1.Advances in inhalable nano-formulations.
Yinjia LUO ; Xiao YUE ; Ziyu ZHAO ; Xuejuan ZHANG
Journal of Zhejiang University. Medical sciences 2025;54(4):511-521
Nano-drug delivery systems offer significant benefits, including high specific surface area, structural and functional diversity, and surface modifiability. When formulated as inhalable nano-formulation, these can not only enable precise pulmonary drug delivery but also improve pulmonary bioavailability and enhance thera-peutic efficacy. Currently, there are four types of inhalable nano-formulations for the treatment of respiratory diseases. Inhalable liquid preparations exhibit facile manufactur-ability and broad applicability yet demonstrate compromised stability during aerosolization. Through structure optimization, surface modification, dispersion medium optimization and device improvement, the atomization stability of nano-drug has been enhanced. Pressurized metered-dose inhalers loaded with nano-drugs face technical challenges: conventional propellants may dissolve nano-carriers, whereas co-solvents like ethanol compromise delivery efficiency. Thus, it is necessary to develop novel propellants that provide thermodynamic stability and optimal delivery performance. Nano-drug formulations in dry powder inhalers exhibit relatively favorable physical stability, however, pulmonary delivery efficiency and nanoparticles integrity during processing remain problematic. Pulmonary delivery efficiency can be improved by employing strategies such as blending excipients to promote the re-dispersibility of nanoparticle agglomerates, optimizing the design of microcarrier, and innovating preparation processes. In contrast, soft mist inhalers are an ideal option for pulmonary delivery of nano-drugs owing to their gentle and efficient atomization properties to maintain nano-drug integrity. This review summarizes the inhalable nano-formulations and focuses on challenges and proposed strategies encoun-tered in integrating nano-drug delivery systems and inhalation drug delivery systems. It aims to provide references for the future development of inhalable nano-formulations.
Administration, Inhalation
;
Humans
;
Drug Delivery Systems/methods*
;
Nanoparticles
;
Dry Powder Inhalers
;
Nanoparticle Drug Delivery System
;
Drug Compounding
;
Metered Dose Inhalers
;
Drug Carriers
2.Harmonizing tradition and technology: Liposomal nanocarriers unlocking the power of natural herbs in Traditional Chinese Medicine.
Ibrahim SHAW ; Aaron Albert ARYEE ; Yimer Seid ALI ; George Frimpong BOAFO ; Jingjing TIAN ; Ronald MLAMBO ; Songwen TAN ; Chuanpin CHEN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(6):700-713
Natural herbs demonstrate significant therapeutic potential in managing chronic and complex diseases; however, their clinical application faces limitations due to low bioavailability, instability, toxicity, and herb-drug interactions. Furthermore, insufficient standardized evidence and global acceptance impede their widespread adoption. Liposomes, nanocarriers consisting of a phospholipid bilayer enclosing an aqueous core, present a promising approach for enhancing the pharmacokinetics and therapeutic efficacy of herbal compounds. These adaptable systems can encapsulate both hydrophilic and hydrophobic agents, enabling targeted drug delivery and enhanced stability. Moreover, liposomes can be modified to carry diagnostic and imaging agents, enabling precise disease detection and monitoring. While liposomes offer potential as an innovative delivery technology for herbal remedies, their application in Traditional Chinese Medicine (TCM) remains relatively unexplored. TCM, with its holistic, energy-based approach to health and organ function, presents distinct challenges regarding formulation and delivery. This review examines the therapeutic potential of herbal medicines, emphasizing how liposomes address delivery challenges within the TCM framework. It also investigates the integration of TCM with Western medical practices, demonstrating how liposomal systems may bridge these approaches. The review analyzes key formulation techniques for TCM-loaded liposomes, particularly the microfluidic method, which demonstrates superior control over particle size and encapsulation efficiency compared to conventional methods. The analysis addresses barriers to integrating liposomal delivery systems with TCM, including physicochemical properties, scalability issues, and regulatory challenges. Finally, this review provides strategic recommendations for overcoming these obstacles and identifies future research directions to maximize the potential of liposomal technology in enhancing TCM therapies.
Liposomes/chemistry*
;
Drugs, Chinese Herbal/administration & dosage*
;
Humans
;
Medicine, Chinese Traditional/methods*
;
Drug Delivery Systems
;
Drug Carriers/chemistry*
;
Animals
;
Nanoparticles/chemistry*
3.Active herbal ingredients and drug delivery design for tumor therapy: a review.
Jing HAN ; Yanxi SHEN ; Ruiying CAO ; Weiren WANG ; Jinao DUAN ; Jialun DUAN ; Chunjie BAO
Chinese Journal of Natural Medicines (English Ed.) 2024;22(12):1134-1162
Active herbal ingredients are gaining recognition for their potent anti-tumor efficacy, attributable to various mechanisms including tumor cell inhibition, immune system activation, and tumor angiogenesis inhibition. Recent studies have revealed that numerous anti-tumor herbal ingredients, such as ginsenosides, ursolic acid, oleanolic acid, and Angelica sinensis polysaccharides, can be utilized to develop smart drug carriers like liposomes, micelles, and nanoparticles. These carriers can deliver active herbal ingredients and co-deliver anti-tumor drugs to enhance drug accumulation at tumor sites, thereby improving anti-tumor efficacy. This study provides a comprehensive analysis of the mechanisms by which these active herbal ingredients-derived carriers enhance therapeutic outcomes. Additionally, it highlights the structural properties of these active herbal ingredients, demonstrating how their unique features can be strategically employed to design smart drug carriers with improved anti-tumor efficacy. The insights presented aim to serve as a reference and guide future innovations in the design and application of smart drug carriers for cancer therapy that leverage active herbal ingredients.
Humans
;
Neoplasms/drug therapy*
;
Drug Delivery Systems
;
Drug Carriers/chemistry*
;
Animals
;
Drugs, Chinese Herbal/therapeutic use*
;
Antineoplastic Agents, Phytogenic/administration & dosage*
;
Nanoparticles/chemistry*
;
Antineoplastic Agents/administration & dosage*
4.Factors affecting nasal drug delivery and design strategies for intranasal drug delivery.
Xiaoyun HU ; Xiao YUE ; Chuanbin WU ; Xuejuan ZHANG
Journal of Zhejiang University. Medical sciences 2023;52(3):328-337
Intranasal drug delivery system is a non-invasive drug delivery route with the advantages of no first-pass effect, rapid effect and brain targeting. It is a feasible alternative to drug delivery via injection, and a potential drug delivery route for the central nervous system. However, the nasal physiological environment is complex, and the nasal delivery system requires "integration of medicine and device". Its delivery efficiency is affected by many factors such as the features and formulations of drug, delivery devices and nasal cavity physiology. Some strategies have been designed to improve the solubility, stability, membrane permeability and nasal retention time of drugs. These include the use of prodrugs, adding enzyme inhibitors and absorption enhancers to preparations, and new drug carriers, which can eventually improve the efficiency of intranasal drug delivery. This article reviews recent publications and describes the above mentioned aspects and design strategies for nasal intranasal drug delivery systems to provide insights for the development of intranasal drug delivery systems.
Administration, Intranasal
;
Drug Delivery Systems
;
Pharmaceutical Preparations
;
Drug Carriers
;
Brain
;
Nasal Cavity/physiology*
;
Nasal Mucosa
5.Preparation of Cangai oil transfersomes patches and its in vitro evaluation.
Kun ZHANG ; Lei XIONG ; Dan-Ye LI ; Jia-Ju GAO ; Yun-Kuan LIU ; Yun-Shu MA
China Journal of Chinese Materia Medica 2020;45(4):854-860
L_9(3~4) orthogonal experiment design was used to optimize the preparation of the patches,and investigate its affecting factors and skin irritation. Eugenol was taken as the index component to study the release behavior in vitro and percutaneous penetration of Cangai oil transfersomes patches by HPLC.The results showed that the optimal prescription for preparing Cangai oil transfersomes patches were Eudragit E100 0.6 g, succinic acid 0.08 g,triethyl citrate 0.25 g,glycerol 0.2 g.Patches prepared by the preferred preparation had a flat appearance without obvious bubbles.The initial adhesion was 18.33±2.52, the stickiness was(30.01±2.45) min,and the peel strength was(5.62±0.95) kN·m~(-1).The results of affecting factors experiment showed the order of factors affecting its adhesion was humidity>temperature>lighting,and the skin irritation test results showed no significant skin irritation after 24 h of single administration. The results of drug release behavior in vitro showed that the release and the percutaneous penetration of both Cangai oil patches and Cangai oil transfersomes patches conformed to the Higuchi equation.The release amount of eugenol were 80.66% and 82.25% at 72 h, with no significant difference. The cumulative permeation area of eugenol per unit area reached(0.195 6±0.065 9),(0.131 0±0.045 5) mg·cm~(-2) at 72 h, with significant differences(P<0.05).The experiment results proved that the preparation process of Cangai oil transfersomes patches was stable,and the prepared patches had a good adhesion. At the same time,the preparation of transfersomes patches could alleviate and control the release of the drug to a certain extent, and provide a certain experimental basis for clinical pediatric drug safety.
Administration, Cutaneous
;
Drug Carriers
;
Drug Liberation
;
Humans
;
Plant Oils/pharmacology*
;
Polymethacrylic Acids
;
Skin/drug effects*
;
Skin Absorption
;
Transdermal Patch
6.Application of nanodrug carriers in the prevention and treatment of infection around orthopedic prosthesis.
Zhenyao PAN ; Yan WANG ; Jiaojiao LI ; Jialong CHEN
Journal of Biomedical Engineering 2019;36(5):862-869
Despite the continuous improvement in perioperative use of antibiotics and aseptic techniques, the incidence of infection continues to rise as the need for surgery increasing and brings great challenges to orthopedic surgery. The rough or porous structure of the prosthesis provides an excellent place for bacterial adhesion, proliferation and biofilm formation, which is the main cause of infection. Traditional antibiotic therapy and surgical debridement are difficult to determine whether the infected focus have been removed completely and whether the infection will recur. In recent years, nanotechnology has shown obvious advantages in biomaterials and drug delivery. Nano drug carriers can effectively achieve local antimicrobial therapy, prevent surgical infection by local sustained drug release or intelligent controlled drug release under specific stimuli, and reduce the toxic side effects of drugs. The unique advantages of nanotechnology provide new ideas and options for the prevention and treatment of periprosthetic infection. At present, the application of nano-technology in the prevention and treatment of infection can be divided into the addition of nano-drug-loaded materials to prosthesis materials, the construction of drug-loaded nano-coatings on the surface of prosthesis, the perfusable nano-antimicrobial drug carriers, and the stimulation-responsive drug controlled release system. This article reviews the methods of infection prevention and treatment in orthopaedic surgery, especially the research status of nanotechnology in the prevention and treatment of periprosthetic infection.
Anti-Infective Agents
;
administration & dosage
;
Bacterial Adhesion
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Drug Carriers
;
Humans
;
Nanotechnology
;
Orthopedics
;
Prosthesis-Related Infections
;
prevention & control
7.Enhanced water solubility, antioxidant activity, and oral absorption of hesperetin by D-α-tocopheryl polyethylene glycol 1000 succinate and phosphatidylcholine.
Su-Fang GU ; Li-Ying WANG ; Ying-Jie TIAN ; Zhu-Xian ZHOU ; Jian-Bin TANG ; Xiang-Rui LIU ; Hai-Ping JIANG ; You-Qing SHEN
Journal of Zhejiang University. Science. B 2019;20(3):273-281
Hesperetin, an abundant bioactive component of citrus fruits, is poorly water-soluble, resulting in low oral bioavailability. We developed new formulations to improve the water solubility, antioxidant activity, and oral absorption of hesperetin. Two nano-based formulations were developed, namely hesperetin-TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) micelles and hesperetin-phosphatidylcholine (PC) complexes. These two formulations were prepared by a simple technique called solvent dispersion, using US Food and Drug Administration (FDA)-approved excipients for drugs. Differential scanning calorimetry (DSC) and dynamic light scattering (DLS) were used to characterize the formulations' physical properties. Cytotoxicity analysis, cellular antioxidant activity assay, and a pharmacokinetic study were performed to evaluate the biological properties of these two formulations. The final weight ratios of both hesperetin to TPGS and hesperetin to PC were 1:12 based on their water solubility, which increased to 21.5- and 20.7-fold, respectively. The hesperetin-TPGS micelles had a small particle size of 26.19 nm, whereas the hesperetin-PC complexes exhibited a larger particle size of 219.15 nm. In addition, the cellular antioxidant activity assay indicated that both hesperetin-TPGS micelles and hesperetin-PC complexes increased the antioxidant activity of hesperetin to 4.2- and 3.9-fold, respectively. Importantly, the in vivo oral absorption study on rats indicated that the micelles and complexes significantly increased the peak plasma concentration (Cmax) from 2.64 μg/mL to 20.67 and 33.09 μg/mL and also increased the area under the concentration-time curve of hesperetin after oral administration to 16.2- and 18.0-fold, respectively. The micelles and complexes increased the solubility and remarkably improved the in vitro antioxidant activity and in vivo oral absorption of hesperetin, indicating these formulations' potential applications in drugs and healthcare products.
Administration, Oral
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Animals
;
Antioxidants/chemistry*
;
Biological Availability
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Calorimetry, Differential Scanning
;
Dogs
;
Dose-Response Relationship, Drug
;
Drug Carriers
;
Female
;
Hep G2 Cells
;
Hesperidin/chemistry*
;
Humans
;
Light
;
Madin Darby Canine Kidney Cells
;
Micelles
;
Phosphatidylcholines/chemistry*
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Polyethylene Glycols/chemistry*
;
Rats
;
Rats, Sprague-Dawley
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Scattering, Radiation
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Solubility
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Solvents
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Vitamin E/chemistry*
;
Water/chemistry*
;
alpha-Tocopherol/chemistry*
8.Formulation development and evaluation of gastroretentive floating beads with Brucea javanica oil using ionotropic gelation technology.
Yue ZHANG ; Xi-Tong ZHANG ; Qi ZHANG ; Bing WANG ; Tong ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2018;16(4):293-301
In the present study, a gastric retention floating system for Brucea javanica oil, composed of alginate and carrageenan, was prepared using ionotropic gelation. Parameters for floatability, drug load, encapsulation efficiency, bead morphology, in vitro release, and in vivo gastric retention were evaluated. The optimized formulation via Box-Behnken design consisted of 1.7% alginate (W/V), 1.02% carrageenan (W/V), 1.4% CaCO (W/V), and a gelling bath of pH 0.8. The alginate-carrageenan-Brucea javanica oil beads had a porous structure and exhibited up to 24 h of in vitro floatability with a load capacity of 45%-55% and an encapsulation efficiency of 70%-80%. A 6-h sustained release was observed in vitro. The beads had a prolonged gastric retention (> 60% at 6 h) in fasted rats, compared to non-floating beads (15% at 6 h), as measured by gamma scintigraphy with single-photon emission tomography/computed tomography (SPET/CT). In conclusion, the alginate-carrageenan-Brucea javanica oil system showed enhanced oil encapsulation efficiency, excellent floating and gastric retention abilities, and a favorable release behavior.
Alginates
;
chemistry
;
Animals
;
Biological Availability
;
Brucea
;
chemistry
;
Carrageenan
;
chemistry
;
Delayed-Action Preparations
;
administration & dosage
;
chemistry
;
pharmacokinetics
;
Drug Carriers
;
chemistry
;
Drug Delivery Systems
;
methods
;
Drug Evaluation, Preclinical
;
Gastric Mucosa
;
metabolism
;
Glucuronic Acid
;
chemistry
;
Hexuronic Acids
;
chemistry
;
Microspheres
;
Plant Oils
;
administration & dosage
;
chemistry
;
pharmacokinetics
;
Rats
;
Rats, Sprague-Dawley
9.Improved stability and oral bioavailability of Ganneng dropping pills following transforming lignans of herpetospermum caudigerum into nanosuspensions.
Juan-Juan LI ; Ling CHENG ; Gang SHEN ; Ling QIU ; Cheng-Ying SHEN ; Juan ZHENG ; Rong XU ; Hai-Long YUAN
Chinese Journal of Natural Medicines (English Ed.) 2018;16(1):70-80
The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills (GNDP) by transforming lignans of Herpetospermum caudigerum (HL) composed of herpetrione (HPE) and herpetin (HPN) into nanosuspension (HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles (HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy (PCS), zeta potential measurement, and scanning electron microscopy (SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC, C and decrease in T when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.
Animals
;
Benzofurans
;
chemistry
;
Biological Availability
;
Cucurbitaceae
;
chemistry
;
Drug Carriers
;
chemistry
;
Drug Compounding
;
Drug Stability
;
Freeze Drying
;
Furans
;
chemistry
;
Humans
;
Lignans
;
administration & dosage
;
chemistry
;
isolation & purification
;
pharmacokinetics
;
Male
;
Nanoparticles
;
administration & dosage
;
chemistry
;
Particle Size
;
Plant Extracts
;
chemistry
;
isolation & purification
;
Rats
;
Rats, Sprague-Dawley
;
Solubility
10.Mesoporous nano-bioactive glass microspheres as a drug delivery system of minocycline.
Lin ZHU ; Yu Dong WANG ; Yan Mei DONG ; Xiao Feng CHEN
Journal of Peking University(Health Sciences) 2018;50(2):249-253
OBJECTIVE:
To construct mesoporous nano-bioactive glass (MNBG) microspheres load-release minocycline as an antibacterial drug delivery system.
METHODS:
Sol-gel method was used to synthesze MNBG microspheres as drug carrier. The MNBG consisted of SiO2, CaO, and P2O5. According to the content of silicon, MNBG microspheres were divided into four groups (60S, 70S, 80S and 90S). Scanning electron microscopy (SEM) was used to observe the surface characteristic and particle size of MNBG; Nitrogen adsorption-desorption experiment was performed to calculate the MNBG's specific surface area and the pore sizes; The Fourier transform infrared spectrum (FT-IR) and the thermogravimetric analysis were conducted to calculate the loading efficiencies of minocycline hydrochloride; UV spectrophotometric was used to determine the cumulative release of minocycline from drug-loaded particles in PBS solution within 21 d. Agar diffusion test (ADT) was performed to evaluate the antibacterial properties on Enterococcus faecalis. The inhibition zone was observed and the diameter was measured.
RESULTS:
The MNBG microspheres had good dispersion, large surface area, and even particle size. The pore sizes ranged from 4.77 nm to 7.33 nm. The loading experiment results showed that the minocycline hydrochloride loading efficiency of MNBG was related to the pore size of the microspheres. Among 60S, 70S, 80S and 90S, 60S MNBG had the highest loading efficiency of 16.33% due to its high calcium content and large pore sizes. A slow minocycline release rate from MNBG particles in PBS solution until d 21 was observed. It was showed that a burst release of 28% of the total drug for the first 24 h. A cumulative release of 35% was found, and the final concentration of minocycline maintained at about 47 mg/L. ADT showed that mino-MNBG had inhibitory effect on the growth of Enterococcus faecalis. 1 g/L minocycline, 1 g/L mino-MNBG, and 0.1 g/L minocycline presented inhibition zone, however, PBS and 1 g/L MNBG didn't. The diameter of the inhibition zone of minocycline groups was significant larger than that of mino-MNBG group (P<0.05), which was also significant larger than those of PBS and MNBG groups (P<0.05). It showed that mino-MNBG drug delivery system had antibacterial properties on Enterococcus faecalis.
CONCLUSION
The 60S MNBG that can effectively load and release minocycline may be an ideal drug carrier.
Adsorption
;
Anti-Bacterial Agents/administration & dosage*
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Drug Carriers
;
Drug Delivery Systems
;
Glass
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Microscopy, Electron, Scanning
;
Microspheres
;
Minocycline/adverse effects*
;
Nitrogen
;
Particle Size
;
Porosity
;
Silicon Dioxide
;
Spectroscopy, Fourier Transform Infrared

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