Current Drug Delivery - Volume 21, Issue 8, 2024

Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, pose significant challenges for effective treatment due to the complex nature of the central nervous system and the limited delivery of therapeutic agents to the brain. Biomaterial-based drug delivery systems offer promising strategies to overcome these challenges and improve therapeutic outcomes. These systems utilize various biomaterials, such as nanoparticles, hydrogels, and implants, to deliver drugs, genes, or cells to the affected regions of the brain. They provide advantages such as targeted delivery, controlled release, and protection of therapeutic agents. This review examines the role of biomaterials in drug delivery for neurodegeneration, discussing different biomaterialbased approaches, including surface modification, encapsulation, and functionalization techniques. Furthermore, it explores the challenges, future perspectives, and potential impact of biomaterialbased drug delivery systems in the field of neurodegenerative diseases.

Immunomodulatory mechanisms are indispensable and key factors in maintaining the balance of the environment in humans. When the immune function of the immune system is impaired, autoimmune diseases occur. Excessive body fatigue, natural aging of the human body, malnutrition, genetic factors and other reasons cause low immune function, due to which the body is prone to being infected by bacteria or cancer. Clinically, the existing therapeutic drugs still have problems such as high toxicity, long treatment cycle, drug resistance and high price, so we still need to explore and develop a high efficiency and low toxicity drug. Poly(lactic-co-glycolic acid) (PLGA) refers to a nontoxic polymer compound that exhibits excellent biocompatibility. Traditional Chinese medicine (TCM) monomers come from natural plants, and have the characteristics of high efficiency and low toxicity. Applying PLGA to TCM monomers can make up for the defects of traditional dosage forms, improve bioavailability, reduce the frequency and dosage of drug use, and reduce toxicity and side effects, thus having the characteristics of sustained release and targeting. Accordingly, PLGA nanoparticles loaded with TCM monomers have been the focus of development. The previous research on drug loading advantages, preparation methods, and immune regulation of TCM PLGA nanoparticles is summarized in the following sections.

Deformable lipidic-nano carriers are a category of advanced liposomal formulations. Deformable lipidic-nano carriers have a specific character to transform by rearranging the lipidic backbone to squeeze themself through a pore opening ten times smaller than their diameter when exposed to a variable condition like hydration gradient as these have potentially been used as a non-invasive delivery system to transdermally migrate various therapeutic agents for over three decades. Despite their vast application in transdermal drug delivery system, non-uniformity to express their chemical nature still exist and authors use various terms synonymously and interchangeably with each other. The present study delineates the terminologies used to express different derived deformable vesicular carriers to harmonize the terminological use. It also includes the effectiveness of deformable nanocarriers like Transferosomes, Ethosomes, Menthosomes, Invasomes, and Glycerosomes in skin conditions like basal cell carcinoma, fungal and viral infections, and hyperpigmentation disorders, along with others. Various review and research articles were selected from the ‘Pubmed’ database. The keywords like Transferosomes, Flexi-vesicular system, ultra-deformable vesicles, and nano-vesicular systems were used to extract the data. The data was reviewed and compiled to categorically classify different flexible vesicular systems. The composition of the different vesicular systems is identified and a report of various pathological conditions where the use of flexible lipid nanocarrier systems was implemented is compiled. The review also offers suggestive approaches where the applicability of these systems can be explored further.

Magnetotactic bacteria (MTBs) and their organelles, magnetosomes, are intriguing options that might fulfill the criteria of using bacterial magnetosomes (BMs). The ferromagnetic crystals contained in BMs can condition the magnetotaxis of MTBs, which is common in water storage facilities. This review provides an overview of the feasibility of using MTBs and BMs as nanocarriers in cancer treatment. More evidence suggests that MTBs and BMs can be used as natural nanocarriers for conventional anticancer medicines, antibodies, vaccine DNA, and siRNA. In addition to improving the stability of chemotherapeutics, their usage as transporters opens the possibilities for the targeted delivery of single ligands or combinations of ligands to malignant tumors. Magnetosome magnetite crystals are different from chemically made magnetite nanoparticles (NPs) because they are strong single-magnetic domains that stay magnetized even at room temperature. They also have a narrow size range and a uniform crystal morphology. These chemical and physical properties are essential for their usage in biotechnology and nanomedicine. Bioremediation, cell separation, DNA or antigen regeneration, therapeutic agents, enzyme immobilization, magnetic hyperthermia, and contrast enhancement of magnetic resonance are just a few examples of the many uses for magnetite-producing MTB, magnetite magnetosomes, and magnetosome magnetite crystals. From 2004 to 2022, data mining of the Scopus and Web of Science databases showed that most research using magnetite from MTB was carried out for biological reasons, such as in magnetic hyperthermia and drug delivery.

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that initially affects small joints and then spreads to the bigger joints. It also affects other organs of the body such as lungs, eyes, kidneys, heart, and skin. In RA, there is destruction of cartilage and joints, and ligaments and tendons become brittle. Damage to the joints leads to abnormalities and bone degradation, which may be quite painful for the patient. Method: The nano-carriers such as liposomes, phytosomes, nanoparticles, microcapsules, and niosomes are developed to deliver the encapsulated phytoconstituents to targeted sites for the better management of RA. Results: The phytoconstituents loaded nano-carriers have been used in order to increase bioavailability, stability and reduce the dose of an active compound. In one study, the curcumin-loaded phytosomes increase the bioavailability of curcumin and also provides relief from RA symptoms. The drug-loaded nano-carriers are the better option for the management of RA. Conclusion: In conclusion, there are many anti-arthritic herbal and synthetic medicine available in the market that are currently used in the treatment of RA. However, chronic use of these medications may result in a variety of side effects. Because therapy for RA is frequently necessary for the rest of ones life. The use of natural products may be a better option for RA management. These phytoconstituents, however, have several disadvantages, including limited bioavailability, low stability, and the need for a greater dosage. These problems can be rectified by using nano-technology.

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD), and the global incidence rate is 0.5 ~ 1%. Existing medications might reduce symptoms, however, there is no known cure for this illness. Etanercept (EN) can competitively inhibit TNF-α binding to the TNF receptor on the cell surface to treat RA. However, subcutaneous injection of free EN predisposes to systemic distribution and induces immune system hypofunction. Draining lymph nodes (LNs) play a significant role in the onset, maintenance, and progression of RA as they are the primary sites of aberrant immune response and inflammatory cytokine production. Aim: The purpose of this study was to successfully treat RA with etanercept by encapsulating it in nanoemulsions (NEs/EN) and then delivering it specifically to draining LNs. The EN-loaded NEs were prepared by high-pressure homogenization method and modified with DSPE-mPEG&2000& and Ca(OH)&2&. Methods: A novel nano-emulsion (NE) was constructed to deliver EN (NE/EN) to RA-draining LNs. To decrease aggregation and load EN, DSPE-mPEG&2000& and Ca(OH)&2& were successively decorated on the surface of the lipid injectable emulsions. The hydrodynamic diameter and morphology of NEs/EN were investigated by using a laser particle size analyzer and transmission electron microscopy, respectively. The in vivo fluorescence imaging system was used to study the in vivo LN targeting ability of the formulation. In the therapeutic experiment, NEs/EN was subcutaneously administrated to inhibit the development of the mouse arthritis model. Results: Circular dichroism spectrum and L929 cell experiment confirmed that NEs encapsulation had no impact on the biological activity of EN. In vivo investigation on collagen-induced arthritis (CIA) mouse model showed that NEs/EN have good inguinal lymph node targeting capabilities, as well as, anti-inflammatory effect against RA. Compared with the free group, the paw thickness and arthritic score in NEs/EN group were significantly alleviated. Moreover, the concentration of pro-inflammatory cytokines TNF-α and IL-1β in NEs/EN-treated mice was lower than that in free EN. Conclusion: NEs/EN effectively improve the effectiveness of EN in the treatment of RA. Our work provides an experimental foundation for expanding the clinical application of EN.

Background: Tumor-associated macrophages (TAMs) are crucial for non-small cell lung cancer (NSCLC) development. Objective: In this study, polylactic acid-co-glycolic acid (PLGA)-polyethylenimine (PEI) nanobubbles (NBs) carrying STAT6 siRNA were prepared and combined with ultrasound-mediated nanobubbles destruction (UMND) to silence the STAT6 gene, ultimately repolarizing TAMs from the M2 to the M1 phenotype, treating NSCLC in vitro. Methods: PLGA-PEI NBs-siRNA were prepared and characterised, and their respective ultrasound imaging, biological stabilities and cytotoxicities were detected. Transfection efficiency was evaluated by fluorescence microscopy and flow cytometry. Repolarization of THP-1-derived M2-like macrophages was determined by qPCR and flow cytometry. NSCLC cells (A549) were co-cultured with transfected M2-like macrophages or their associated conditioned medium (CM). Western blotting was used to detect STAT6 gene silencing in M2-like macrophages and markers of epithelial and mesenchymal in A549 cells. The proliferation of A549 cells was detected using CCK-8 and cell colony formation assays. Transwell assays were used to detect the migration and invasion of A549 cells. Results: PLGA-PEI NBs-siRNA had an average size of 223.13 ± 0.92 nm and a zeta potential of about -5.59 ± 0.97 mV. PLGA-PEI NBs showed excellent ultrasonic imaging capability in addition to biological stability to protect siRNA from degradation. UMND enhanced PLGA-PEI NBs-STAT6 siRNA transfection in M2-like macrophages, which made M2-like macrophages repolarize to M1-like macrophages and prevented proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in A549 cells. Conclusion: UMND enhanced PLGA-PEI NBs-STAT6 siRNA to repolarize TAMs from the M2 to the M1 phenotype, thus treating NSCLC. These findings provide a promising therapeutic approach for enhancing NSCLC immunotherapy.

Background: Among various materials designed for anticancer drug transport, sulfide nanoparticles are uniquely intriguing owing to their spectral characteristics. Exploration of newer nanoscale copper sulfide particles with dysprosium doping is reported herein. It leads to a change in the physicochemical properties of the sulfide nanoparticles and hence the difference in drug release and cytotoxicity. Objective: We intend to purport the suitably engineered cobalt sulfide and dysprosium-doped cobalt sulfide nanoparticles that are magnetic and NIR-absorbing, as drug delivery vehicles. The drug loading and release are based on the supramolecular drug complex formation on the surface of the nanoparticles. Method: The nanomaterials are synthesized employing hydrothermal procedures, coated with a biocompatible poly-β-cyclodextrin, and characterized using the methods of diffractometry, microscopy, spectroscopy, thermogravimetry and magnetometry. The sustained drug release is investigated in vitro. 5-Fluorouracil is loaded in the nanocarriers. The empty and 5-fluorouracil-loaded nanocarriers are screened for their anti-breast cancer activity in vitro on MCF-7 cells. Results: The size of the nanoparticles is below 10 nm. They show soft ferromagnetic characteristics. Further, they show broad NIR absorption bands extending up to 1200 nm, with the dysprosium-doped material displaying greater absorbance. The drug 5-fluorouracil is encapsulated in the nanocarriers and released sustainably, with the expulsion duration extending over 10 days. The IC&50& of the blank and the drug-loaded cobalt sulfide are 16.24 ± 3.6 and 12.2 ± 2.6 μg mL^-1, respectively. For the drug-loaded, dysprosium-doped nanocarrier, the IC&50& value is 9.7 ± 0.3 μg mL^-1. Conclusion: The ultrasmall nanoparticles possess a size suitable for drug delivery and are dispersed well in the aqueous medium. The release of the loaded 5-fluorouracil is slow and sustained. The anticancer activity of the drug-loaded nanocarrier shows an increase in efficacy, and the cytotoxicity is appreciable due to the controlled release. The nanocarriers show multi-functional characteristics, i.e., magnetic and NIR-absorbing, and are promising drug delivery agents.

Introduction: With the rapid development of nanotechnology, the research and development of nano-drugs have become one of the development directions of drug innovation. The encapsulation of the nanoparticles can change the biological distribution of the drug in vivo and improve the bioavailability of the drug in vivo. Naringenin is poorly soluble in water and has a low bioavailability, thus limiting its clinical application. The main purpose of this study was to develop a nano-sized preparation that could improve the oral bioavailability of naringenin. Methods: Chitosan oligosaccharide modified naringenin-loaded bovine serum albumin nanoparticles (BSA-COS@Nar NPs) were prepared by emulsification solvent evaporation and electrostatic interaction. The nanoparticles were characterized by HPLC, laser particle size analyzer, transmission electron microscope and X-ray diffraction analysis. The release in vitro was investigated, and the behavior of nanoparticles in rats was also studied. The caco-2 cell model was established in vitro to investigate the cytotoxicity and cellular uptake of nanoparticles. Results: BSA-COS@Nar NPs were successfully prepared, and the first-order release model was confirmed in vitro release. In vivo pharmacokinetic results indicated that the area under the drug concentration- time curve (AUC) of BSA-COS@Nar NPs was 2.37 times more than free naringenin. Cytotoxicity and cellular uptake results showed that BSA-COS@Nar NPs had no significant cytotoxic effect on Caco- 2 cells and promoted cellular uptake of the drug. Conclusion: BSA-COS@Nar NPs could improve the in vivo bioavailability of naringenin.

Background: Different oral appliances (OAs) have been proposed to control sleep bruxism (SB) detrimental effects on the stomatognathic system. Objective: The aim of the study was to evaluate the effect of different OAs on SB activity and masticatory muscle activity (sMMA) measured by EMG. Methods: This longitudinal cohort study was conducted on 51 patients (21 M, 30 F, mean age 26,5 ± 3,5) suffering from SB diagnosed with a validated portable EMG-ECG holter and wearing different OAs: occlusal splints, functional appliance with metallic bites and clear aligners followed after 1 week, 1 month, 3 months, 6 months and 12 months from delivery. A control group of 16 non-treated SB patients (6 M, 10 F mean age 27,1 ± 1,4) was used as a reference. A multiple regression analysis was performed to estimate the differences between groups. The level of significance was set as P value <0,05. Results: Occlusal splint reduced sleep bruxism index after 1 week, 3, 6 and 12 months from delivery while functional appliance only after 12 months. Occlusal splints reduced general phasic contractions only in the first week and sleep bruxism-related phasic contractions at 1 week, 3 and 6 months after delivery with no significant reductions after 12 months. Patients wearing clear aligners showed a reduction in general tonic contractions after 6 and 12 months. Conclusion: Resin and metal bites can reduce sleep bruxism index, while resin bites can reduce sleep bruxism-related phasic contractions. Clear aligners do not influence sleep bruxism index but can reduce tonic contractions.