The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of...The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of non-involved tissues to cytotoxic agents.Mesenchymal stromal cells(MSC)represent a group of undifferentiated multipotent cells presenting wide self-renewal features and the capacity to differentiate into an assortment of mesenchymal family cells.During the last year,they have been proposed as natural carriers for the selective release of antitumor drugs to malignant cll,s thus optimizing cytotoxic action on cancer cll,while significantly reducing adverse side efect on healthy cells.MSC chemotherapeutic drug loading and delivery is an encouraging new area of cell therapy for several tumors,especially for those with unsatisfactory prognosis and limited treatment options available.Although some experim ental models have been sucesfuly developed,phase I dinical studies are needed to confirm this potential application of cell therapy,in particular in the case of primary and secondary lung cancers.展开更多
Drug delivery via intra-articular(IA)injection has proved to be effective in osteoarthritis(OA)therapy,limited by the drug efficiency and short retention time of the drug delivery systems(DDSs).Herein,a series of modi...Drug delivery via intra-articular(IA)injection has proved to be effective in osteoarthritis(OA)therapy,limited by the drug efficiency and short retention time of the drug delivery systems(DDSs).Herein,a series of modified cross-linked dextran(Sephadex,S0)was fabricated by respectively grafting with linear alkyl chains,branched alkyl chains or aromatic chain,and acted as DDSs after ibuprofen(Ibu)loading for OA therapy.This DDSs expressed sustained drug release,excellent anti-inflammatory and chondroprotective effects both in IL-1βinduced chondrocytes and OA joints.Specifically,the introduction of a longer hydrophobic chain,particularly an aromatic chain,distinctly improved the hydrophobicity of S0,increased Ibu loading efficiency,and further led to significantly improving OA therapeutic effects.Therefore,hydrophobic microspheres with greatly improved drug loading ratio and prolonged degradation rates show great potential to act as DDSs for OA therapy.展开更多
Low drug loading efficiency is one of the main obstacles hindering the application of contact lenses(CLs) as the carrier for extended ocular drug delivery. Here in this study, a simple and effective drug loading metho...Low drug loading efficiency is one of the main obstacles hindering the application of contact lenses(CLs) as the carrier for extended ocular drug delivery. Here in this study, a simple and effective drug loading method based on salt induced modulation was proposed and demonstrated with mechanism elucidation. First of all, using poly(2-hydroxyethyl methacrylate)(p-HEMA) as the contact lens material, betaxolol hydrochloride, Diclofenac Sodium and Betaxolol Base as the model drugs with different solubility, influence of salt concentration,salt type(sodium salts of sulfate, chloride, and sulfocyanate) and drug properties in the loading solution on drug loading efficiency was investigated. Mechanism of enhanced drug loading in contact lens was further explored via studying the influence of salt on the absorption isotherm, drug solubility and water content of CLs. Applicability of this method to other CLs materials was also investigated. It was demonstrated that adjusting the ionic strength of loading solutions resulted in significant increase of drug loading in CLs. Type and concentration of the salts and solubility of the drug were the main factors influencing enhancement ratio of drug loading. The mechanism for improved drug loading was related to the reduced drug solubility in loading solutions and the reduced bound water content in contact lenses. Modulation of drug loading by adjusting ionic strength was also applicable to other CLs and the light transmittance was not affected. This method was more suitable for salt-form drugs with high solubility. In summary, adjusting ionic strength of loading solution is an economical and effective way to improve drug loading in CLs, and this simple method may also find application in other hydrogel based drug delivery systems.展开更多
The present work explores the application of melt granulation technology to develop a high drug loaded sustained release matrix tablet of Metformin HCl using hydroxypropylcellulose(HPC) as a hydrophilic binder and ste...The present work explores the application of melt granulation technology to develop a high drug loaded sustained release matrix tablet of Metformin HCl using hydroxypropylcellulose(HPC) as a hydrophilic binder and stearic acid as an extrusion aid for producing cohesive granules. This novel approach allowed the use of a minimum number of excipients to reduce the tablet size, and to enhance compressibility of the drug. This also offered a cost effective method owing to the elimination of a ‘drying step’ prevalent in wet granulation method.Moreover, this research also focuses on resolving the processability issues associated with the use of HPC Nisso-H at high drug loading. The thermal lubricants were screened for this purpose and evaluated for their impact on extrudability, granule and tablet characteristics. Stearic acid was selected as the thermal lubricant, which not only contributed to the inhibition of burst release, but also improved the flow property of the granules.The developed matrix tablet(75% drug loading) resulted in 670 mg of weight for 500 mg dose strength and showed sustained drug release over 10 h. When compared, with conventional granulation techniques, it was observed that, under identical compression force, the tablet prepared by MG exhibited superior compactibility along with tablet hardness and optimal drug release profile. FTIR suggested nonexistence of chemical interaction between the drug and the other excipients while XRD and DSC analysis revealed the crystalline state of the drug.Furthermore, the results obtained from Raman spectroscopy proved the uniform distribution of the Metformin HCl and polymer in the final dosage form. This technology leads to the manufacture of sustained release matrix formulation with reduced tablet size of a high dose,highly water soluble drug otherwise difficult to process using standard batch-granulation.展开更多
An experimental study was carried out to investigate the amount of drugs loaded on microneedles. The microneedles were made with poly (lactic acid). Aqueous poly (vinyl alcohol) solutions were prepared as drug solutio...An experimental study was carried out to investigate the amount of drugs loaded on microneedles. The microneedles were made with poly (lactic acid). Aqueous poly (vinyl alcohol) solutions were prepared as drug solutions. Two drug loading approaches, i.e., dropping and dipping, were examined. It was found that capillary number is the only relevant dimensionless group for the two methods. For the dropping approach, dried drugs will spread near the bottom of a microneedle patch provided the surface tension is low. As for the dipping approach, both a single microneedle and an array of nine microneedles were examined. For a single microneedle, high capillary rises before pulling and pulling speed are two key factors to increase the drug loading volume. For an array of microneedles, the effect of capillary rise owing to the interaction between microneedles would increase the drug loading volume several times higher than a single microneedle of the same dimension.展开更多
Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial i...Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial infection and inflammatory reaction risks associated with foreign body exposure.Moreover,inflammation of the wound area can dramatically worsen in response to bacterial infection.These consequences can not only lead to the failure of cortical electrode implantation but also threaten the lives of patients.Herein,we prepared a hydrogel made of bacterial cellulose(BC),a flexible substrate for cortical electrodes,and further loaded antibiotic tetracycline(TC)and the anti-inflammatory drug dexamethasone(DEX)onto it.The encapsulated drugs can be released from the BC hydrogel and effectively inhibit the growth of Gram-negative and Gram-positive bacteria.Next,therapeutic cortical electrodes were developed by integrating the drug-loaded BC hydrogel and nine-channel serpentine arrays;these were used to record electrocorticography(ECoG)signals in a rat model.Due to the controlled release of TC and DEX from the BC hydrogel substrate,therapeutic cortical electrodes can alleviate or prevent symptoms associated with the bacterial infection and inflammation of brain tissue.This approach facilitates the development of drug delivery electrodes for resolving complications caused by implantable electrodes.展开更多
Lipid-based nanostructures have garnered considerable interests over the last two decades,and have achieved tremendous clinical success including thefirst clinical approval of a liposome(Doxil)for cancer therapy in 199...Lipid-based nanostructures have garnered considerable interests over the last two decades,and have achieved tremendous clinical success including thefirst clinical approval of a liposome(Doxil)for cancer therapy in 1995 and the recent COVID-19 mRNA lipid nanoparticle vaccines.Compared to liposomes which have a lipid bilayer surrounding an aqueous core,lipid nanoparticles with a particle structure have several attractive advantages for encapsulating poorly water-soluble drugs such as better stability due to the particle structure,high drug encapsulation efficiency because of a pre-or co-drug-loading strategy.While many studies have reported the synthesis of lipid nanoparticles for hydrophobic drug encapsulation,the pre-cise control of drug loading and encapsulation efficiency remains a significant challenge.This work reports a new concentration-controlled nanoprecipitation plat-form technology for fabricating lipid nanoparticles with tunable drug loading up to 70 wt%.This method is applicable for encapsulating a wide range of drugs from very hydrophobic to slightly hydrophilic.Using this facile method,nanoparticles with tunable drug loading exhibited excellent properties such as small particle size,narrow size distribution,good particle stability,showing great promise for future drug delivery applications.展开更多
Increasing drug loading remains a critical challenge in the development and translation of nanomedicine.High drug-loading nanoparticles have demonstrated unique advantages such as less carrier material used,better-con...Increasing drug loading remains a critical challenge in the development and translation of nanomedicine.High drug-loading nanoparticles have demonstrated unique advantages such as less carrier material used,better-controlled drug release,and improved efficacy and safety.Herein,we report a simple and efficient salt concentration screening method for making polymer nanoparticles with exceptionally high drug loading(up to 66.5 wt%)based on phase separation-induced nanoprecipitation.Upon addition of salt,phase separation occurs in a miscible solvent-water solution delaying the precipitation time of drugs and polymers to different extents,facilitating their co-precipitation thus the formation of high drug-loading nanoparticles with high encapsulation efficiency(>90%)and excellent stability(>1 month).This technology is versatile and easy to be adapted to various hydrophobic drugs,different polymers,and solvents.This salt-induced nanoprecipitation strategy offers a novel approach to fabricating polymer nanoparticles with tunable drug loading,and opens great potentials for future nanomedicines.展开更多
Poly(2-oxazoline)(POx)is a kind of polymeric amides that can be viewed as conformational isomers of polypeptides with excellent cyto-and hemo-compatibility,and is promising to be used as drug carriers.However,the drug...Poly(2-oxazoline)(POx)is a kind of polymeric amides that can be viewed as conformational isomers of polypeptides with excellent cyto-and hemo-compatibility,and is promising to be used as drug carriers.However,the drug loading capacity(DLC)of POx for many drugs is still low except several hydrophobic ones including paclitaxel(PTX).Herein,we prepared a series of amphiphilic POx block copolymers with various functional groups,and investigated the relationship between functional structures and the DLC.Functional POxs with benzyl,carboxyl,and amino groups in the side-chain were synthesized based on a poly(2-methyl-2-oxazoline)-block-poly(2-buty1-2-oxazoline-co-2-buteny1-2-oxazoline)(PMeOx-P(nBuOx-co-ButenOx),PMBEOx)precursor,followed by click reaction between vinyl and the 2-phenylethanethiol,thioglycolic acid and cysteamine.Using thin-film hydration method,eight commonly used drugs with various characteristics were encapsulated within these functional POx polymers.We found that amine-containing drugs were more easily encapsulated by POx with carboxyl groups,while amine functionalities in POx enhanced the loading capacity of drugs with carboxyl groups.In addition,n-n interactions resulted in enhanced DLC of most drugs,except several hydrophobic drugs with aromatic to total carbon ratios less than 0.5.In general,we could successfully encapsulate all the selected drugs with a DLC%over 10%using properly selected functional POxs.The above results confirm that the DLC of polymeric carriers can be adjusted by modifying the functional groups,and the prepared series of functional POxs provide an option for various drug loadings.展开更多
Magnetic Fe304 nanoparticles were synthesized by co-precipitation method and the mercaptopurine （MER） drug-loaded magnetic microspheres were obtained through emulsion cross-linking methods. The efficiency of this ap...Magnetic Fe304 nanoparticles were synthesized by co-precipitation method and the mercaptopurine （MER） drug-loaded magnetic microspheres were obtained through emulsion cross-linking methods. The efficiency of this approach was evaluated in terms of drug loading content （DLC）, encapsulation efficiency （EE） and delivery properties in vitro, determined by high performance liquid chromatograph （HPLC）. The microspheres showed good DLC values of 11.8%, as well as good EE values of 79.4%. The in vitro drug release study was carried out in phosphate buffer solution （PBS） simulated body fluid, at 37 ~C with pH=7.4. The release profiles showed an initial fast release rate, which decreased as time progressed and about 84 % had been released after 48 h. The experimental results indicated that the prepared magnetic microspheres may be useful for potential applications of MER for magnetically targeted chemotherapy.展开更多
Smart drug delivery nanocarriers with high drug loading capacity are of great importance in the treatment of diseases,and can improve therapeutic effectiveness as well as alleviate side effects in patients.In this wor...Smart drug delivery nanocarriers with high drug loading capacity are of great importance in the treatment of diseases,and can improve therapeutic effectiveness as well as alleviate side effects in patients.In this work,a pH and H_(2)O_(2)-responsive drug delivery platform with high doxorubicin(DOX)loading capacity has been established through coordination interaction between DOX and phenylboronic acid containing block polymer.A composited drug nanocarrier is further fabricated by growing a zeolitic imidazolate framework 8(ZIF-8)on the surface of drug-loaded polymer micelles.The study verifies that ZIF-8 shell can act as intelligent“switch”to prevent DOX leaking from core–shell nanoparticles upon H_(2)O_(2) stimulus.However,a burst drug release is detected upon pH and H_(2)O_(2) stimuli due to the further disassociation of ZIF-8 in acid solution.Moreover,the in vitro anti-cancer experiments demonstrate that the DOX-loaded core–shell nanoparticles provide effective treatment towards cancer cells but have negligible effect on normal cells,which results from the high concentration of H_(2)O_(2) and low pH in the microenvironment of tumor cells.展开更多
In the present paper, chiral mesoporous silica nano-cocoon(A-CMSN) functionalized with amino group was synthesized, and its loading and release of indomethacin(IMC), a poorly soluble drug, was studied. Due to the use ...In the present paper, chiral mesoporous silica nano-cocoon(A-CMSN) functionalized with amino group was synthesized, and its loading and release of indomethacin(IMC), a poorly soluble drug, was studied. Due to the use of chiral anionic surfactants as a template, ACMSN possessed 2D hexagonal nano-cocoon morphology with curled channels on its surface, which was quite different from another 2D hexagonal mesoporous silica nanoparticles(MCM-41) with straightway channels. After being loaded into the two silica carriers by hydrogen bond, crystalline IMC converted to amorphous form, leading to the improved drug dissolution. And IMC loading capacity of A-CMSN was higher than MCM-41 because curled loading process originating from curvature chiral channels can hold more drug molecules. Compared with IMC, IMC loaded A-CMSN presented obviously fast release throughout the in vitro release experiment, while IMC loaded MCM-41 released faster than IMC at the initial 5 h then showed controlled slow release afterwards, which was closely related to the mesoporous silica nanoparticles and different channel mesostructures of these two carriers. A-CMSN possessed nano-cocoon morphology with curled 2D hexagonal channel and its channel length was shorter than MCM-41, therefore IMC molecules can easily get rid of the constraint of A-CMSN then to be surrounded by dissolution medium.展开更多
This study was carried out to prepare ZnO nanoparticles incorporated acrylamide grafted chitosan composite film for possible biomedical application especially drug loading in wound healing. ZnO nanoparticles were prep...This study was carried out to prepare ZnO nanoparticles incorporated acrylamide grafted chitosan composite film for possible biomedical application especially drug loading in wound healing. ZnO nanoparticles were prepared by co-precipitation method from zinc acetate di-hydrate and incorporated in acrylamide grafted chitosan. FT-IR and TGA of the prepared composite film confirmed the successful incorporation of ZnO nanoparticles in the acrylamide-grafted polymer matrix. SEM images showed that the ZnO nanoparticles were homogeneously distributed on the porous matrix of the composite film. Water uptake and buffer uptake analysis revealed that the composite film could hold water and buffer sufficiently, which facilitated the absorption of exudate from the wound site. Amoxicillin was loaded in the prepared composite film and the maximum loading efficiency was found to be 67.33% with drug concentration of 300 ppm. In vitro studies showed greater antimicrobial activity of drug-loaded composite film compared to both pure film and standard antibiotic disc. Finally, the In vivo mouse model showed maximum healing efficiency compared to conventional gauge bandages because the loading of antibiotic in the film produced a synergistic effect and healing time was reduced.展开更多
The bioactive glass and related biomaterials have become increasingly popular, and have also attracted the research interest of many researchers in recent years due its special performance and tissue engineering appli...The bioactive glass and related biomaterials have become increasingly popular, and have also attracted the research interest of many researchers in recent years due its special performance and tissue engineering application. In this study, to create a material with a variety of properties Mg doped hollow bioactive glass (Mg-HBG) of 80SiO2-5P2O5-10CaO-5MgO system had been produced by using a sol-gel method. The porous structure nanoparticles were specifically made by employing the cetyltrimethylammonium bromide (CTAB) as a surfactant. Magnesium was selected as a doped material with HBG, because it is the most existing cations in the human body which helps for bone metabolism as well as it has antibacterial property. Based on different investigations resulted nanoparticle with the inclusion of the lower molar fractions magnesium has good tested result. For a drug model vancomycin hydrochloride (VAN) was used in this study and it has also good antibacterial activity effect. These findings help the possibility of using Mg-HBG nanoparticles to treat infectious bone abnormalities by demonstrating their compatibility with antibiotics, drug loading and release behavior.展开更多
文摘The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of non-involved tissues to cytotoxic agents.Mesenchymal stromal cells(MSC)represent a group of undifferentiated multipotent cells presenting wide self-renewal features and the capacity to differentiate into an assortment of mesenchymal family cells.During the last year,they have been proposed as natural carriers for the selective release of antitumor drugs to malignant cll,s thus optimizing cytotoxic action on cancer cll,while significantly reducing adverse side efect on healthy cells.MSC chemotherapeutic drug loading and delivery is an encouraging new area of cell therapy for several tumors,especially for those with unsatisfactory prognosis and limited treatment options available.Although some experim ental models have been sucesfuly developed,phase I dinical studies are needed to confirm this potential application of cell therapy,in particular in the case of primary and secondary lung cancers.
基金supported by National Natural Science Foundation of China(Grant No.82160430)Natural Science Foundation of Guangxi(Grant No.2020GXNSFAA159134 and 2019GXNSFAA185060)+1 种基金Guangxi Science and Technology Base and Talent Special Project(Grant No.GuikeAD19254003 and GuikeAD21075002)Nanning Qingxiu District Science and Technology Major Special Project(Grant No.2020013).
文摘Drug delivery via intra-articular(IA)injection has proved to be effective in osteoarthritis(OA)therapy,limited by the drug efficiency and short retention time of the drug delivery systems(DDSs).Herein,a series of modified cross-linked dextran(Sephadex,S0)was fabricated by respectively grafting with linear alkyl chains,branched alkyl chains or aromatic chain,and acted as DDSs after ibuprofen(Ibu)loading for OA therapy.This DDSs expressed sustained drug release,excellent anti-inflammatory and chondroprotective effects both in IL-1βinduced chondrocytes and OA joints.Specifically,the introduction of a longer hydrophobic chain,particularly an aromatic chain,distinctly improved the hydrophobicity of S0,increased Ibu loading efficiency,and further led to significantly improving OA therapeutic effects.Therefore,hydrophobic microspheres with greatly improved drug loading ratio and prolonged degradation rates show great potential to act as DDSs for OA therapy.
基金supported by the Distinguished Professor Project of Liaoning Province(2015)
文摘Low drug loading efficiency is one of the main obstacles hindering the application of contact lenses(CLs) as the carrier for extended ocular drug delivery. Here in this study, a simple and effective drug loading method based on salt induced modulation was proposed and demonstrated with mechanism elucidation. First of all, using poly(2-hydroxyethyl methacrylate)(p-HEMA) as the contact lens material, betaxolol hydrochloride, Diclofenac Sodium and Betaxolol Base as the model drugs with different solubility, influence of salt concentration,salt type(sodium salts of sulfate, chloride, and sulfocyanate) and drug properties in the loading solution on drug loading efficiency was investigated. Mechanism of enhanced drug loading in contact lens was further explored via studying the influence of salt on the absorption isotherm, drug solubility and water content of CLs. Applicability of this method to other CLs materials was also investigated. It was demonstrated that adjusting the ionic strength of loading solutions resulted in significant increase of drug loading in CLs. Type and concentration of the salts and solubility of the drug were the main factors influencing enhancement ratio of drug loading. The mechanism for improved drug loading was related to the reduced drug solubility in loading solutions and the reduced bound water content in contact lenses. Modulation of drug loading by adjusting ionic strength was also applicable to other CLs and the light transmittance was not affected. This method was more suitable for salt-form drugs with high solubility. In summary, adjusting ionic strength of loading solution is an economical and effective way to improve drug loading in CLs, and this simple method may also find application in other hydrogel based drug delivery systems.
基金the financial support received from University Grants Commission (UGC)
文摘The present work explores the application of melt granulation technology to develop a high drug loaded sustained release matrix tablet of Metformin HCl using hydroxypropylcellulose(HPC) as a hydrophilic binder and stearic acid as an extrusion aid for producing cohesive granules. This novel approach allowed the use of a minimum number of excipients to reduce the tablet size, and to enhance compressibility of the drug. This also offered a cost effective method owing to the elimination of a ‘drying step’ prevalent in wet granulation method.Moreover, this research also focuses on resolving the processability issues associated with the use of HPC Nisso-H at high drug loading. The thermal lubricants were screened for this purpose and evaluated for their impact on extrudability, granule and tablet characteristics. Stearic acid was selected as the thermal lubricant, which not only contributed to the inhibition of burst release, but also improved the flow property of the granules.The developed matrix tablet(75% drug loading) resulted in 670 mg of weight for 500 mg dose strength and showed sustained drug release over 10 h. When compared, with conventional granulation techniques, it was observed that, under identical compression force, the tablet prepared by MG exhibited superior compactibility along with tablet hardness and optimal drug release profile. FTIR suggested nonexistence of chemical interaction between the drug and the other excipients while XRD and DSC analysis revealed the crystalline state of the drug.Furthermore, the results obtained from Raman spectroscopy proved the uniform distribution of the Metformin HCl and polymer in the final dosage form. This technology leads to the manufacture of sustained release matrix formulation with reduced tablet size of a high dose,highly water soluble drug otherwise difficult to process using standard batch-granulation.
文摘An experimental study was carried out to investigate the amount of drugs loaded on microneedles. The microneedles were made with poly (lactic acid). Aqueous poly (vinyl alcohol) solutions were prepared as drug solutions. Two drug loading approaches, i.e., dropping and dipping, were examined. It was found that capillary number is the only relevant dimensionless group for the two methods. For the dropping approach, dried drugs will spread near the bottom of a microneedle patch provided the surface tension is low. As for the dipping approach, both a single microneedle and an array of nine microneedles were examined. For a single microneedle, high capillary rises before pulling and pulling speed are two key factors to increase the drug loading volume. For an array of microneedles, the effect of capillary rise owing to the interaction between microneedles would increase the drug loading volume several times higher than a single microneedle of the same dimension.
基金support from the National Natural Science Foundation of China(Nos.52073230,62204204,and 62288102)the Shaanxi Provincial Science Fund for Distinguished Young Scholars(No.2023-JC-JQ-32)+2 种基金the Science and Technology Innovation 2030-Major Project(No.2022ZD0208601)the Shanghai Sailing Program(No.21YF1451000)the China National Postdoctoral Program for Innovative Talents(No.BX20230494).
文摘Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial infection and inflammatory reaction risks associated with foreign body exposure.Moreover,inflammation of the wound area can dramatically worsen in response to bacterial infection.These consequences can not only lead to the failure of cortical electrode implantation but also threaten the lives of patients.Herein,we prepared a hydrogel made of bacterial cellulose(BC),a flexible substrate for cortical electrodes,and further loaded antibiotic tetracycline(TC)and the anti-inflammatory drug dexamethasone(DEX)onto it.The encapsulated drugs can be released from the BC hydrogel and effectively inhibit the growth of Gram-negative and Gram-positive bacteria.Next,therapeutic cortical electrodes were developed by integrating the drug-loaded BC hydrogel and nine-channel serpentine arrays;these were used to record electrocorticography(ECoG)signals in a rat model.Due to the controlled release of TC and DEX from the BC hydrogel substrate,therapeutic cortical electrodes can alleviate or prevent symptoms associated with the bacterial infection and inflammation of brain tissue.This approach facilitates the development of drug delivery electrodes for resolving complications caused by implantable electrodes.
基金Australian Research Council Projects,Grant/Award Number:DP200101238Australian National Health and Medical Research Council projects of Australia,Grant/Award Number:APP2008698+1 种基金Australian Research Council Discovery Early Career Researcher Award,Grant/Award Number:DE230101044Australian Government Research Training Program Scholarships。
文摘Lipid-based nanostructures have garnered considerable interests over the last two decades,and have achieved tremendous clinical success including thefirst clinical approval of a liposome(Doxil)for cancer therapy in 1995 and the recent COVID-19 mRNA lipid nanoparticle vaccines.Compared to liposomes which have a lipid bilayer surrounding an aqueous core,lipid nanoparticles with a particle structure have several attractive advantages for encapsulating poorly water-soluble drugs such as better stability due to the particle structure,high drug encapsulation efficiency because of a pre-or co-drug-loading strategy.While many studies have reported the synthesis of lipid nanoparticles for hydrophobic drug encapsulation,the pre-cise control of drug loading and encapsulation efficiency remains a significant challenge.This work reports a new concentration-controlled nanoprecipitation plat-form technology for fabricating lipid nanoparticles with tunable drug loading up to 70 wt%.This method is applicable for encapsulating a wide range of drugs from very hydrophobic to slightly hydrophilic.Using this facile method,nanoparticles with tunable drug loading exhibited excellent properties such as small particle size,narrow size distribution,good particle stability,showing great promise for future drug delivery applications.
基金Australian Research Council,Grant/Award Number:DP200101238National Health and Medical Research Council projects of Australia,Grant/Award Number:APP2008698。
文摘Increasing drug loading remains a critical challenge in the development and translation of nanomedicine.High drug-loading nanoparticles have demonstrated unique advantages such as less carrier material used,better-controlled drug release,and improved efficacy and safety.Herein,we report a simple and efficient salt concentration screening method for making polymer nanoparticles with exceptionally high drug loading(up to 66.5 wt%)based on phase separation-induced nanoprecipitation.Upon addition of salt,phase separation occurs in a miscible solvent-water solution delaying the precipitation time of drugs and polymers to different extents,facilitating their co-precipitation thus the formation of high drug-loading nanoparticles with high encapsulation efficiency(>90%)and excellent stability(>1 month).This technology is versatile and easy to be adapted to various hydrophobic drugs,different polymers,and solvents.This salt-induced nanoprecipitation strategy offers a novel approach to fabricating polymer nanoparticles with tunable drug loading,and opens great potentials for future nanomedicines.
基金the National Natural Science Foundation of China(Nos.51673185,51973215,51673189,51829302,52003268 and 52025035)as well as the support from the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2020232).
文摘Poly(2-oxazoline)(POx)is a kind of polymeric amides that can be viewed as conformational isomers of polypeptides with excellent cyto-and hemo-compatibility,and is promising to be used as drug carriers.However,the drug loading capacity(DLC)of POx for many drugs is still low except several hydrophobic ones including paclitaxel(PTX).Herein,we prepared a series of amphiphilic POx block copolymers with various functional groups,and investigated the relationship between functional structures and the DLC.Functional POxs with benzyl,carboxyl,and amino groups in the side-chain were synthesized based on a poly(2-methyl-2-oxazoline)-block-poly(2-buty1-2-oxazoline-co-2-buteny1-2-oxazoline)(PMeOx-P(nBuOx-co-ButenOx),PMBEOx)precursor,followed by click reaction between vinyl and the 2-phenylethanethiol,thioglycolic acid and cysteamine.Using thin-film hydration method,eight commonly used drugs with various characteristics were encapsulated within these functional POx polymers.We found that amine-containing drugs were more easily encapsulated by POx with carboxyl groups,while amine functionalities in POx enhanced the loading capacity of drugs with carboxyl groups.In addition,n-n interactions resulted in enhanced DLC of most drugs,except several hydrophobic drugs with aromatic to total carbon ratios less than 0.5.In general,we could successfully encapsulate all the selected drugs with a DLC%over 10%using properly selected functional POxs.The above results confirm that the DLC of polymeric carriers can be adjusted by modifying the functional groups,and the prepared series of functional POxs provide an option for various drug loadings.
基金Funded by the Natural Science Foundation of Hubei Province(No.2011CDA056)the International Cooperation Funding of Hubei Province(No.2012IHA0120)+1 种基金the Fundamental Research Funds for the Central Universities of China(2012-IV-029)the Undergraduate innovation Funding of Wuhan University of Technology(136620004)
文摘Magnetic Fe304 nanoparticles were synthesized by co-precipitation method and the mercaptopurine （MER） drug-loaded magnetic microspheres were obtained through emulsion cross-linking methods. The efficiency of this approach was evaluated in terms of drug loading content （DLC）, encapsulation efficiency （EE） and delivery properties in vitro, determined by high performance liquid chromatograph （HPLC）. The microspheres showed good DLC values of 11.8%, as well as good EE values of 79.4%. The in vitro drug release study was carried out in phosphate buffer solution （PBS） simulated body fluid, at 37 ~C with pH=7.4. The release profiles showed an initial fast release rate, which decreased as time progressed and about 84 % had been released after 48 h. The experimental results indicated that the prepared magnetic microspheres may be useful for potential applications of MER for magnetically targeted chemotherapy.
基金financially supported by the Natural Science Foundation of Zhejiang Province(No.LY20E030005)。
文摘Smart drug delivery nanocarriers with high drug loading capacity are of great importance in the treatment of diseases,and can improve therapeutic effectiveness as well as alleviate side effects in patients.In this work,a pH and H_(2)O_(2)-responsive drug delivery platform with high doxorubicin(DOX)loading capacity has been established through coordination interaction between DOX and phenylboronic acid containing block polymer.A composited drug nanocarrier is further fabricated by growing a zeolitic imidazolate framework 8(ZIF-8)on the surface of drug-loaded polymer micelles.The study verifies that ZIF-8 shell can act as intelligent“switch”to prevent DOX leaking from core–shell nanoparticles upon H_(2)O_(2) stimulus.However,a burst drug release is detected upon pH and H_(2)O_(2) stimuli due to the further disassociation of ZIF-8 in acid solution.Moreover,the in vitro anti-cancer experiments demonstrate that the DOX-loaded core–shell nanoparticles provide effective treatment towards cancer cells but have negligible effect on normal cells,which results from the high concentration of H_(2)O_(2) and low pH in the microenvironment of tumor cells.
基金supported by Postdoctoral Science Foundation of China 2017M611268
文摘In the present paper, chiral mesoporous silica nano-cocoon(A-CMSN) functionalized with amino group was synthesized, and its loading and release of indomethacin(IMC), a poorly soluble drug, was studied. Due to the use of chiral anionic surfactants as a template, ACMSN possessed 2D hexagonal nano-cocoon morphology with curled channels on its surface, which was quite different from another 2D hexagonal mesoporous silica nanoparticles(MCM-41) with straightway channels. After being loaded into the two silica carriers by hydrogen bond, crystalline IMC converted to amorphous form, leading to the improved drug dissolution. And IMC loading capacity of A-CMSN was higher than MCM-41 because curled loading process originating from curvature chiral channels can hold more drug molecules. Compared with IMC, IMC loaded A-CMSN presented obviously fast release throughout the in vitro release experiment, while IMC loaded MCM-41 released faster than IMC at the initial 5 h then showed controlled slow release afterwards, which was closely related to the mesoporous silica nanoparticles and different channel mesostructures of these two carriers. A-CMSN possessed nano-cocoon morphology with curled 2D hexagonal channel and its channel length was shorter than MCM-41, therefore IMC molecules can easily get rid of the constraint of A-CMSN then to be surrounded by dissolution medium.
文摘This study was carried out to prepare ZnO nanoparticles incorporated acrylamide grafted chitosan composite film for possible biomedical application especially drug loading in wound healing. ZnO nanoparticles were prepared by co-precipitation method from zinc acetate di-hydrate and incorporated in acrylamide grafted chitosan. FT-IR and TGA of the prepared composite film confirmed the successful incorporation of ZnO nanoparticles in the acrylamide-grafted polymer matrix. SEM images showed that the ZnO nanoparticles were homogeneously distributed on the porous matrix of the composite film. Water uptake and buffer uptake analysis revealed that the composite film could hold water and buffer sufficiently, which facilitated the absorption of exudate from the wound site. Amoxicillin was loaded in the prepared composite film and the maximum loading efficiency was found to be 67.33% with drug concentration of 300 ppm. In vitro studies showed greater antimicrobial activity of drug-loaded composite film compared to both pure film and standard antibiotic disc. Finally, the In vivo mouse model showed maximum healing efficiency compared to conventional gauge bandages because the loading of antibiotic in the film produced a synergistic effect and healing time was reduced.
文摘The bioactive glass and related biomaterials have become increasingly popular, and have also attracted the research interest of many researchers in recent years due its special performance and tissue engineering application. In this study, to create a material with a variety of properties Mg doped hollow bioactive glass (Mg-HBG) of 80SiO2-5P2O5-10CaO-5MgO system had been produced by using a sol-gel method. The porous structure nanoparticles were specifically made by employing the cetyltrimethylammonium bromide (CTAB) as a surfactant. Magnesium was selected as a doped material with HBG, because it is the most existing cations in the human body which helps for bone metabolism as well as it has antibacterial property. Based on different investigations resulted nanoparticle with the inclusion of the lower molar fractions magnesium has good tested result. For a drug model vancomycin hydrochloride (VAN) was used in this study and it has also good antibacterial activity effect. These findings help the possibility of using Mg-HBG nanoparticles to treat infectious bone abnormalities by demonstrating their compatibility with antibiotics, drug loading and release behavior.
