Hydroxypropyltrimethyl Ammonium Chloride Chitosan Research Articles

The initial application of conch-shell hydroxyapatite and HACC as functional filler in PMMA bone cement

In this study, we acquired conch-shell Hydroxyapatite (cHA)with a mean size of 99.41 nm using a microwave-assisted method, and hydroxypropyl trimethyl ammonium chloride chitosan (HACC) with a molecular weight of 41 kDa was synthesized from deacetylated chitosan. These two additives were added to plain PMMA bone cement, improving its biological activity. It was shown that the addition of cHA and HACC balanced the mechanical performance and porosity of the implant, improving its biocompatibility with mouse pre-osteoblasts (MC3T3-E1). A composite cement with 30 wt% cHA and 0.5 wt% HACC significantly enhanced mineralization efficiency, protein adsorption, and alkaline phosphatase (ALP) activity.

Effects of Chitosan and Cellulose Derivatives on Sodium Carboxymethyl Cellulose-Based Films: A Study of Rheological Properties of Film-Forming Solutions.

Bio-based packaging materials and efficient drug delivery systems have garnered attention in recent years. Among the soluble cellulose derivatives, carboxymethyl cellulose (CMC) stands out as a promising candidate due to its biocompatibility, biodegradability, and wide resources. However, CMC-based films have limited mechanical properties, which hinders their widespread application. This paper aims to address this issue by exploring the molecular interactions between CMC and various additives with different molecular structures, using the rheological method. The additives include O-carboxymethylated chitosan (O-CMCh), N-2-hydroxypropyl-3-trimethylammonium-O-carboxymethyl chitosan (HTCMCh), hydroxypropyltrimethyl ammonium chloride chitosan (HACC), cellulose nanocrystals (CNC), and cellulose nanofibers (CNF). By investigating the rheological properties of film-forming solutions, we aimed to elucidate the influencing mechanisms of the additives on CMC-based films at the molecular level. Various factors affecting rheological properties, such as molecular structure, additive concentration, and temperature, were examined. The results revealed that the interactions between CMC and the additives were dependent on the charge of the additives. Electrostatic interactions were observed for HACC and HTCMCh, while O-CMCh, CNC, and CNF primarily interacted through hydrogen bonds. Based on these rheological properties, several systems were selected to prepare the films, which exhibited excellent transparency, wettability, mechanical properties, biodegradability, and absence of cytotoxicity. The desirable characteristics of these selected films demonstrated the strong biocompatibility between CMC and chitosan and cellulose derivatives. This study offers insights into the preparation of CMC-based food packaging materials with specific properties.

Electrospun chitosan-based nanofibers loading tea tree oil for fresh salmon fillet shelf-life extension.

Bioactive packaging can improve the shelf-life of food products and enhance consumer health. It can also alleviate environmental stress on the planet by reducing food waste. Here, the electrospinning of tea tree oil-loaded 2-hydroxypropyltrimethyl ammonium chloride chitosan nanofibers was investigated. The fabricated nanofiber films were characterized by scanning electron microscopy, thermal gravimetric analysis, Fourier transform infrared spectroscopy, and contact angle meter analysis. The prepared nanofibers have a well-defined diameter of about 200nm and a smooth shape. They have good antibacterial properties against Staphylococcus aureus and Escherichia coli in vitro. Tea tree oil-loaded chitosan-based nanofibers were found to be effective in delaying spoilage and extending the shelf life of salmon by sensory evaluation, texture analysis, color, total viable counts, thiobarbituric acid, and total volatile basic nitrogen during storage in the freshness experiments, thus indicating their health benefits in bioactive packaging.

20(R)-ginsenoside Rg3-loaded polyurethane/marine polysaccharide based nanofiber dressings improved burn wound healing potentials

The management of deep burn injuries is extremely challenging, ascribed to their delayed wound healing rate, susceptibility for bacterial infections, pain, and increased risk of hypertrophic scarring. In our current investigation, a series of composite nanofiber dressings (NFDs) based on polyurethane (PU) and marine polysaccharides (i.e., hydroxypropyl trimethyl ammonium chloride chitosan, HACC and sodium alginate, SA) were accomplished by electrospinning and freeze-drying protocols. The 20(R)-ginsenoside Rg3 (Rg3) was further loaded into these NFDs to inhibit the formation of excessive wound scars. The PU/HACC/SA/Rg3 dressings showed a sandwich-like structure. The Rg3 was encapsulated in the middle layers of these NFDs and slowly released over 30 days. The PU/HACC/SA and PU/HACC/SA/Rg3 composite dressings demonstrated superior wound healing potentials over other NFDs. These dressings also displayed favorable cytocompatibility with keratinocytes and fibroblasts and could dramatically accelerate epidermal wound closure rate following 21 days of the treatment of a deep burn wound animal model. Interestingly, the PU/HACC/SA/Rg3 obviously reduced the excessive scar formation, with a collagen type I/III ratio closer to the normal skin. Overall, this study represented PU/HACC/SA/Rg3 as a promising multifunctional wound dressing, which promoted the regeneration of burn skins and attenuated scar formation.

Preparation and characterization of antibacterial, antioxidant, and biocompatible p-coumaric acid modified quaternized chitosan nanoparticles

To fabricate multifunctional nanoparticles (NPs) based on chitosan (CS) derivative, we first prepared quaternized CS (2-hydroxypropyltrimethyl ammonium chloride CS, HTCC) via a one-step approach, then synthesized p-coumaric acid (p-CA) modified HTCC (HTCC-CA) for the first time through amide reaction, and finally fabricated a series of NPs (HTCC-CA NPs) using HTCC-CAs with different substitution degrees and sodium tripolyphosphate (TPP) by ionic gelation. Newly-prepared HTCC and HTCC-CAs were characterized by FT-IR, 1H NMR, elemental analysis (EA), full-wavelength UV scanning, silver nitrate titration, and Folin-Ciocalteu methods. DLS and TEM results demonstrated that three selected HTCC-CA NPs had moderate size (< 350 nm), good dispersion (PDI < 0.4), and positive zeta potential (11–20 mV). The HTCC-CA NPs had high antibacterial activity against six bacterial strains, and the minimum inhibitory concentration (MIC) values were almost the same as the minimum bactericidal concentration (MBC) values (250–1000 μg/mL). Also, the HTCC-CA NPs had good antioxidation (radical scavenging ratio > 65 %) and low cytotoxicity (relative cell viability >80 %) to the tested cells. Totally, HTCC-CA NPs with high antibacterial activity, great antioxidation, and low cytotoxicity might serve as new biomedical materials for promoting skin wound healing.

Inhibition of Staphylococcus aureus biofilms by poly-L-aspartic acid nanoparticles loaded with Litsea cubeba essential oil

Staphylococcus aureus (S. aureus) biofilms contamination on various food-contacting surfaces is considered a significant threat in the field of food. Poly-L-aspartic acid (PASP) was proven to damage biofilm by affecting bacterial adhesion, metabolic activity, and extracellular polymeric substances in this study. Especially for eDNA, its generation was reduced by 49.4 %. After treatment with 5 mg/mL of PASP, the number of S. aureus in the biofilm at different growth stages decreased by 1.20–1.68 log CFU/mL. The nanoparticles prepared by PASP and hydroxypropyl trimethyl ammonium chloride chitosan were used to embed LC-EO (EO@PASP/HACCNPs). The results indicated that the particle size of the optimized nanoparticles was 209.84 nm with an encapsulation rate of 70.28 %. Compared to LC-EO alone, EO@PASP/HACCNPs had more significant permeation and dispersion effects on biofilms and possessed long-lasting anti-biofilm activity. For the biofilm grown for 72 h, the population of S. aureus in the EO@PASP/HACCNPs-treated biofilm was additionally reduced by 0.63 log CFU/mL compared with the LC-EO-treated group. EO@PASP/HACCNPs were also applied to different food-contacting materials. The lowest inhibition rate of EO@PASP/HACCNPs on S. aureus biofilm still reached 97.35 %. The sensory properties of the chicken breast were not affected by EO@PASP/HACCNPs.

Quaternary ammonium salt functionalized HA as an antibacterial and osteogenic coating for bone implants

The construction of hydroxyapatite (HA) antibacterial coating on titanium surface is one of the current research hot topics. Natural antimicrobial agents can promote bone production while sterilizing. In this paper, Polypyrrole (PPy) is driven in situ by pulsed electrochemical deposition. Under the oxidation potential, the amino group of Pyrrole (Py) monomer interacts with PO43− and Dexamethasone root ion(Dex−) in the electrolyte through electrostatic interaction. The phenolic hydroxyl group chitosan quaternary ammonium salt (2-hydroxypropyltrimethyl ammonium chloride chitosan, HTCC) interacts with N atom of the amino group on Py and forms hydrogen bonds to assist Py in regulating Dexamethasone (Dex) the drug. While under the reduction potential, OH− is produced near the working electrode to promote the generation of HA, and finally forms the PPy@HA/Dex/HTCC composite coating. The study show that the composite coating is spherical nanoparticles with uniform distribution, and the regulation effect of PPy reduces the release rate of Ca2+ and Dex− from the coating, making it release smoothly and slowly. The antibacterial ratio of the composite coating against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) reaches 100%, the osteoblasts and vascular endothelial cells proliferate well on the surface of the composite coating in vitro. Besides, the composite coating can induce the growth of apatite, proving that it has good bioactivity.

Converting Acellular Dermal Matrix into On-Demand Versatile Skin Scaffolds by a Balanceable Crosslinking Approach for Integrated Infected Wounds Therapy.

Ideal tissue-engineered skin scaffolds should possess integrated therapeutic effects and multifunctionality, such as broad-spectrum antibacterial properties, adjustable mechanical properties, and bionic structure. Acellular dermal matrix (ADM) has been broadly used in many surgical applications as an alternative treatment to the "gold standard" tissue transplantation. However, insufficient broad-spectrum antibacterial and mechanical properties for therapeutic efficacy limit the practical clinical applications of ADM. Herein, a balanceable crosslinking approach based on oxidized 2-hydroxypropyltrimethyl ammonium chloride chitosan (OHTCC) was developed for converting ADM into on-demand versatile skin scaffolds for integrated infected wounds therapy. Comprehensive experiments show that different oxidation degrees of OHTCC have significative influences on the specific origins of OHTCC-crosslinked ADM scaffolds (OHTCC-ADM). OHTCC with an oxidation degree of about 13% could prosperously balance the physiochemical properties, antibacterial functionality, and cytocompatibility of the OHTCC-ADM scaffolds. Owing to the natural features and comprehensive crosslinking effects, the proposed OHTCC-ADM scaffolds possessed the desirable multifunctional properties, including adjustable mechanical, degradable characteristics, and thermal stability. In vitro/in vivo biostudies indicated that OHTCC-ADM scaffolds own well-pleasing broad-spectrum antibacterial performances and play effectively therapeutic roles in treating infection, inhibiting inflammation, promoting angiogenesis, and promoting collagen deposition to enhance the infected wound healing. This study proposes a facile balanceable crosslinking approach for the design of ADM-based versatile skin scaffolds for integrated infected wounds therapy.

Advanced Mg2+/Li+ separation nanofiltration membranes by introducing hydroxypropyltrimethyl ammonium chloride chitosan as a co-monomer

In recent years, the global demand for lithium resources has been constantly rising thanks to the rapid development of the new energy industry. Nanofiltration (NF) membranes with positive charge could achieve high efficiency separation performance of magnesium ion (Mg2+)/ lithium ion (Li+), which provides a useful solution for the extraction and recovery of lithium resources from brine. In this work, hydroxypropyltrimethyl ammonium chloride chitosan (HACC) was introduced into the interfacial polymerization (IP) as co-monomer with piperazine (PIP) to react with trimesoyl chloride (TMC) for preparing positively charged NF membranes. Based on the modulation of IP process by HACC, the thickness of the modified NF membrane separation layer reduced and the hydrophilicity increased, while the pore size had no obvious variation. In addition, the introduction of the quaternary ammonium group in HACC also increased the antibacterial properties of the NF membrane. The optimized NF-HACC-0.3 not only improved the separation factor significantly, but also increased the flux by 2 times compared with the original membrane. This strategy provides a new valuable idea and insight for the preparation and development of Mg2+/Li+ separation NF membranes.

Mucus adhesion vs. mucus penetration? Screening nanomaterials for nasal inhalation by MD simulation.

Nanocarrier-aided drug delivery techniques have improved the absorption and permeability of drugs in nose-to-brain delivery. However, the molecular properties of nanocarriers during the delivery process are of great interest; in particular, the characteristics when penetrating barriers in vivo are crucial for the screening and optimization of materials for nasal inhalation. In this study, we have focused on two types of delivery systems: mucoadhesive nanoparticles (MAPs) and mucopenetrating nanoparticles (MPPs); both have been widely used for mucosal delivery, although a method for selecting the more effective type of drug carriers for mucosal delivery has not been established. Molecular dynamics (MD) simulations were used to reveal the all-atom dynamic characteristics of the interaction between different delivery systems and the nasal mucus protein MUC5AC. Among the systems tested, hydroxypropyltrimethyl ammonium chloride chitosan (HTCC) had the strongest interaction with mucin, suggesting it had better mucoadhesive performance, and that it interacted with MUC5AC more strongly than unmodified chitosan. In contrast, the mucus-penetrating material polyethylene glycol-poly lactic acid-co-glycolic acid (PEG-PLGA), had almost no interaction with MUC5AC. The results of the MD simulations were verified by in vitro experiments on nanoparticles (NPs) and mucin binding. The drug delivery performance of the four types of NPs, analyzed by in vitro and ex vivo mucosal penetration, were all generally consistent with the properties of the material predicted from the MD simulation. These clues to the molecular mechanism of MAPs and MPPs may provide useful insight into the screening and optimization of nanomaterials suitable for nasal inhalation.

Preparation and application of coconut shell-based skeleton `1particles coupled with hydroxypropyltrimethyl ammonium chloride chitosan in sludge dewatering

Preparation and application of coconut shell-based skeleton `1particles coupled with hydroxypropyltrimethyl ammonium chloride chitosan in sludge dewatering

A Thermal and Enzymatic Dual-Stimuli Responsive DNA-Based Nanomachine for Controlled mRNA Delivery.

The extreme instability of mRNA makes the practical application of mRNA-based vaccines heavily rely on efficient delivery system and cold chain transportation. Herein, a DNA-based nanomachine, which achieves programmed capture, long-term storage without cryopreservation, and efficient delivery of mRNA in cells, is developed. The polythymidine acid (Poly-T) functionalized poly(N-isopropylacrylamide) (DNA-PNIPAM) is synthesized and assembled as the central compartment of the nanomachine. The DNA-PNIPAM nano-assembly exhibits reversible thermal-responsive dynamic property: when lower than the low critical solution temperature (LCST, ≈32 °C) of PNIPAM, the DNA-PNIPAM transforms into extension state to expose the poly-T, facilitating the hybridization with polyadenylic acid (Poly-A) tail of mRNA; when higher than LCST, DNA-PNIPAM re-assembles and achieves an efficient encapsulation of mRNA. It is remarkable that the DNA-PNIPAM nano-assembly realizes long-term storage of mRNA (≈7 days) at 37 °C. Biodegradable 2-hydroxypropyltrimethyl ammonium chloride chitosan is assembled on the outside ofDNA-PNIPAM to facilitate the endocytosis of mRNA, RNase-H mediating mRNA release occurs in cytoplasm, and efficient mRNA translation is achieved. This work provides a new disign principle of nanosystem for mRNA delivery.

Injectable self-healing chitosan-based POSS-PEG hybrid hydrogel as wound dressing to promote diabetic wound healing

Promoting the healing of diabetic wounds remains a major challenge in scientific research today. A star-like eight-arm cross-linker octafunctionalized POSS of benzaldehyde-terminated polyethylene glycol (POSS-PEG-CHO) was synthesized, and crosslinked with hydroxypropyltrimethyl ammonium chloride chitosan (HACC) via Schiff base reaction to obtain Chitosan-based POSS-PEG hybrid hydrogels. The designed composite hydrogels exhibited strong mechanical strength, injectability, excellent self-healing efficiency, good cytocompatibility and antibacterial properties. Furthermore, the composite hydrogels could accelerate cells migration and proliferation, as expected by remarkably promoting wound healing in diabetic mice. The wounds treated with the composite hydrogels displayed faster regeneration of epithelial tissue, fewer inflammatory cells, more collagen deposition and higher expression level of VEGF. Therefore, Chitosan-based POSS-PEG hybrid hydrogel has great application potential as a dressing for promoting the healing of diabetic wounds.

Fabrication of antibacterial Janus bandages with high wound healing performances by facile single-side electrospray PDMS coating

Bandages are widely utilized to cover local wounds. However, most bandages have limited capacities to promote wound healing, which may occasionally cause serious wound infections. Accordingly, herein, we demonstrated a facile electrospray method to fabricate an antibacterial Janus bandage that could simultaneously remove wound bed exudate and prevent wound infection. The advanced bandage was only composed of an adhesive strip and an antibacterial Janus cotton fabric, whose single side was controllably electrospray-coated with a thin polydimethylsiloxane coating. The Janus cotton fabric exhibited a high one-way transport index (R = 1068%), suggesting its appropriate directional liquid moisture transport ability, and excellent air permeability. Furthermore, in vitro experiments demonstrated that the advanced bandage had adequate biocompatibility and exhibited sustained release of hydroxypropyltrimethyl ammonium chloride chitosan, which considerably enhanced the proliferation of fibroblasts. As a proof-of-concept, this bandage was employed to drain the exudate from Staphylococcus aureus (S. aureus)-infected mice wounds and kill S. aureus in these wounds, which significantly accelerated wound healing. The simple fabrication process of unique bandage reveals it has considerable potential as a next-generation bandage for healing local wounds clinically.

Protective Effect of Composite Hydrogel Based on Hydroxypropyl Trimethylammonium Chloride Chitosan on Skin Photodamage

Long-term or excessive exposure to UV light can lead to sunburn, erythema, melanin deposition, inflammation, and even skin cancer. This study used composite hydrogels with N-2-hydroxypropyl trimethylammonium chloride chitosan (N-2-HACC) and hyaluronic acid (HA) as carriers. In addition, ellagic acid (EA) and proanthocyanidins (PC) as functionalized materials were prepared. The infrared results show that the N-2-HACC/HA/EA/PC hydrogel is formed by N-2-HACC connecting with HA by electrostatic interaction, and HA forms hydrogen bonds between EA and PC. The in vitro antioxidant results show that EA and PC have different clearance efficiency of DPPH and superoxide anion radicals at different pH values. Thus, they have complementary effects on antioxidant properties. The cumulative release results demonstrate that the hydrogels had an excellent slow-release rate at different pHs. The animal experiments reveal that N-2-HACC/HA/EA/PC could restore the consumption of antioxidant enzymes induced by UVB irradiation and inhibit matrix metalloproteinase 1. N-2-HACC/HA/EA/PC can inhibit UVB-induced histological damage, such as epidermal thickening, collagen fiber, and elastic fiber destruction. N-2-HACC/HA/EA/PC has a significant photoprotective effect by protecting the activities of superoxide dismutase, catalase, and glutathione peroxidase and inhibiting the activity of inflammatory factors. N-2-HACC/HA/EA/PC composite hydrogel system shows comprehensive performance. Its ability to scavenge free radicals may act as an antioxidant to protect mice from skin cancer.

An injectable, self-healing composite hydrogel with enhanced near-infrared photo-antibacterial therapeutic effects for accelerated wound healing

Antibacterial hydrogels with injectable and self-healing properties have attracted much attention in the field of wound dressings because they not only can prevent bacterial infections, but also meet the basic needs for wound healing. However, how to achieve high antibacterial efficacy and low drug resistance for hydrogels is still a challenge. Herein, an injectable, self-healing, near-infrared (NIR) photosensitive antibacterial hydrogel composed of CuS-grafted-curcumin (CuS@C) and carboxymethyl cellulose modified with aldehyde groups and hydroxypropyl trimethyl ammonium chloride chitosan is prepared for wound dressings. The p-n junction formed between curcumin and CuS promotes separation of electron-hole pairs, enhances the mobility of photogenerated charges, and destroys the conjugated structure of curcumin simultaneously consequently increasing the photocatalytic activity. CuS@C is immobilized and distributed uniformly in the hydrogel via the π-π conjugation ring. The hybrid hydrogel exhibits excellent antibacterial activity after irradiation with 808 NIR light for 10 min due to the enhanced photodynamic and photothermal antibacterial effects. In addition, the hybrid structure improves the biocompatibility of CuS and expedites infected-wound healing at a mild temperature of 45 ℃. This organic/inorganic hybrid is shown to be an excellent wound dressing for the treatment of bacterial-infected wounds.

Combination of natural polyanions and polycations based on interfacial complexation for multi-functionalization of wound dressings.

Multi-functionalization of wound dressings with natural polymers is meaningful and remains a challenge. The combination of natural polyanions and polycations appears to be a promising strategy. Still, its performances based on current layer-by-layer self-assembly or homogeneous complexation are mutable and limited. Herein, Ca2+-incorporated carboxymethyl cellulose (Ca/Na-CMC) and hydroxypropyltrimethyl ammonium chloride chitosan (HACC) are adopted as the model polyanion and polycation, respectively, to develop multi-functionalized dressings based on interfacial complexation. The dressings exhibit a multilayer structure composed of a polyanion layer (Ca/Na-CMC) for hemostasis and promotion of cell proliferation, a formed polyelectrolyte complex (PEC) layer for structural stability, and a polycation layer (HACC) for antibiosis. Compared to the dressing based on homogeneous complexation, the multilayer dressings show stronger moisture penetrability (around 1,150 g/m2/24 h), higher hemostatic activity, and higher antibacterial rate (up to 100%) and promoted effect on cell proliferation. An in vivo evaluation using a rat full-thickness skin defect model reveals that the multilayer dressings can accelerate wound healing in 2 weeks. Overall, owing to interfacial complexation resulting in separate layers, the performances of polyanions and polycations after combination are more predictable, and their biological functions can be effectively preserved. These findings not only support the extensive application of multilayer dressings but also offer an alternative strategy for multi-functionalizing wound dressings with natural polyanions and polycations.

Hydroxypropyltrimethyl Ammonium Chloride Chitosan Nanoparticles Coatings for Reinforcement and Concomitant Inhibition of Anionic Water-Sensitive Dyes Migration on Fragile Paper Documents.

The fragile paper is treated to improve the stability and appearance of the paper artifact, such as washing, lining, deacidification, and reinforcement. During the above treatments, paper documents inevitably make contact with water directly, leading to the appearance change, stability decrease, and migration or fading of anionic water-sensitive dyes, which are seriously harmful to information security. Herein, Hydroxypropyltrimethyl ammonium chloride chitosan (HACC) nanoparticles were employed for the reinforcement and concomitant inhibition of anionic water-sensitive dye migration on fragile paper. HACC nanoparticles were prepared through physical ball grinding method and characterized via LPSA, SEM, TEM, XRD and FTIR. To evaluate the protective potential of HACC nanoparticles coating, the chemical and mechanical properties of coated and uncoated papers were evaluated after dry heat and hygrothermal accelerated aging. Additionally, good color stability of anionic water-sensitive dyes was observed on the paper coated with HACC nanoparticles after lining technology. Finally, the interaction mechanism between the anionic water-sensitive dyes and HACC nanoparticles was analyzed using an ultraviolet spectrophotometer and FTIR. The as-proposed technique can provide technical support to improve the mechanical properties of fragile paper and enhance the anionic water-sensitive dyes stability in the aqueous phase.

Tannic acid/polyvinyl alcohol/2-hydroxypropyl trimethyl ammonium chloride chitosan double-network hydrogel with adhesive, antibacterial and biocompatible properties

Hydrogels have great potential for biomedical applications. However, there are still significant challenges in preparing biomass-based hydrogels with excellent adhesive, antibacterial and biocompatible properties. In this study, pure physically cross-linked tannic acid (TA)/polyvinyl alcohol (PVA)/2-hydroxypropyltrimethyl ammonium chloride chitosan (HACC) double-network (PVA/HACC-TA) hydrogels are prepared by a combination approach of cyclic freeze-thaw and soaking method. The prepared PVA/HACC-TA hydrogels are formed by hydrogen bond cross-linking and do not use any toxic and harmful cross-linking agents. Meanwhile, the prepared PVA/HACC-TA hydrogels have excellent mechanical properties, the maximum tensile strength can reach 4.13 MPa and the maximum tensile strain can attain 830%. In addition, PVA/HACC-TA hydrogels display good adhesion to different materials. At the same time, the PVA/HACC-TA hydrogels also show favorable antibacterial activities. Therefore, the excellent mechanical, adhesive, antibacterial and cytocompatible biomass hydrogels showed promising potential applications in the biomedicine field, especially as the skin wound dressings.

Rhodojaponin III-Loaded Chitosan Derivatives-Modified Solid Lipid Nanoparticles for Multimodal Antinociceptive Effects in vivo.

BackgroundRhodojaponin III (RJ-III) is a bioactive diterpenoid, which is mainly found in Rhododendron molle G. Don (Ericaceae), a potent analgesia in traditional Chinese medicine with several years of clinical applications in the country. However, its clinical use is limited by its acute toxicity and poor pharmacokinetic profiles. To reduce such limitations, the current study incorporated RJ-III into the colloidal drug delivery system of hydroxypropyl trimethyl ammonium chloride chitosan (HACC)-modified solid lipid nanoparticles (SLNs) to improve its sustained release and antinociceptive effects in vivo for oral delivery.ResultsThe optimized RJ-III@HACC-SLNs were close to spherical, approximately 134 nm in size, and with a positive zeta potential. In vitro experiments showed that RJ-III@HACC-SLNs were stable in the simulated gastric fluid and had a prolonged release in PBS (pH = 6.8). Pharmacokinetic results showed that after intragastric administration in mice, the relative bioavailability of RJ-III@HACC-SLNs was 87.9%. Further, it was evident that the peak time, half-time, and mean retention time of RJ-III@HACC-SLNs were improved than RJ-III after the administration. In addition, pharmacodynamic studies revealed that RJ-III@HACC-SLNs markedly reduced the acetic acid, hot, and formalin-induced nociceptive responses in mice (P < 0.001), and notably increased the analgesic time (P < 0.01). Moreover, RJ-III@HACC-SLNs not only showed good biocompatibility with Caco-2 cells in vitro but its LD50 value was also increased by 1.8-fold as compared with that of RJ-III in vivo.ConclusionThese results demonstrated that RJ-III@HACC-SLNs improved the pharmacokinetic characteristics of the RJ-III, thereby exhibiting toxicity-attenuating potential and antinociceptive enhancing properties. Consequently, HACC-SLNs loaded with RJ-III could become a promising oral formulation for pain management that deserves further investigation in the future.