Delivery System For Treatment Research Articles

Review of extended-release drug delivery systems for non-surgical treatment of inflammatory periodontal diseases

Relevance. The onset of periodontal pathogen resistance to systemic antibiotics revealed a new direction in periodontics. The characteristics of local drug delivery systems allow for a prolonged impact on periodontal pocket microbiota.Materials and methods. The non-interventional study was carried out by an analytical review of Russian and international scientific publications of independent clinical and laboratory research databases PubMed, ResearchGate, ScienceDirect, and eLIBRARY.RU for the last decade. The search was performed using the keywords: "periochip", "periodontal treatment", "the matrix", "tissue engineering", and "bioactive cryogels". The review included randomized controlled studies, controlled clinical trials, prospective and retrospective comparative cohort studies of drug delivery systems and systematic reviews.Results. In contrast to systemic drug administration, biodegradable local drug delivery systems provide long-lasting and effective treatment at the lesion site at much lower doses and in a shorter period of time. The prolonged drug activity time combined with non-surgical treatment of inflammatory periodontal diseases results in faster soft tissue regeneration. Gels, foams, fibres, bioactive cryogels, micro- and nanoparticles, and chips may be biodegradable matrices for the extended-release drug delivery system. The basic polymer for all these forms can be of natural origin (proteins, collagen), semi-synthetic (cellulose derivatives) or synthetic.Conclusion. Films, chips and bioactive cryogel are nowadays more common forms. Due to its unique structure, the bioactive drug cryogel can serve as a controlled and multifunctional system for drug delivery to the periodontal tissues, which determines its importance in periodontics and high interest f or further research.

Spiritualization of the Causes of Illness

Abstract This study focused on the spiritualization of the causes and treatment of illness within the African Prophetic churches in Zimbabwe (and its diaspora) in the context of the Covid-19 pandemic. The study comes at a time when most prophetic churches seem to maintain a position that sicknesses and diseases are caused by evil spirits. While mainline/missionary churches are of the opinion that most sicknesses and diseases were caused by bacteria, viruses, fungi, and parasites, hence advocating for scientific health delivery systems for treatment, most Zimbabwean prophetic churches are identifying spiritual causes of sickness and advocating for spiritual methods of healing and deliverance. These African prophetic churches seem to have remained steadfast in maintaining their African traditional worldview on the causes and treatment of diseases that predates the advent of Christianity in Africa. Accordingly, this study selected the white garment churches (Vapositori) and their responses to Covid-19 to underscore the argument that spiritualisation of the causes of illness among most African prophetic churches has remained intact. Methodologically, a descriptive phenomenological approach was used for data collection, while an interpretive phenomenological analysis (IPA) was used to interpret data collected. Three main video clips on the church’s theology on the origin of Covid-19 posted on social media by white garment church members were transliterated. Interviews with the white garment church members were also carried out to triangulate data relating to these video clips posted on social media. Using this methodology, the major finding was that white garment churches operate within the African religio-cultural milieu where illness/disease has the cause-effect dichotomy. Unless the cause is diagnosed, holistic healing cannot be realised.

Therapeutic Potential of Controlled Delivery Systems in Asthma: Preclinical Development of Flavonoid-Based Treatments.

Asthma is a chronic disease with increasing prevalence and incidence, manifested by allergic inflammatory reactions, and is life-threatening for patients with severe disease. Repetitive challenges with the allergens and limitation of treatment efficacy greatly dampens successful management of asthma. The adverse events related to several drugs currently used, such as corticosteroids and β-agonists, and the low rigorous adherence to preconized protocols likely compromises a more assertive therapy. Flavonoids represent a class of natural compounds with extraordinary antioxidant and anti-inflammatory properties, with their potential benefits already demonstrated for several diseases, including asthma. Advanced technology has been used in the pharmaceutical field to improve the efficacy and safety of drugs. Notably, there is also an increasing interest for the application of these techniques using natural products as active molecules. Flavones, flavonols, flavanones, and chalcones are examples of flavonoid compounds that were tested in controlled delivery systems for asthma treatment, and which achieved better treatment results in comparison to their free forms. This review aims to provide a comprehensive understanding of the development of novel controlled delivery systems to enhance the therapeutic potential of flavonoids as active molecules for asthma treatment.

Development of an Oral Isoliquiritigenin Self-Nano-Emulsifying Drug Delivery System (ILQ-SNEDDS) for Effective Treatment of Eosinophilic Esophagitis Induced by Food Allergy.

Isoliquiritigenin (ILQ) is a natural flavonoid with various pharmacological activities. In this study, we optimized the preparation method of self-nano-emulsion-loaded ILQ to further improve its bioavailability based on our previous study. In addition, its effect on the treatment of eosinophilic esophagitis was also evaluated. Combined surfactants and co-surfactants were screened, and the optimal formulation of ILQ-SNEDDS was determined according to droplet size, droplet dispersity index (DDI), and drug loading. The formulation was composed of ethyl oleate (oil phase), Tween 80 & Cremophor EL (surfactant, 7:3), and PEG 400 & 1,2-propylene glycol (cosurfactant, 1:1), with a mass ratio of 3:6:1. Its physicochemical properties, including drug loading, droplets' size, Zeta potential, appearance, and Fourier transform infrared (FTIR) spectroscopy, were characterized. In vitro release profile, in situ intestinal absorption, and in vivo pharmacokinetics were applied to confirm the improvement of oral ILQ bioavailability by NEDDS. Finally, the efficacy of ILQ-SNEDDS in the treatment of food allergy-induced eosinophilic esophagitis (EOE) was further evaluated. When the ILQ drug loading was 77.9 mg/g, ILQ-SNEDDS could self-assemble into sub-spherical uniform droplets with an average size of about 33.4 ± 2.46 nm (PDI about 0.10 ± 0.05) and a Zeta potential of approximately -10.05 ± 3.23 mV. In situ intestinal absorption showed that optimized SNEDDS significantly increased the apparent permeability coefficient of ILQ by 1.69 times, and the pharmacokinetic parameters also confirmed that SNEDDS sharply increased the max plasma concentration and bioavailability of ILQ by 3.47 and 2.02 times, respectively. ILQ-SNEDDS also significantly improved the apparent signs, allergic index, hypothermia and body weight of EoE model mice. ILQ-SNEDDS treatment significantly reduced the levels of inflammatory cytokines, such as TNF-α, IL-4, and IL-5, and the level of PPE-s-IgE in serum, and significantly inhibited the expression of TGF-β1 in esophageal tissue. SNEDDS significantly improved the solubility and bioavailability of ILQ. Additionally, ILQ-SNEDDS treatment attenuated symptomatology of EoE model mice, which was associated with inhibiting the production of TH2 inflammatory cytokines and PPE-s-IgE and the expression of TGF-β1. The above results shows that ILQ-SNEDDS has great potential as a good candidate for the treatment of eosinophilic esophagitis.

Propranolol-loaded nanostructured lipid carriers for topical treatment of infantile hemangioma

Oral administration of propranolol hydrochloride (PPL) is a first-line treatment option for infantile hemangioma. However, systemic drug distribution has been associated with severe adverse effects. Thus, this study aimed to investigate the feasibility of using PPL-loaded nanostructured lipid carriers (NLC) for topical drug delivery as a safer alternative for hemangioma treatment. Rosa rubiginosa essential oil was selected as a liquid lipid and possible therapeutic adjuvant. NLC with two different diameters (500 and 900 nm) were prepared and evaluated regarding stability, drug release, skin permeation, and cell activity. The NLC exhibited diameters within the confidence interval of the predictive model (569 ± 87 nm and 824 ± 58 nm), polydispersity index of 0.5, zeta potential close to neutrality, pH 5.5, and entrapment efficiency of 99%. The NLC were stable under refrigeration and controlled PPL release for 12 h, following first-order and Weibull kinetics (coefficient of determination >0.95). In the permeation assays with intact skin, the NLC exhibited a lower drug accumulation in the deeper skin layers, at least 5-fold less than the drug solution, with 19.5 and 12.7 μg cm−2 for the NLC of 500 nm and 900 nm, respectively, versus 88.1 μg cm−2 for the PPL solution. Moreover, no PPL was found from the NLC in the receptor medium the PPL solution resulted in skin permeation of up to 43.4 ± 5.9 μg cm−2. Furthermore, this trend was maintained even when the formulations were applied to a skin model in which hair follicles were blocked. Lastly, PPL-loaded NLC exhibited significant toxic, anti-proliferative, and anti-migratory effects over human brain microvascular endothelial cells superior to the non-formulated drug. In fact, PPL-loaded NLC inhibited cell proliferation by ≥ 50% after 6 days and limited cell migration to approximately 25%, compared to approximately 100% of controls. Thus, topical PPL-loaded NLC proved to be a promising drug delivery system for the topical treatment of infantile hemangioma.

Phytotherapeutic Potential of Natural Herbal Medicines for Management of Psoriasis: Current Status

Pharmacognosy Research,2023,15,1,42-55.DOI:10.5530/097484900261Published:December 2022Type:Review ReportAuthors:Nupur Maheshwari, Neelesh Maheshwari, Dinesh Kumar Mishra, and Anju Goyal Author(s) affiliations:Nupur Maheshwari1, Neelesh Maheshwari2,*, Dinesh Kumar Mishra3, Anju Goyal1 1B.N. Institute of Pharmaceutical Sciences, B.N. University, Udaipur, Rajasthan, INDIA. 2School of Pharmacy, Sangam University, Bhilwara, Rajasthan, INDIA. 3Indore Institute of Pharmacy, Indore, Madhya Pradesh, INDIA. Abstract:Psoriasis is a complex multifunctional inflammatory autoimmune skin disease, which is mainly characterized by activation of T-cell (T-lymphocyte), abnormal proliferation keratinocyte, local vascular changes and activation of the neutrophil. A number of therapies are being used to treat psoriasis including topical, systemic and phototherapy recpectively but none of them is able to cure the disease completely, precluding the long-term serious side effects for the human body. In contrast to these, herbal therapies can play an important role for treatment of psoriasis. With this endeavor, this review reports the recent developments and patent showing potential of herbal therapy for treatment of psoriasis along with future prospect in the field of traditional and novel drug delivery system (NDDS) for treatment of psoriasis. Keywords:Herbal drug, Hyperproliferation, Keratinocyte, Novel drug delivery systems, PsoriasisView:PDF (423.12 KB)

Recent Advances in Nanodrug Delivery System for Tumor Combination Treatment Based on Photothermal Therapy

AbstractAlthough photothermal therapy (PTT) can act on tumors alone, resulting in tumor shrinkage or even eradication, this effect is short‐lived, and the tumor may regrow. Thus, the most helpful contribution of PTT to cancer therapy is to employ it in conjunction with other tumor therapies, such as chemotherapy, immunotherapy, photodynamic therapy, gene therapy, radiotherapy therapy, and multiple combination therapy to boost treatment efficacy. This paper covers the benefits and drawbacks of combining photothermal therapy with various therapeutic approaches by the nanodrug delivery system and the possibilities and obstacles of clinical combination therapy.

Development and evaluation of Simvastatin based SNEDDS for treatment of Alzheimer’s disease

AbstractBackgroundThe purpose of this research work to improve solubility and bioavailability of Simvastatin using self nano‐emulsifying drug delivery system (SNEDDS) for treatment the Alzheimer’s disease.MethodSelf emulsifying property of various oils including essential oils was evaluated with suitable surfactants and co‐surfactants. Validation of method for accuracy, repeatability, Interday and intraday precision, ruggedness, and robustness were within the acceptable limits. The liquid SNEDDS was prepared and optimized using ternary phase diagram, thermodynamic, centrifugation and cloud point studies.ResultThe globule size of optimized formulations was less than 200 nm which could be acceptable nanoemulsion size range. The mean droplet size, drug loading, PDI and zeta potential were found to be 141.0 nm, 92.22%, 0.23 and ‐10.13 mV and 153.5nm, 93.89%,0.41 and ‐11.7 mV and 164.26 nm, 95.26%, 0.41 and ‐10.66mV respectively. The best formulations were subjected to FESEM for surface morphology.ConclusionFormulation development, and evaluation of simvastatin loaded self nano‐emulsifying drug delivery system (SNEDDS) for treatment the Alzheimer’s disease were carried out.

Stimuli-responsive and biomimetic delivery systems for sepsis and related complications.

Sepsis, a consequence of an imbalanced immune response to infection, is currently one of the leading causes of death globally. Despite advances in the discoveries of potential targets and nanotechnology, sepsis still lacks effective drug delivery systems for optimal treatment. Stimuli-responsive and biomimetic nano delivery systems, specifically, are emerging as advanced bio-inspired nanocarriers for enhancing the treatment of sepsis. Herein, we present a critical review of different stimuli-responsive systems, including pH-; enzyme-; ROS- and toxin-responsive nanocarriers, reported in the delivery of therapeutics for sepsis. Biomimetic nanocarriers, utilizing natural pathways in the inflammatory cascade to optimize sepsis therapy, are also reviewed, in addition to smart, multifunctional vehicles. The review highlights the nanomaterials designed for constructing these systems; their physicochemical properties; the mechanisms of drug release; and their potential for enhancing the therapeutic efficacy of their cargo. Current challenges are identified and future avenues for research into the optimization of bio-inspired nano delivery systems for sepsis are also proposed. This review confirms the potential of stimuli-responsive and biomimetic nanocarriers for enhanced therapy against sepsis and related complications.

Micelles in Cancer Therapy: An Update on Preclinical and Clinical Status.

In the recent years, Micelles represent a promising carrier for the treatment and diagnosis of cancer. Architecturally, micelles are self-assembled nanosized colloidal aggregates prepared from amphiphilic surfactant with a hydrophobic core and hydrophilic shell. Such a composition makes them a potential carrier for delivery of hydrophobic anticancer drugs with in their core. Micelles have received increasing interest as an enhanced permeability and retention (EPR) targeted drug delivery systems for cancer treatment. Micelles can be modified to contribute various attractive properties, for instance, active targeting, stimuli-responsiveness. They have also proven their ability in drug targeting to tumor tissue, enhanced drug accumulation, drug stabilization, tissue penetration, prolong circulation, in vivo biocompatibility, biodegradability and reduced side effects. Micelles have displayed a vital role in multidrug delivery for cancer therapy. The aim of the present review is to provide an overview on the status of micellar nanoformulations for anticancer agents, including their pre-clinical and clinical researches. Emphasis is placed on presenting the newer strategies to enhance the therapeutic efficacy of anticancer drug at the target site. The type of co-polymers used and methods for the preparation of micelles are also highlighted in the paper.

Inhaled platelet vesicle-decoyed biomimetic nanoparticles attenuate inflammatory lung injury.

Acute lung injury (ALI) is an inflammatory response which causes serious damages to alveolar epithelia and vasculature, and it still remains high lethality and mortality with no effective treatment. Based on the inflammatory homing of platelets and cell membrane cloaking nanotechnology, in this study we developed a biomimetic anti-inflammation nanoparticle delivery system for ALI treatment. PM@Cur-RV NPs were designed by combining the poly (lactic-co-glycolic acid) nanoparticles (NPs) coated with platelet membrane vesicles (PM) for the purpose of highly targeting delivery of curcumin (Cur) and resveratrol (RV) to inflammatory lungs. PM@Cur-RV NPs showed good biocompatibility and biosafety both in vitro and in vivo. Accumulation of NPs into lung tract was observed after inhaled NPs. Remarkably, the inhalation of PM@Cur-RV NPs effectively inhibited lung vascular injury evidenced by the decreased lung vascular permeability, and the reduced proinflammatory cytokine burden in an ALI mouse model. The analysis of infiltrated macrophages in the lungs showed that the Cur-RV-modulated macrophage polarized towards M2 phenotype and the decreased histone lactylation might contribute to their anti-inflammation effects. Together, this work highlights the potential of inhalation of biomimetic nanoparticle delivery of curcumin and resveratrol for the treatment of pulmonary diseases.

A dual-targeting near-infrared biomimetic drug delivery system for HBV treatment.

Hepatitis B virus (HBV) infection is a serious global public health threat. It remains elusive to achieve a functional HBV cure with currently available antivirals. Herein, a photo-responsive delivery vehicle composed of Nd3+ -sensitized core-shell upconversion nanoparticle (UCNP), mesoporous silica nanoparticle (MSN), antisense oligonucleotides (ASOs), and capsid-binding inhibitor C39 was established, which was named UMAC according to the initials of its components. Subsequently, the as-synthesized delivery vehicle was encapsulated by β- D-galactopyranoside (Gal) modified red blood cell (RBC) membrane vesicles, which enabled precise targeting of the liver cells (UMAC-M-Gal). Both in vitro and in vivo experiments demonstrated that this biomimetic system could successfully achieve controlled drug release under light conditions at 808 nm, leading to effective suppression of HBV replication in this dual-targeted therapeutic approach. Together, these results substantiate the system has huge prospects for application to achieve functional HBV cure, and provides a promising novel strategy for drug delivery.

Photothermally Responsive Magnetic Nanoparticles for Nitric Oxide Release to Combat Staphylococcus aureus Biofilms

Nitric oxide (NO) is an emerging and promising antimicrobial agent for treating biofilms, yet its enrichment in biofilms has become a major challenge. In this contribution, iron oxide-polydopamine (Fe3O4-PDA) core–shell nanoparticles were fabricated and then loaded with (N,N′-di-sec-butyl-N,N′-dinitroso-1,4-phenylenediamine, BNN6), a NO donor, to yield a magnetic field-driven and near-infrared (NIR)-responsive NO delivery system for biofilm treatment. In a magnetic field, the nanoparticles were found to penetrate into and accumulate in the biofilms more effectively, resulting in a higher concentration of the nanoparticles in the biofilms, which upon exposure to NIR laser (808 nm) irradiation, heat up the local environment by the photothermal effect to trigger the release of more NO in a controlled manner. The combination of photothermal and NO gas therapies exhibited a synergistic antibacterial effect against Staphylococcus aureus biofilms in vitro, and the nanoparticles showed excellent antibacterial properties in vivo in the treatment of the mice wound infection model and accelerated the wound healing process. Overall, the Fe3O4-PDA–BNN6 nanoparticles realized spatial- and temporal-controlled release of NO in biofilms using NIR under a magnetic field, providing an effective antibiofilm strategy and taking the NO gas therapy one step closer to clinical application.

Self-assembly of DNA nanostructure containing cell-specific aptamer as a precise drug delivery system for cancer therapy in non-small cell lung cancer

BackgroundAs the most common subtype in lung cancer, the precise and efficient treatment for non-small cell lung cancer (NSCLC) remains an outstanding challenge owing to early metastasis and poor prognosis. Chemotherapy, the most commonly used treatment modality, is a difficult choice for many cancer patients due to insufficient drug accumulation in tumor sites and severe systemic side-effects. In this study, we constructed a cell-specific aptamer-modified DNA nanostructure (Apt-NS) as a targeting drug delivery system achieving the precision therapy for lung cancer.MethodsThe synthesis of DNA nanostructure and its stability were evaluated using gel electrophoresis. The targeting properties and internalization mechanism were investigated via flow cytometry and confocal analyses. Drug loading, release, and targeted drug delivery were determined by fluorescence detection, Zeta potentials assay, and confocal imaging. CCK8 assays, colony formation, cell apoptosis, metastasis analyses and in vivo experiments were conducted to assess the biological functions of DNA nanostructure.ResultsSelf-assembled DNA nanoparticles (Apt-NS) had excellent stability to serum and DNase I and the ability to specifically recognize A549 cells. Upon specific binding, the drug-loaded nanoparticles (Apt-NS-DOX) were internalized into target cells by clathrin-mediated endocytosis. Subsequently, DOX could be released from Apt-NS-DOX based on the degradation of the lysosome. Apt-NS-DOX exerted significant suppression of cell proliferation, invasion and migration, and also enhanced cell apoptosis due to the excellent performance of drug delivery and intracellular release, while maintaining a superior biosafety. In addition, the antitumor effects of Apt-NS-DOX were further confirmed using in vivo models.ConclusionsOur study provided cell-specific aptamer-modified DNA nanostructures as a drug-delivery system targeting A549 cells, which could precisely and efficiently transport chemotherapeutic drug into tumor cells, exerting enhanced antineoplastic efficacy. These findings highlight that DNA nanostructure serving as an ideal drug delivery system in cancer treatment appears great promise in biomedical applications.

Facile synthesis of curcumin-containing poly(amidoamine) dendrimers as pH-responsive delivery system for osteoporosis treatment

Osteoporosis is an age-related metabolic disease of bone, resulting in bone pain and even bone fragility and brittle fracture. Inhibiting overactive osteoclasts while promoting osteoblast activity is an ideal way to treat osteoporosis. Previous studies have demonstrated that natural compounds, such as curcumin (Cur) have dual roles both in promoting bone formation and inhibiting bone resorption, making them promising candidates for osteoporosis treatment. However, their poor water solubility, high dosage of curative effect and significant toxicity to other organs have largely limited their clinical translations. In this study, a novel method was reported to conjugate Cur and poly(amidoamine) dendrimers (PAD) using hexachlorocyclotriphosphazene (HCCP) as the linkage through a one-pot reaction, forming stable and uniform Cur loaded nanospheres (HCCP-Cur-PAD, HCP NPs). Owing to the hydrophilicity of PAD and hydrophobicity of Cur, HCP NPs can self-assemble into nanoparticles with particle size of 138.8 ± 78.7 nm and display excellent water dispersity. The loading capacity of Cur can reach 27.2% and it can be released from HCP NPs with pH-responsiveness. In vitro experimental results demonstrated that the HCP NPs entered lysosomes by endocytosis and proved dual anti-osteoporosis effects of inhibiting osteoclasts and promoting osteoblasts.

Preparation of 6-Mercaptopurine Loaded Liposomal Formulation for Enhanced Cytotoxic Response in Cancer Cells.

6-Mercaptopurine (6-MP) is a well-known immunosuppressive medication with proven anti-proliferative activities. 6-MP possesses incomplete and highly variable oral absorption due to its poor water solubility, which might reduce its anti-cancer properties. To overcome these negative effects, we developed neutral and positively charged drug-loaded liposomal formulations utilizing the thin-film hydration technique. The prepared liposomal formulations were characterized for their size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The average size of the prepared liposomes was between 574.67 ± 37.29 and 660.47 ± 44.32 nm. Positively charged liposomes (F1 and F3) exhibited a lower PDI than the corresponding neutrally charged ones (F2 and F4). Entrapment efficiency was higher in the neutral liposomes when compared to the charged formulation. F1 showed the lowest IC50 against HepG2, HCT116, and MCF-7 cancer cells. HepG2 cells treated with F1 showed the highest level of inhibition of cell proliferation with no evidence of apoptosis. Cell cycle analysis showed an increase in the G1/G0 and S phases, along with a decrease in the G2/M phases in the cell lines treated with drug loaded positively charged liposomes when compared to free positive liposomes, indicating arrest of cells in the S phase due to the stoppage of priming and DNA synthesis outside the mitotic phase. As a result, liposomes could be considered as an effective drug delivery system for treatment of a variety of cancers; they provide a chance that a nanoformulation of 6-MP will boost the cytotoxicity of the drug in a small pharmacological dose which provides a dosage advantage.

Atractylodes lancea for cholangiocarcinoma: Modulatory effects on CYP1A2 and CYP3A1 and pharmacokinetics in rats and biodistribution in mice.

Atractylodes lancea (Thunb.) DC. (A. lancea: AL) is a promising candidate for the treatment of cholangiocarcinoma (bile duct cancer). The study investigated (i) the propensity of capsule formulation of the standardized extract of AL (formulated AL) to modulate mRNA and protein expression and activities of CYP1A2 and CYP3A1 in rats after long- and short-term exposure, (ii) the pharmacokinetics of atractylodin (ATD: active constituent) after long-term administration of formulated AL, and (iii) the biodistribution of atractylodin-loaded polylactic-co-glycolic acid (ATD-PLGA-NPs) in mice. To investigate CYP1A2 and CYP3A1 modulatory activities following long-term exposure, rats of both genders received oral doses of the formulated AL at 1,000 (low dose), 3,000 (medium dose), and 5,000 (high dose) mg/kg body weight daily for 12 months. For short-term effects, male rats were orally administered the formulated AL at the dose of 5,000 mg/kg body weight daily for 1, 7, 14 and 21 days. The pharmacokinetic study was conducted in male rats after administration of the formulated AL at the dose of 5,000 mg/kg body weight daily for 9 months. The biodistribution study was conducted in a male mouse receiving ATD-PLGA-NPs at the equivalent dose to ATD of 100 mg/kg body weight. The high dose of formulated AL produced an inducing effect on CYP1A2 but an inhibitory effect on CYP3A1 activities in male rats. The low dose, however, did not inhibit or induce the activities of both enzymes in male and female rats. ATD reached maximum plasma concentration (Cmax) of 359.73 ng/mL at 3 h (tmax). Mean residence time (MRT) and terminal phase elimination half-life (t1/2z) were 3.03 and 0.56 h, respectively. The extent of biodistribution of ATD in mouse livers receiving ATD-PLGA-NPs was 5-fold of that receiving free ATD. Clinical use of low-dose AL should be considered to avoid potential herb-drug interactions after long-term use. ATD-PLGA-NPs is a potential drug delivery system for cholangiocarcinoma treatment.

H2O2/NIR-sensitive “two-step” nano theranostic system based hollow mesoporous copper sulfide/hyaluronic acid/JWH133 as an optimally designed delivery system for multidimensional treatment of RA

Cannabinoid receptors are widely distributed in many cells in Rheumatoid arthritis RA and strengthening factor to boost the development of RA diseases. Here, the hollow mesoporous copper sulfide (CuS) was used as the carrier skeleton and the cannabinoid type 2 (CB2) receptor agonist JWH133 was efficiently loaded inside of CuS through adsorption, then the outer layer was modified with hyaluronic acid (HA) to prevent the leakage of internal drugs. After the CuS-JWH133@HA nano carrier reached the target area, HA responsive cracked under RA microenvironment to realize the first step of accurate drug delivery of JWH133, and the thermally responsive CuS under near-infrared (NIR) promoted the release of internal drugs. Then, JWH133 specifically combined CB2 receptors on the surface of macrophage, synovial cells and osteoblasts to realize the second step of drug delivery. The inflammatory factors secreted by cells are significantly inhibited, and the activity of osteoblasts was significantly enhanced. Therapeutic effect by CuS-JWH133@HA of RA was well verified by decreasing levels of inflammation in vivo and improvement of inflamed and swollen joints of mice. The CuS-JWH133@HA nanocomposite showed satisfactory multidimensional therapeutic effect of RA in vitro and in vivo, which provided a novel idea for RA treatment.

Preparation and characterization of benzydamine hydrochloride-loaded lyophilized mucoadhesive wafers for the treatment of oral mucositis

Chemo/radiotherapy-induced oral mucositis (OM) has painful ulcers that can impair patients' lives. This study aimed to develop and characterize (in vitro and in vivo) benzydamine (BNZ) freeze-dried mucoadhesive wafers from chitosan (CS) in combination with different hydrophilic polymers as a locally controlled delivery system for OM treatment. The porous (69–83%) optimum wafers (0.02–0.03 g and 3.2–4.3 mm) released 90–95% of their drug content over 8 h and demonstrated 40–53 g mucoadhesion strength. Mechanical evaluations of F1 (CS) and F14 (CS/HPMC (3:1)) selected formulations showed modulus of elasticity, tensile strength, and % elongation at break ranging from 0.2 to 0.3 MPa, 0.01–0.02 MPa, and 15–18%, respectively. The antimicrobial efficacy of BNZ-loaded wafers was significantly higher than drug-free ones. The extract solutions of the drug-free and BNZ-loaded wafers revealed 100 and 20% viability in human gingival fibroblasts (HGFs) exposure. In vivo analysis demonstrated that BNZ-loaded wafers represented a significant reduction in macroscopic evaluation of OM and histopathological tests compared to positive and negative controls and drug-free wafers. Conclusively, lyophilized F1 and F14 mucoadhesive wafers had acceptable structural, mechanical, and biological properties and might be promising drug delivery systems for OM.

Drug delivery systems for treatment of temporomandibular joint osteoarthritis.

The number of people suffering from temporomandibular joint osteoarthritis (TMJOA) has been increasing. TMJOA cause joint noise, pain on TMJ and/or masticatory muscles, and restricted mandibular movement, which disturb eating, laughing and conversation, and impose serious lifestyle impediments. Chondrocyte apoptosis, extracellular matrix degradation, synovitis, and subchondral bone remodeling are the main pathological features of TMJOA. Various drug delivery systems are developed to controlled release at specific activation sites with high bioactivity and inhibit rapid dilution to enable long-term therapeutic response, which present great potential for the treatment of TMJOA. This review focuses on recently developed drug delivery systems by different administration in the TMJOA treatment, and summarizes their effects, duration, safety, and limitations, which would pave the way for development of TMJOA therapy.