Phytocompounds and lipid-based drug delivery system for neurodegenerative diseases

Across the annals of time,organic molecules sourced from nature have found innumerable uses within the realms of healthcare,pharmaceuticals,and the study of living organisms.This abundant source of natural compounds has exhibited immense promise in the cure of diverse ailments,mainly neurodegenerative diseases owing to their minimum toxic and adverse effects.However,different challenges exist with phytocompounds from plants such as poor permeation,poor solubility(water/lipid),unsteadiness under extremely acidic pH conditions,and lack of targeting specificity.Furthermore,as a result of the existence of blood-brain barrier membrane and inconvenient pharmacokinetics characteristics of phytocompounds,their passage into the brain is constrained.In order to address this issue and augment the transportation of medications into the brain at a therapeutically effective level,it is imperative to formulate an innovative and pragmatic strategy.Many papers have shown that nanoformulations containing phytocompounds(resveratrol,quercetin,ferulic acid,curcumin,berberine,etc.)effectively improved many neurodegenerative diseases such as Parkinson’s,Alzheimer’s and Huntington’s diseases.This study provides an overview of phytocompounds that are used in nanosized lipid drug delivery systems.These systems are categorized according to lipid types and preparation techniques used in the formulation.Some studies regarding these systems and phytocompounds are also summarized.

Recent advances in zwitterionic nanoscale drug delivery systems to overcome biological barriers

Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects.Although several nDDS have been successfully approved for clinical use up to now,biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment.Polyethylene glycol(PEG)-modification(or PEGylation)has been regarded as the gold standard for stabilising nDDS in complex biological environment.However,the accelerated blood clearance(ABC)of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications.Zwitterionic polymer,a novel family of antifouling materials,have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility.Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues.More impressively,zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution,pressure gradients,impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications.The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS,which could facilitate their better clinical translation.Herein,we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlyingmechanisms.Finally,prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.

The state-of-the-art of atmospheric pressure plasma for transdermal drug delivery

Plasma-enhanced transdermal drug delivery(TDD) presents advantages over traditional methods,including painless application, minimal skin damage, and rapid recovery of permeability. To harness its clinical potential, factors related to plasma’s unique properties, such as reactive species and electric fields, must be carefully considered.This review provides a concise summary of conventional TDD methods and subsequently offers a comprehensive examination of the current state-of-the-art in plasma-enhanced TDD. This includes an analysis of the impact of plasma on HaCaT human keratinocyte cells, ex vivo/in vivo studies, and clinical research on plasma-assisted TDD. Moreover, the review explores the effects of plasma on skin physical characteristics such as microhole formation, transepidermal water loss(TEWL), molecular structure of the stratum corneum(SC), and skin resistance. Additionally, it discusses the involvement of various reactive agents in plasma-enhanced TDD, encompassing electric fields,charged particles, UV/VUV radiation, heat, and reactive species. Lastly, the review briefly addresses the temporal behavior of the skin after plasma treatment, safety considerations, and potential risks associated with plasma-enhanced TDD.

Ionic liquids as the effective technology for enhancing transdermal drug delivery: Design principles, roles, mechanisms, and future challenges

Ionic liquids (ILs) have been proven to be an effective technology for enhancing drug transdermal absorption. However, due to the unique structural components of ILs, the design of efficient ILs and elucidation of action mechanisms remain to be explored. In this review, basic design principles of ideal ILs for transdermal drug delivery system (TDDS) are discussed considering melting point, skin permeability, and toxicity, which depend on the molar ratios, types, functional groups of ions and inter-ionic interactions. Secondly, the contributions of ILs to the development of TDDS through different roles are described: as novel skin penetration enhancers for enhancing transdermal absorption of drugs;as novel solvents for improving the solubility of drugs in carriers;as novel active pharmaceutical ingredients (API-ILs) for regulating skin permeability, solubility, release, and pharmacokinetic behaviors of drugs;and as novel polymers for the development of smart medical materials. Moreover, diverse action mechanisms, mainly including the interactions among ILs, drugs, polymers, and skin components, are summarized. Finally, future challenges related to ILs are discussed, including underlying quantitative structure-activity relationships, complex interaction forces between anions, drugs, polymers and skin microenvironment, long-term stability, and in vivo safety issues. In summary, this article will promote the development of TDDS based on ILs.

Advances in Transdermal Drug Delivery for Cancer Therapy

Transdermal drug delivery offers a promising alternative to traditional cancer therapies by providing a non-invasive,controlled,and targeted delivery of therapeutic agents.This paper explores the advancements,benefits,and challenges associated with transdermal drug delivery systems(TDDS)in cancer treatment.It highlights the mechanisms of action,key technologies,and the potential impact on patient outcomes.By examining recent studies and clinical trials,this paper aims to provide a comprehensive overview of the efficacy,safety,and prospects of transdermal drug delivery in oncology.

Characteristics and Transdermal Drug Delivery of Triamcinolone-Acetonide-Acetate-Loaded Solid Lipid Nanoparticles Carbomer Gel

Aim To prepare triamcinolone-acetonide-acetate (TAA)-loaded solid lipidnanoparticles (SLN) carbomer gel with tripalmitin glyceride (TPG), and investigate theircharacteristics and transdermal drug delivery. Methods SLN suspension was prepared by high-pressurehomogenization technique, and then mixed with carbomer gel matrix to get SLN gel. The morphology,particle size with polydispersi-ty index (PI) and zeta potential were examined by atomic forcemicroscopy (AFM) and photon correlation spectroscopy (PCS). The entrapment efficiency, stability andin vitro drug release were also studied. The transdermal drug delivery through porcine ear skin wasevaluated using modified Franz diffusion cells. Results The SLN had a spherical shape with theaverage size of (95.5 - 186.2) nm, the zeta potential of (-26.3- -15.7) mV and the entrapmentefficiency of 67.4%-90.3% for different TAA encapsulated compounds. TAA-SLN carbomer gel had goodstability, the release profile in vitro fitted Higuchi equation. In comparison with conventionalhydrogels, TAA-SLN carbomer gel resulted in higher drug permeation amount and drug deposition withinporcine ear skin after 24 h penetration experiment. Conclusion TAA-SLN carbomer gel is preparedwith stable physicochemical properties. The release profile and improved drug permeation into skinmake it be a promising vehicle for transdermal drug delivery.

Preparation and characterization of icariin/PHBV drug delivery coatings on anodic oxidized titanium

A composite material was fabricated by applying a biodegradable drug delivery coating,consisting of poly（3-hydroxyburyrate-co-3-hydroxyvalerate）（PHBV） and icariin,to an anodic oxidized titanium plate.The coating was prepared by evaporating chloroform solution containing PHBV and icariin on the titanium plate under vacuum condition.Icariin/PHBV coated titanium plates significantly enhance the proliferation of MG-63 cells compared with the PHBV coated and anodic oxidized ones.Increased icariin contained in the coating displays an elevated influence on cell proliferation.The results show that icariin gradually releases from the coating to cells mainly through the phospholipid-based cellular membrane instead of the culture medium.The overall results suggest that the novel icariin/PHBV coating can be used to enhance the bioactivity of titanium based orthopedic implants.

Design and preparation of a new multi-targeted drug delivery system using multifunctional nanoparticles for co-delivery of siRNA and paclitaxel

Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel(PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid(FA) and glucose(Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCopolyethyleneimine(FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol(PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu(NPsB) and FeCo-PEI-PLA-PEG-FA/Glu(NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX.Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.

Enhanced intestinal lymphatic absorption of saquinavir through supersaturated self-microemulsifying drug delivery systems

The therapeutic potential of saquinavir, a specific inhibitor of human immunodeficiency virus(HIV)-1 and HIV-2 protease enzymes, has been largely limited because of a low solubility and consequnt low bioavailability. Thus, we aimed to design a supersaturated selfmicroemulsifying drug delivery system(S-SMEDDS) that can maintain a high concentration of saquinavir in gastro-intestinal fluid thorugh inhibiting the drug precipitation to enhance the lymphatic transport of saquinavir and to increase the bioavailability of saquinavir considerably. Solubilizing capacity of different oils, surfactants, and cosurfactants for saquinavir was evaluated to select optimal ingredients for preparation of SMEDDS.Through the construction of pseudo-ternary phase diagram, SMEDDS formulations were established. A polymer as a precipitation inhibitor was selected based on its viscosity and drug precipitation inhibiting capacity. The S-SMEDDS and SMEDDS designed were administered at an equal dose to rats. At predetermined time points, levels of saquinavir in lymph collected from the rats were assessed. SMEDDS prepared presented a proper selfmicroemulsification efficiency and dispersion stability. The S-SMEDDS fabricated using the SMEDDS and hydroxypropyl methyl cellulose 2910 as a precipitation inhibitor exhibited a signficantly enhanced solubilizing capacity for saquinavir. The drug concentration in a simulated intestinal fluid evaluated with the S-SMEDDS was also maintained at higher levels for prolonged time than that examined with the SMEDDS. The S-SMEDDS showed a considerably enhanced lymphatic absoprtion of saquinavir in rats compared to the SMEDDS.Therefore, the S-SMEDDS would be usefully exploited to enhance the lymphatic absorption of hydrophobic drugs that need to be targeted to the lymphatic system.

Alginate-Coated Fe3O4 Hollow Microspheres for Drug Delivery

Novel hollow Fe3O4 nanoparticles for drug delivery were synthesized via a one-step template- free approach. These nanoparticles were obtained by modifing the Fe3O4 nanoparticles with 3-aminopropyltrimethoxy silane, and then grafting alginate onto the surface of amine magnetic. The hollow structure of Fe3O4 spheres was characterized by TEM, XRD, and XPS. The M-H hysteresis loop indicated that the magnetic spheres exhibit snperparamagnetic characteristics at room temperature. Daunorubicin acting as a model drug was loaded into the carrier, and the maximum percent of envelop and load were 28.4% and 14.2% respectively. The drug controlled releasing behaviors of the carriers were compared in different pH media.

A Study on the Multi-Compartment Linear Circulation Pharmacokinetic Model for the Targeting Drug Delivery System

By analyzing the observed phenomena and the data collected in the study, a multi-compartment linear circulation model for targeting drug delivery system was developed and the function formulas of the drug concentration-time in blood and target organ by computing were figured out. The drug concentration-time curve for target organ can be plotted with reference to the data of drug concentration in blood according to the model. The pharmacokinetic parameters of the drug in target organ could also be obtained. The practicability of the model was further checked by the curves of drug concentration-time in blood and target organ(liver) of liver-targeting nanoparticles in animal tests. Based on the liver drug concentration-time curves calculated by the function formula of the drug in target organ, the pharmacokinetic behavior of the drug in target organ(liver) was analyzed by statistical moment, and its pharmacokinetic parameters in liver were obtained. It is suggested that the (relative targeting index( can be used for quantitative evaluation of the targeting drug delivery systems.

Narrative review-drug delivery in age-related macular degeneration

This narrative review highlights routes of ocular drug delivery for age-related macular degeneration(AMD).AMD is the leading cause of irreversible blindness in industrialized countries and accounts for 8.7%of blindness worldwide.Advanced AMD can be classified into two subtypes:late-stage dry AMD[known as geographic atrophy(GA)]and neovascular AMD(nAMD).GA is often bilateral and results from progressive and irreversible loss of photoreceptors and areas of the retinal pigment epithelium.Wet AMD is characterized by angiogenesis from the choroid to the normally avascular regions underneath the retinal pigment epithelium(RPE)or retina,a process known as choroidal neovascularization(CNV).Various targeted therapeutic options are currently available to reduce the progression rate and maintain vision in patients with nAMD.Intravitreal delivery of anti-VEGF protein treatments to halt CNV is currently the gold-standard of care for nAMD.Subretinal and suprachoroidal delivery approaches are also being explored for gene and molecular therapies.Advancements in nanotechnology and biomaterials have also led to the development of microscopic drug delivery systems,including hydrogels,microparticles,nanoparticles,implants,and liposomes.Gene therapy and stem cell therapy has recently emerged as a potential candidate treatment modality for AMD and other retinal degenerations.New drug targets and modalities have stimulated exciting developments in ocular drug delivery with the promise of greater efficacy and durability of AMD treatment.

Synthesis of an Amphiphilic Dendrimer-Like Block Copolymer and Its Application on Drug Delivery

Dendrimer-like amphiphilic copolymer is a kind of three-dimensional spherical structure polymer. An amphiphilic dendrimer-like diblock copolymer, PEEGE-G2-b-PEO（OH）12, constituted of a hydrophobic poly（ethoxyethyl glycidol ether） inner core and a hydrophilic poly（ethylene oxide） outer layer, has been successfully synthesized by the living anionic ring-opening polymerization method. The intermediates and targeted products were charac-terized with 1H NMR spectroscopy and gel permeation chromatography. The application on drug delivery of dendrimer-like diblock copolymer PEEGE-G2-b-PEO（OH）12 using DOX as a model drug was also studied. The drug loading content and encapsulation e ciency were found at 13.07% and 45.75%, respectively. In vitro release experiment results indicated that the drug-loaded micelles exhibited a sustained release behavior under acidic media.

A review on phospholipids and their main applications in drug delivery systems

Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity.These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems.The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems,and highlight the relationship between the properties and applications,and the effect of the species of phospholipids on the efficiency of drug delivery.We refer to some relevant literatures,starting from the structures,main sources and properties of phospholipids to introduce their applications in drug delivery systems.The present article focuses on introducing five types of carriers based on phospholipids,including liposomes,intravenous lipid emulsions,micelles,drug-phospholipids complexes and cochleates.

Metal-Organic Framework Nanocarriers for Drug Delivery in Biomedical Applications

Investigation of metal–organic frameworks(MOFs)for biomedical applications has attracted much attention in recent years.MOFs are regarded as a promising class of nanocarriers for drug delivery owing to well-defined structure,ultrahigh surface area and porosity,tunable pore size,and easy chemical functionalization.In this review,the unique properties of MOFs and their advantages as nanocarriers for drug delivery in biomedical applications were discussed in the first section.Then,state-ofthe-art strategies to functionalize MOFs with therapeutic agents were summarized,including surface adsorption,pore encapsulation,covalent binding,and functional molecules as building blocks.In the third section,the most recent biological applications of MOFs for intracellular delivery of drugs,proteins,and nucleic acids,especially aptamers,were presented.Finally,challenges and prospects were comprehensively discussed to provide context for future development of MOFs as efficient drug delivery systems.

A Review on Nano-Based Drug Delivery System for Cancer Chemoimmunotherapy

Although notable progress has been made on novel cancer treatments,the overall survival rate and therapeutic effects are still unsatisfactory for cancer patients.Chemoimmunotherapy,combining chemotherapeutics and immunotherapeutic drugs,has emerged as a promising approach for cancer treatment,with the advantages of cooperating two kinds of treatment mechanism,reducing the dosage of the drug and enhancing therapeutic effect.Moreover,nano-based drug delivery system(NDDS)was applied to encapsulate chemotherapeutic agents and exhibited outstanding properties such as targeted delivery,tumor microenvironment response and site-specific release.Several nanocarriers have been approved in clinical cancer chemotherapy and showed significant improvement in therapeutic efficiency compared with traditional formulations,such as liposomes(Doxil R,Lipusu R),nanoparticles(Abraxane R)and micelles(Genexol-PM R).The applications of NDDS to chemoimmunotherapy would be a powerful strategy for future cancer treatment,which could greatly enhance the therapeutic efficacy,reduce the side effects and optimize the clinical outcomes of cancer patients.Herein,the current approaches of cancer immunotherapy and chemoimmunotherapy were discussed,and recent advances of NDDS applied for chemoimmunotherapy were further reviewed.

Targeting and exploitation of tumor-associated neutrophils to enhance immunotherapy and drug delivery for cancer treatment

Neutrophils,the most abundant leukocytes in human blood,are essential fighter immune cells against microbial infection.Based on the finding that neutrophils can either restrict or promote cancer progression,tumor-associated neutrophils(TAN)are classified into anti-tumor N1 and pro-tumor N2 subsets.One of the major mechanisms underlying the tumor-promoting function of N2-TANs is suppression of adaptive immune cells,in particular,cytotoxic T lymphocytes.Currently,no established methodologies are available that can unequivocally distinguish immunosuppressive TANs and granulocytic/polymorphonuclear myeloid-derived suppressor cells(G/PMN-MDSC).In view of the critical role of PMN-MDSCs in immune evasion and resistance to cancer immunotherapy,as established from data obtained with diverse cancer models,therapeutic strategies targeting these cells have been actively developed to enhance the efficacy of immunotherapy.Here,we have reviewed the available literature on strategies targeting PMN-MDSCs and summarized the findings into four categories:(1)depletion of existing PMN-MDSCs,(2)blockade of the development of PMNMDSCs,(3)blockade of PMN-MDSC recruitment,(4)inhibition of immunosuppressive function.Owing to their high mobility to inflamed organs and ability to trespass the blood-brain barrier,neutrophils are outstanding candidate carriers in nanoparticle-based therapies.Another attractive application of neutrophils in cancer therapy is the use of neutrophil membrane-derived nanovesicles as a surrogate of extracellular vesicles for more efficient and scalable drug delivery.In the second part of the review,we have highlighted recent advances in the field of neutrophil-based cancer drug delivery.Overall,we believe that neutrophil-based therapeutics are a rapidly growing area of cancer therapy with significant potential benefits.

Recent progress on nanoparticle-based drug delivery systems for cancer therapy

The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, poor water solubility, and limited bioavailability. Nanoparticles with tuned size and surface characteristics are the key components of nanotherapeutics, and are designed to passively or actively deliver anti-cancer drugs to tumor cells. We provide an overview of nanoparticle-based drug delivery methods and cancer therapies based on tumor-targeting delivery strategies that have been developed in recent years.

Nanoparticle–Cartilage Interaction: Pathology-Based Intra-articular Drug Delivery for Osteoarthritis Therapy

Osteoarthritis is the most prevalent chronic and debilitating joint disease,resulting in huge medical and socioeconomic burdens.Intra-articular administration of agents is clinically used for pain management.However,the effectiveness is inapparent caused by the rapid clearance of agents.To overcome this issue,nanoparticles as delivery systems hold considerable promise for local control of the pharmacokinetics of therapeutic agents.Given the therapeutic programs are inseparable from pathological progress of osteoarthritis,an ideal delivery system should allow the release of therapeutic agents upon specific features of disorders.In this review,we firstly introduce the pathological features of osteoarthritis and the design concept for accurate localization within cartilage for sustained drug release.Then,we review the interactions of nanoparticles with cartilage microenvironment and the rational design.Furthermore,we highlight advances in the therapeutic schemes according to the pathology signals.Finally,armed with an updated understanding of the pathological mechanisms,we place an emphasis on the development of“smart”bioresponsive and multiple modality nanoparticles on the near horizon to interact with the pathological signals.We anticipate that the exploration of nanoparticles by balancing the efficacy,safety,and complexity will lay down a solid foundation tangible for clinical translation.

Structure-Property Relationships and Models of Controlled Drug Delivery of Biodegradable Poly (D, L-lactic acid) Microspheres

An oil-in-water (O/W) solvent evaporation method was used to prepare biodegradable microspheresbased on poly(D,L-lactic acid) (PLA). Nifedipine, a hydrophobic drug, was chosen as a model molecule in the studyof drug entrapment and release. Effect of preparation conditions on the size, morphology, drug loading, and releaseprofiles of micropheres was investigated. Based on in vitro release experimental findings, a diffusion/dissolutionmodel was presented for quantitative description of the resulting release behaviors and drug release kinetics fromPLA microspheres analyzed. The mathematical models were used to predict the effect of microstructure on theresulting drug release. It provided an approach to determine the suitable structure parameters for microspheres toachieve desired drug release behaviors.