drug delivery design. However, several challenges need to be addressed to realize the full potential of these polymers. The current paper provides a comprehensive overview of the latest research and perspectives in this area, with a particular focus on developing effective methods and efficient drug delivery systems. This review aims to offer insights into the opportunities and challenges associated with the use of natural polymers in biomedicine and to provide a roadmap for future research in this field.

Meta-analysis of nano-phytosomes: unleashing the potential of plant-derived compounds for advancing cancer therapy

Nano-phytosomes are considered as an efficient drug delivery system for phytochemicals. Phytosomes enhance stability and significantly improves phytochemicals bioavailability and therapeutic efficacy. Thorough meta-analysis of 93 articles, phytochemical versus phytosomes size, charge, polydispersity index (PDI) and IC50 values were investigated. Multivariate Analysis of Covariance revealed significant phytochemicals type effects, even when accounting for cancer cell type and phospholipid type as covariates. Least Significant Difference (LSD) post hoc tests described unique attributes among various phytosomes. Flavonoid-based phytosomes exhibited larger particle sizes than others. In contrast, terpenoid-based phytosomes displayed significantly lower charges. Flavonoids demonstrated higher poly dispersity index (PDI) values than alkaloids and polyphenols. Alkaloids exhibited more extensive PDI values, while polyphenols had lower PDI values than terpenoids. Furthermore, flavonoid-containing nanoparticles exhibited higher IC50 values than terpenoids. In conclusion, nano-phytosomes offer promising prospects for revolutionising drug delivery methodologies and advancing the development of innovative therapeutic solutions in the domain of cancer therapy.

Empowering Naringin's Anti-Inflammatory Effects through Nanoencapsulation.

Abundant in citrus fruits, naringin (NAR) is a flavonoid that has a wide spectrum of beneficial health effects, including its anti-inflammatory activity. However, its use in the clinic is limited due to extensive phase I and II first-pass metabolism, which limits its bioavailability. Thus, lipid nanoparticles (LNPs) were used to protect and concentrate NAR in inflamed issues, to enhance its anti-inflammatory effects. To target LNPs to the CD44 receptor, overexpressed in activated macrophages, functionalization with hyaluronic acid (HA) was performed. The formulation with NAR and HA on the surface (NAR@NPsHA) has a size below 200 nm, a polydispersity around 0.245, a loading capacity of nearly 10%, and a zeta potential of about 10 mV. In vitro studies show the controlled release of NAR along the gastrointestinal tract, high cytocompatibility (L929 and THP-1 cell lines), and low hemolytic activity. It was also shown that the developed LNPs can regulate inflammatory mediators. In fact, NAR@NPsHA were able to decrease TNF-α and CCL-3 markers expression by 80 and 90% and manage to inhibit the effects of LPS by around 66% for IL-1β and around 45% for IL-6. Overall, the developed LNPs may represent an efficient drug delivery system with an enhanced anti-inflammatory effect.

Potential of Exosomes as Therapeutics and Therapy Targets in Cancer Patients

After an initial positive response to chemotherapy, cancer patients often acquire chemoresistance and tumor relapse, which makes cancer one of the most lethal diseases worldwide. Exosomes are essential mediators of cell-to-cell communication by delivering their cargo, such as proteins, RNAs and DNA, from cell to cell. They participate in cancer progression, metastasis, immune response and therapy resistance. Their ability to shuttle between cells makes them efficient drug delivery systems. As drug transporters, they provide novel strategies for cancer therapy by advancing targeted drug therapy and improving the therapeutic effects of anti-cancer medications. In this review, a comprehensive overview of the potential of exosomes as therapeutic agents and targeted molecules in the treatment of cancer patients is given. The current challenges of preparation of exosomes loaded with drugs and delivering them to the recipient tumor cells as well as a consequent exosome-mediated cancer therapy are also discussed.

Physical characterization and bioavailability assessment of 5-fluorouracil-based nanostructured lipid carrier (NLC): In vitro drug release, Hemolysis, and permeability modulation.

5-Fluorouracil (5-FU) is an anticancer agent belonging to BCS Class III that exhibits poor release characteristics and low retention in the biological system. The main objective of this investigation was to develop a drug delivery system, i.e., Nanostructure Lipid Carriers (NLCs) loaded with 5-FU to prolong its biological retention through 5-FU-loaded NLCs (5-FUNLC) were designed to manipulate physicochemical characteristics and assessment of in vitroandin vivoperformance. The developed NLCs underwent comprehensive characterization, including assessments for particle size, zeta potential, morphological evaluation, and FT-IR spectroscopy. Additionally, specific evaluations were conducted for 5-FUNLCs, encompassing analyses for encapsulation efficiency of the drug, release characteristics in PBS at pH 6.8, and stability study. The lipophilic character of 5-FUNLC was confirmed through the measurement of the partition coefficient (log P). 5-FUNLCs were observed as spherical-shaped particles with a mean size of 300 ± 25nm. The encapsulation efficiency was determined to be 89%, indicating effective drug loading within the NLCs. Furthermore, these NLCs exhibited a sustained release nature lasting up to 3-4h, indicating their potential for controlled drug release over time. Lipid components were biocompatible with the 5-FU to determine thermal transition temperature and show good stability for 30days. Additionally,an in vitrohemolysis study that confirmed the system did not cause any destruction to the RBCs during intravenous administration. The drug's gut permeability was assessed utilizing the optimized 5-FUNLC (F2) in comparison to 5-FU through the intestine or gut sac model (in the apical to basolateral direction, A → B). The permeability coefficient was measured as 4.91 × 10-5cm/h with a significant difference. Additionally, the antioxidant potential of the NLCs was demonstrated through the DPPH method. The NLCs' performance was further assessed throughin vivopharmacokinetic studies on Wistar Rats, resulting in a 1.5-fold enhancement in their activity compared to free 5-FU. These NLCs offer improved drug solubility and sustained release, which collectively contribute to enhanced therapeutic outcomes and modulate bioavailability. The study concludes by highlighting the potential of 5-FUNLC as an innovative and efficient drug delivery system. The findings suggest that further preclinical investigations are warranted, indicating a promising avenue for the development of more effective and well-tolerated treatments for cancer.

Preparation of Compound Salvia miltiorrhiza-Blumea balsamifera Nanoemulsion Gel and Its Effect on Hypertrophic Scars in the Rabbit Ear Model.

Hypertrophic scars (HS) still remain an urgent challenge in the medical community. Traditional Chinese medicine (TCM) has unique advantages in the treatment of HS. However, due to the natural barrier of the skin, it is difficult for the natural active components of TCM to more effectively penetrate the skin and exert therapeutic effects. Therefore, the development of an efficient drug delivery system to facilitate enhanced transdermal absorption of TCM becomes imperative for its clinical application. In this study, we designed a compound Salvia miltiorrhiza-Blumea balsamifera nanoemulsion gel (CSB-NEG) and investigated its therapeutic effects on rabbit HS models. The prescription of CSB-NEG was optimized by single-factor, pseudoternary phase diagram, and central composite design experiments. The results showed that the average particle size and PDI of the optimized CSB-NE were 46.0 ± 0.2 nm and 0.222 ± 0.004, respectively, and the encapsulation efficiency of total phenolic acid was 93.37 ± 2.56%. CSB-NEG demonstrated excellent stability and skin permeation in vitro and displayed a significantly enhanced ability to inhibit scar formation compared to the CSB physical mixture in vivo. After 3 weeks of CSB-NEG treatment, the scar appeared to be flat, pink, and flexible. Furthermore, this treatment also resulted in a decrease in the levels of the collagen I/III ratio and TGF-β1 and Smad2 proteins while simultaneously promoting the growth and remodeling of microvessels. These findings suggest that CSB-NEG has the potential to effectively address the barrier properties of the skin and provide therapeutic benefits for HS, offering a new perspective for the prevention and treatment of HS.