Conventional Drug Delivery Systems Research Articles

Microencapsulation of Ionic Liquid by Interfacial Self-Assembly of Metal-Phenolic Network for Efficient Gastric Absorption of Oral Drug Delivery.

Improving bioavailability of orally delivered drugs is still challenging, as conventional drug delivery systems suffer from non-specific drug delivery in the gastrointestinal (GI) tract and limited drug absorption efficiency. Gastric drug delivery is even more difficult due to the harsh microenvironment, short retention time, and physiologic barriers in the stomach. Here, an oral drug delivery microcapsule system was developed for gastric drug delivery, which consists of ionic liquid (IL) as the inner carrier and metal-phenolic network (MPN) as the microcapsule shell. The IL@MPN microcapsules are prepared by interfacial self-assembly of FeIII and quercetin at the interface of hydrophobic IL ([EMIM][NTf2]) and water. The formation of MPN shell could improve the stability of IL droplets in water and endow the system with pH-response drug release properties, while the encapsulated IL core could efficiently load the drug and enhance the drug tissue permeability. The IL@MPN microcapsules showed enhanced drug absorption in the stomach after oral administration in a rat model, where the microcapsules are disassembled in gastric acid, and the released IL could reduce the viscosity of mucus gel and increase the drug transport rate across endothelial cells. This work presents a simple yet efficient strategy for oral drug delivery to the stomach. Given the diversity and versatility of both MPN and IL, the proposed self-assembled microcapsules could expand the toolbox of drug delivery systems with enhanced oral drug bioavailability.

A mitochondria-targeted nano-platform for pancreatic cancer therapy.

Liposome is a conventional drug delivery system which has been widely used in the pharmacy field. However, its applications are greatly restricted in clinical practice by the disadvantages of cholesterol and nonselective distribution. Herein, a novel platform for anti-tumor drug delivery was developed by incorporating an amphiphilic stachydrine-octadecane conjugate (SS) as the mitochondria-targeting molecule onto the triptolide-liposome surfaces (SS-TP LPs). The polyethylene glycol (PEG) and the suitable particle size (about 133 nm) of liposomes facilitated their stabilities, the long half-life in blood and the escape from the rapid elimination. The SS-TP LPs were internalized and accumulated into the mitochondria of cancer cells in a time-dependent manner, followed by triggering permeabilization of the mitochondrial outer membrane by inhibiting Bcl-2, and then further caused greater cancer cell death via releasing cytochrome C and initiating a cascade of caspase 3 reactions. In the Pan02 tumor-bearing mice, the SS-TP LPs showed significant efficacy in inhibiting tumor growth and reducing tumor size but synchronously exhibited specific mitochondria-targeting and much lower subacute toxicity compared with the free TP and TP LPs. Our study suggests that SS-TP LPs can be a promising anticancer drug delivery system for mitochondria-targeted therapy in pancreatic cancer.

Cancer-Cell-Selective Targeting by Arylcyclopropylamine-Vorinostat Conjugates.

Anticancer drug delivery by small molecules offers a number of advantages over conventional macromolecular drug delivery systems. We previously developed phenylcyclopropylamine (PCPA)-drug conjugates (PDCs) as small-molecule-based drug delivery vehicles for targeting lysine-specific demethylase 1 (LSD1)-overexpressing cancers. In this study, we applied this PDC strategy to the HDAC-inhibitory anticancer agent vorinostat. Among three synthesized PCPA or arylcyclopropylamine (ACPA)-vorinostat conjugates 1, 9, and 32, conjugate 32 with a 4-oxybenzyl linker showed sufficient stability in buffer solutions, potent LSD1 inhibition, efficient LSD1-dependent vorinostat release, and potent and selective antiproliferative activity toward LSD1-expressing human breast cancer and small-cell lung cancer cell lines. These results indicate that the conjugate selectively releases vorinostat in cancer cells. A similar strategy may be applicable to other anticancer drugs.

Modulating Macrophage Clearance of Nanoparticles: Comparison of Small-Molecule and Biologic Drugs as Pharmacokinetic Modifiers of Soft Nanomaterials

Nanomedicines show benefits in overcoming the limitations of conventional drug delivery systems by reducing side effects, toxicity, and exhibiting enhanced pharmacokinetic (PK) profiles to improve the therapeutic window of small-molecule drugs. However, upon administration, many nanoparticles (NPs) prompt induction of host innate immune responses, which in combination with other clearance pathways such as renal and hepatic, eliminate up to 99% of the administered dose. Here, we explore a drug predosing strategy to transiently suppress the mononuclear phagocyte system (MPS), subsequently improving the PK profile and biological behaviors exhibited by a model NP system [hyperbranched polymers (HBPs)] in an immunocompetent mouse model. In vitro assays allowed the identification of five drug candidates that attenuated cellular association. Predosing of lead compounds chloroquine (CQ) and zoledronic acid (ZA) further showed increased HBP retention within the circulatory system of mice, as shown by both fluorescence imaging and positron emission tomography-computed tomography. Flow cytometric evaluation of spleen and liver tissue cells following intravenous administration further demonstrated that CQ and ZA significantly reduced HBP association with myeloid cells by 23 and 16%, respectively. The results of this study support the use of CQ to pharmacologically suppress the MPS to improve NP PKs.

Smart intraoral systems for advanced drug delivery

AbstractDrug administration through the oral cavity is considered to be a convenient, effective, and time‐saving strategy in the clinic with high safety and quick onset, especially for patients with needle fear and swallowing difficulties. Without the degradation in gastrointestinal tract and first‐pass metabolism, the intraoral drug delivery system turns out to be an attractive option for macromolecule absorption, which will provide a promising platform for the successful delivery of protein, peptide, nucleic acid, and polysaccharide. Nevertheless, limited bioavailability, short retention time, and poor reproducibility pose a major hurdle to the further application of conventional intraoral drug delivery systems. Recent advances in chemical, material, and engineering techniques bring great opportunities to improve intraoral system fabrication and applications, owing to the high biocompatibility and functional diversity. In this review, we systematically summarize the recent development of smart intraoral drug delivery systems, including fast dissolving oral films, medicinal chewing gum systems, intraoral mucoadhesive systems, physical assisted systems, intelligent intraoral device, and chemically assisted systems. Moreover, the challenges and prospects for clinical and industrial applications of current strategies are well discussed. It is believed that the smart intraoral system would serve as a promising candidate to improve human life in the near future.

Special Issue on the Development of Microfluidic Devices for Medical Applications

Microfluidics refers to the science of handling fluids in microstructures and has been widely used in the medical field to miniaturize conventional drug delivery systems, bioassays, and diagnostics [...]

Genetically Engineered Viral Vectors and Organic-Based Non-Viral Nanocarriers for Drug Delivery Applications.

Conventional drug delivery systems are challenged by concerns related to systemic toxicity, repetitive doses, drug concentrations fluctuation, and adverse effects. Various drug delivery systems are developed to overcome these limitations. Nanomaterials are employed in a variety of biomedical applications such as therapeutics delivery, cancer therapy, and tissue engineering. Physiochemical nanoparticle assembly techniques involve the application of solvents and potentially harmful chemicals, commonly at high temperatures. Genetically engineered organisms have the potential to be used as promising candidates for greener, efficient, and more adaptable platforms for the synthesis and assembly of nanomaterials. Genetically engineered carriers are precisely designed and constructed in shape and size, enabling precise control over drug attachment sites. The high accuracy of these novel advanced materials, biocompatibility, and stimuli-responsiveness, elucidate their emerging application in controlled drug delivery. The current article represents the research progress in developing various genetically engineered carriers. Organic-based nanoparticles including cellulose, collagen, silk-like polymers, elastin-like protein, silk-elastin-like protein, and inorganic-based nanoparticles are discussed in detail. Afterward, viral-based carriers are classified, and their potential for targeted therapeutics delivery is highlighted. Finally, the challenges and prospects of these delivery systems are concluded.

AN OVERVIEW ON AQUASOMES : A NOVEL APPROACH FOR DELIVERING MACROMOLECULES

In recent blossoming era of research in nanobiotechnology, aquasomes are viewed as an effective and efficient carrier system for drug delivery or biochemically active long chain macromolecules like protein and peptide, different hormones, antigens, enzymes and gene delivery. Aquatones are spherical in shape and having particle size within 60- 300nm. Self-assembled structure of aquasome (due to its natural property) it generates a focus on nanobiotechnology research as a carrier system. Mainly, aquasomes contain three-layers, that is core material, coating material, drug layer attached by ionic or non-covalent bond. Aquasomes include mainly the core materials like , hydroxyapatite, solid phase nanocrystalline ceramic diamond (carbon) and calcium phosphate dihydrate(brushite) . The coating of core material is done with glassy polyhydroxyl oligomeric film such as cellobiose and trehalose, on which modification of biochemically active molecules are attached. Whereas, calcium phosphate used as a core material, because of it is naturally present in the body. Whether calcium phosphate is unstable in nature, due to prolong storage it converts into hydroxyapatite which is a better core than calcium phosphate to develop the aquasomes. The solid core material renders stability of structures, while the coating material stabilizes the biochemically active molecules and protects against dehydration. In this review, we tried to an overview of aquasomes, and about its advantages over conventional drug delivery system, shielding effect of aquasomes on desired drug and how its self-assembled structures, makes them an attractive carrier to deliver biochemically active molecules.

Effect of formulation variables on the characteristics of vildagliptin microspheres

Vildagliptin, an antihyperglycemic drug, is having high water solubility and shorter elimination half-life. This leads to administer vildagliptin frequently to maintain its therapeutic efficacy. So the Formulation of vildagliptin microspheres might be beneficial in overcoming the side effects of the conventional drug delivery systems during the prolonged treatment. The aim of the work was to evaluate and fabricate the microspheres, which improved the absorption of drug and increase the release kinetics and also to study the effect of formulation variables. The microspheres of vildagliptin were formulated by solvent evaporation technique. The formulation variables were the concentration of Ethyl cellulose (EC), Polyvinyl alcohol (PVA), and stirring speed. The resulting microspheres were evaluated for percentage yield, percentage entrapment efficiency, particle size, surface morphology, drug release rates. The morphological structure of the microspheres revealed spherical shaped structures. Good entrapment were observed. The in vitro drug release was found to be controlled. Results indicated that physicochemical properties of microspheres strongly affected by the presence of drug/polymer ratios, changing the concentrations of them and effect of variables.

The Impact of the Oil Phase Selection on Physicochemical Properties, Long-Term Stability, In Vitro Performance and Injectability of Curcumin-Loaded PEGylated Nanoemulsions.

A nanotechnology-based approach to drug delivery presents one of the biggest trends in biomedical science that can provide increased active concentration, bioavailability, and safety compared to conventional drug-delivery systems. Nanoemulsions stand out amongst other nanocarriers for being biodegradable, biocompatible, and relatively easy to manufacture. For improved drug-delivery properties, longer circulation for the nanoemulsion droplets should be provided, to allow the active to reach the target site. One of the strategies used for this purpose is PEGylation. The aim of this research was assessing the impact of the oil phase selection, soybean or fish oil mixtures with medium chain triglycerides, on the physicochemical characteristics and injectability of curcumin-loaded PEGylated nanoemulsions. Electron paramagnetic resonance spectroscopy demonstrated the structural impact of the oil phase on the stabilizing layer of nanoemulsions, with a more pronounced stabilizing effect of curcumin observed in the fish oil nanoemulsion compared to the soybean oil one. The design of the experiment study, employed to simultaneously assess the impact of the oil phase, different PEGylated phospholipids and their concentrations, as well as the presence of curcumin, showed that not only the investigated factors alone, but also their interactions, had a significant influence on the critical quality attributes of the PEGylated nanoemulsions. Detailed physicochemical characterization of the NEs found all formulations were appropriate for parenteral administration and remained stable during two years of storage, with the preserved antioxidant activity demonstrated by DPPH and FRAP assays. In vitro release studies showed a more pronounced release of curcumin from the fish oil NEs compared to that from the soybean oil ones. The innovative in vitro injectability assessment, designed to mimic intravenous application, proved that all formulations tested in selected experimental setting could be employed in prospective in vivo studies. Overall, the current study shows the importance of oil phase selection when formulating PEGylated nanoemulsions.

Design and Development of Pharmacosome Loaded with Piroxicam to Improve Oral Bioavailability

The design of the present investigation was to prepare Piroxicam bounded pharmacosomes to improve the water solubility, bioavailability and to minimize the gastrointestinal toxicity of Piroxicam. Pharmacosome is a potential approach in vesicular drug delivery systems which exhibits several advantages over conventional vesicular drug delivery systems. Pharmacosomes are phospholipid complexes with a potential to improve bioavailability of poorly water soluble as well as poorly lipophilic drugs. Piroxicam was complexed with soya phosphatidylcholine in various ratios using conventional solvent evaporation technique. In our study, Pharmacosomes thus prepared were subjected to drug solubility, drug content evaluation, surface morphology (by scanning electron microscopy), crystallinity (by X- ray powder diffraction), quality control tests for capsules and in-vitro dissolution study. Solubility profile of the prepared complexes was found to be much better than Piroxicam pure drug. This improvement in solubility of the prepared pharmacosomes may result in improved dissolution and lower gastrointestinal toxicity. Drug content was found to be 96.84%w /W for the optimized Piroxicam phospholipid complex, F1 (Piroxicam: lecithin ratio of 1:1). The pharmacosomes were found to be disc shaped in scanning electron microscopy. X-ray powder diffraction data confirmed the formation of phospholipid complexes. The formulation F1 showed 94.69% drug release while the free Piroxicam showed a total of only 60.42% at the end of 10-hour dissolution study. Thus the solubility and hence the bioavailability of Piroxicam can be increased to a greater extent by complexing it with soya phosphatidylcholine.

3D-printed reservoir-type implants containing poly(lactic acid)/poly(caprolactone) porous membranes for sustained drug delivery.

Implantable drug delivery systems are an interesting alternative to conventional drug delivery systems to achieve local or systemic drug delivery. In this work, we investigated the potential of fused-deposition modelling to prepare reservoir-type implantable devices for sustained drug delivery. An antibiotic was chosen as a model molecule to evaluate the potential of this type of technology to prepare implants on-demand to provide prophylactic antimicrobial treatment after surgery. The first step was to prepare and characterize biodegradable rate-controlling porous membranes based on poly(lactic acid) (PLA) and poly(caprolactone) (PCL). These membranes were prepared using a solvent casting method. The resulting materials contained different PLA/PCL ratios. Cylindrical implants were 3D-printed vertically on top of the membranes. Tetracycline (TC) was loaded inside the implants and drug release was evaluated. The results suggested that membranes containing a PLA/PCL ratio of 50/50 provided drug release over periods of up to 25days. On the other hand, membranes containing lower PCL content did not show a porous structure and accordingly the drug could not permeate to the same extent. The influence of different parameters on drug release was evaluated. It was established that film thickness, drug content and implant size are critical parameters as they have a direct influence on drug release kinetics. In all cases the implants were capable of providing drug release for at least 25days. The antimicrobial properties of the implants were evaluated against E. coli and S. aureus. The resulting implants showed antimicrobial properties at day 0 and even after 21days against both type of microorganisms. Finally, the biocompatibility of the implants was evaluated using endothelial cells. Cells exposed to implants were compared with a control group. There were no differences between both groups in terms of cell proliferation and morphology.

Novel Nanotechnology-Based Approaches for Targeting HIV Reservoirs.

Highly active anti-retroviral therapy (HAART) is prescribed for HIV infection and, to a certain extent, limits the infection’s spread. However, it cannot completely eradicate the latent virus in remote and cellular reservoir areas, and due to the complex nature of the infection, the total eradication of HIV is difficult to achieve. Furthermore, monotherapy and multiple therapies are not of much help. Hence, there is a dire need for novel drug delivery strategies that may improve efficacy, decrease side effects, reduce dosing frequency, and improve patient adherence to therapy. Such a novel strategy could help to target the reservoir sites and eradicate HIV from different biological sanctuaries. In the current review, we have described HIV pathogenesis, the mechanism of HIV replication, and different biological reservoir sites to better understand the underlying mechanisms of HIV spread. Further, the review deliberates on the challenges faced by the current conventional drug delivery systems and introduces some novel drug delivery strategies that have been explored to overcome conventional drug delivery limitations. In addition, the review also summarizes several nanotechnology-based approaches that are being explored to resolve the challenges of HIV treatment by the virtue of delivering a variety of anti-HIV agents, either as combination therapies or by actively targeting HIV reservoir sites.

Formulation and optimization of Paliperidone palmitate biodegradable injectable microspheres using Box-Behnken design

The objective of study was to formulate and optimize poly lactic-co-glycolic acid based long-acting injectable microspheres of Paliperidone palmitate (PP) using Box- Behnken design for treatment of schizophrenia. The oral bioavailability of PP is 28%, it necessitates the formulation of PP in injectable dosage form. In this study, PP microspheres were manufactured using oil in water (O/W) emulsion solvent evaporation technique. Box-Behnken design was selected to study effect of independent variables (X) on dependent variables (Y). Independent variables in this study were drug: polymer ratio (X1), homogenization speed (X2), rate of addition (X3). While mean particle size (Y1), drug loading (Y2), entrapment efficiency (Y3), burst release (Y4) and drug release on day 21 (Y5) were considered as dependent variables. The statistical evaluation of data was performed by using Design Expert software. Size of formulated microspheres was studied using laser diffraction technique. The shape of particles was determined using digital microscope and scanning electron microscopy (SEM). Drug release was studied using controlled temperature shaking water bath apparatus. Fourier transforms infrared spectroscopy (FTIR) and differential scanning calorimetric (DSC) study was carried out to detect any incompatibility. Nuclear magnetic resonance (NMR) techniques were used to characterize end cap and monomer ratio in developed microspheres. The prepared PP microspheres exhibited smooth surface and spherical shape. Box-Behnken design was employed for optimization of microspheres. Mean particle size of prepared PP microspheres was found to be in between 12 ± 3.7 μm and 152 ± 3.4 μm. Drug loading in prepared microspheres was found in between 19.4 ± 0.2% to 46.5 ± 0.7%. Entrapment efficiency of prepared microspheres was obtained between 58.6 ± 0.8% and 96.8 ± 1.4%. Drug release from PP microspheres was observed as near zero order. The observed and predicted values of all responses were in close agreement with each other. End cap analysis and molar ratio of Lactic acid: Glycolic acid for formulated microspheres was found to be ester end cap and ∼75:25 respectively. The optimized PP microspheres were capable of releasing drug in vitro up to 28 days. The optimized novel PP injectable microspheres are having profound advantages over conventional oral drug delivery systems in treatment of schizophrenia.

Mesoporous silica nanocarriers as drug delivery systems for anti-tubercular agents: a review.

The treatment and management of tuberculosis using conventional drug delivery systems remain challenging due to the setbacks involved. The lengthy and costly treatment regime and patients' non-compliance have led to drug-resistant tuberculosis, which is more difficult to treat. Also, anti-tubercular drugs currently used are poor water-soluble drugs with low bioavailability and poor therapeutic efficiency except at higher doses which causes drug-related toxicity. Novel drug delivery carrier systems such as mesoporous silica nanoparticles (MSNs) have been identified as nanomedicines capable of addressing the challenges mentioned due to their biocompatibility. The review discusses the sol–gel synthesis and chemistry of MSNs as porous drug nanocarriers, surface functionalization techniques and the influence of their physico-chemical properties on drug solubility, loading and release kinetics. It outlines the physico-chemical characteristics of MSNs encapsulated with anti-tubercular drugs.

Athlete’s foot disease: A comparative study on marketed products

An infection of the foot with fungi, such as the Athlete’s foot, is frequently observed globally, both in men and women. In the present review, different marketed products used in treating Athlete's foot disease were critically analysed and compared. The marketed products include Oral medications and Topical medications like creams, gels, dusting powders, and sprays to meet the needs of Athlete's foot disease patients. Oral products are prescribed only when topical treatments are unsuccessful and the infection becomes systemic or deep-rooted. They may cause mild side effects like nausea, dizziness, and digestive problems to serious side effects like liver damage. In comparison to oral medications, topical fungal therapy is usually preferred due to no systemic side effects, ability to bypass first-pass metabolism, and minimum toxicity. Gels are preferred over creams for being effective and easily washable. With powders, moisture retention may delay the healing process leading to secondary infections with bacteria. Sprays can release the drug easily in hard-to-reach corners of the body. However, propellants used in them are inflammable, and the products are expensive. Oral products are best for treating chronic infections despite their side effects, and topicals are suitable for mild infections, with sprays being the most convenient formulation. Several studies have indicated that topical nanocarriers with antifungal agents display superior therapeutic efficacy and minimal toxicity due to their ability to overcome challenges associated with conventional drug delivery systems like poor retention and low bioavailability. There is a good scope for developing topical nanocarrier-based antifungal formulations to treat Athlete's foot disease with minimum side effects effectively. 
 Keywords: Athlete’s foot disease, Orals, Topicals, Creams, Gels, Powders, Sprays.

A Review Article on Dissolution Studies in Novel Drug Delivery System

In present days there is immense advancement in drug delivery despite novel drug delivery has become civilized as pharmaceutical scientists has worked hard over it. However the vocal pathway remnant the excellent pathway is for administration whereas the new drugs achieve the great patient compliance. The dissolution studies in NDDS have limit literature also and to still found locate inside the pharmacopeia. The dissolution studies is highly and commonly recommended for the solid dosage forms now a days it’s indeed enlarged to the other pharmaceutical formulations like suspensions, patches etc .The dissolution tactic is indeed an perfect tool such as maintaining batch-batch evaluation tests and also to analyze the drug release in vivo conditions. In sustained release the products that are obtained has several advantages in optimizing bio pharmaceutics and pharmacokinetics as compared to the conventional drug delivery systems.
 Keywords: Dissolution, sustained release, pharmacokinetics

Enhanced Antifungal and Wound Healing Efficacy of Statistically Optimized, Physicochemically Evaluated Econazole-Triamcinolone Loaded Silica Nanoparticles.

Co-encapsulated econazole nitrate-triamcinolone acetonide loaded biocompatible, physically stable, and non-irritating mesoporous silica nanoparticles (EN-TA–loaded MSNs) were prepared and optimized by using a central composite rotatable design (CCRD) for providing better therapeutic efficacy against commonly prevailed resistant fungal infections. These drugs loaded MSNs can significantly overcome the deficiencies and problems like short duration of action, requirement of frequent administration, erythema, and burning sensation and irritation associated with conventional drug delivery systems. The stability of optimized drugs loaded MSNs prepared with 100 gm of oil at pH 5.6 with a stirring time of 2 h was confirmed from a zeta potential value of −25 mV. The remarkable compatibility of formulation ingredients was depicted by X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR) spectra while scanning electron microscopy (SEM) and size analysis represented a very fine size distribution of nanoparticles ranging from 450–600 nm. The CCRD clearly predicted that the optimized parameters of drugs loaded MSNs have better values of percentage yield (85%), EN release (68%), and TA release (70%). Compared to pure drugs, the decreased cytotoxicity of EN-TA–loaded MSNs was quite evident because they showed a cell survival rate of 90%, while in the case of pure drugs, the survival rate was 85%. During in vivo antifungal testing against Candida albicans performed on three different groups, each consisting of six rabbits, the EN-TA–loaded MSNs were relatively superior in eradicating the fungal infection as a single animal exhibited a positive culture test. Rapid recovery of fungal infection and a better therapeutic effect of EN-TA–loaded MSN were quite evident in wound healing and histopathology studies. Likewise, on the 14th day, a larger inhibitory zone was measured for optimized nanoparticles (15.90 mm) compared to the suspension of pure drugs (13.90 mm). In skin irritation studies, MSNs did not show a grade of erythema compared to pure drugs, which showed a four-fold grade of erythema. As a result, MSNs loaded with combination therapy seem to have the potential of improving patient compliance and tolerability by providing enhanced synergistic antifungal effectiveness at a reduced dose with accelerated wound healing and reduced toxicity of therapeutics.

Cell-based carrier for targeted hitchhiking delivery.

Drug delivery systems aim at improving drug transport efficiency and therapeutic efficacy by rational design, and current research on conventional delivery systems brings new developments for disease treatment. Recently, studies on cell-based drug delivery systems are rapidly emerging, which shows great advantages in comparison to conventional drug delivery system. The system uses cells as carriers to delivery conventional drugs or nanomedicines and shows good biocompatibility and enhanced targeting efficiency, beneficial from self component and its physiological function. The construction methodology of cell-based carrier determines the effect on the physiological functions of transporting cell and affects its clinical application. There are different strategies to prepare cell-based carrier, such as direct internalization or surface conjugation of drugs or drug loaded materials. Thus, it is necessary to fully understand the advantages and disadvantages of different strategies for constructing cell-based carrier and then to seek the appropriate construction methodology for achieving better therapeutic results based on disease characterization. We here summarize the application of different types of cell-based carriers reported in recent years and further discuss their applications in disease therapy and the dilemmas faced in clinical translation. We hope that this summary can accelerate the process of clinical translation by promoting the technology development of cell-based carrier.

Biomimetic Nanoparticle Drug Delivery Systems to Overcome Biological Barriers for Therapeutic Applications.

Targeted drug delivery using nanoparticles has been applied for the treatment of diverse diseases, including cancer and inflammatory diseases. Nanoparticle-mediated delivery of therapeutic agents via the enhanced permeability and retention effect generally augments their therapeutic efficiency; however, limitations with passive entry of nanoparticles into diseased sites, due to the presence of biological barriers represented by the endothelial layer, remain to be addressed. To this end, development of nanoparticles with intrinsic characteristics similar to circulatory cells (e.g., leukocytes, platelets) for use as biomimetic drug delivery systems (DDS) has been focused as a means to overcome the issues of conventional DDS. In particular, synthetic biomimetic nanoparticles coated with cellular membranes were recently prepared and shown to actively overcome the inflamed vessels and tumor microenvironment as a result of the functionality of membrane proteins, which allowed secure drug delivery into diseased sites. We recently developed liposomes modified with leukocyte membrane proteins via intermembrane protein transfer, a simple method to reconstitute cellular membrane proteins onto lipid bilayers. The resultant liposomes demonstrated the ability to cross the inflamed endothelial layer and permeate into tumor tissue by mimicking the properties of leukocytes. Thus, biomimetic DDS offer promise as new therapeutic approaches for various diseases by overcoming biological barriers that typically inhibit drug delivery. Herein, we review recent approaches to develop biomimetic DDS using the cell membrane coating method, and highlight our recent findings on leukocyte-mimetic liposomes prepared via intermembrane protein transfer.