Integration of phospholipid-hyaluronic acid-methotrexate nanocarrier assembly and amphiphilic drug–drug conjugate for synergistic targeted delivery and combinational tumor therapy

2018 ◽  
Vol 6 (7) ◽  
pp. 1818-1833 ◽  
Author(s):  
Yang Li ◽  
Huabing Zhang ◽  
Yilin Chen ◽  
Jinyuan Ma ◽  
Jinyan Lin ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Delivery System ◽  
Targeted Delivery ◽  
Tumor Therapy ◽  
Drug Conjugate ◽  
Amphiphilic Drug ◽  
Polymeric Delivery ◽  
Dual Drug

A novel synergistic-targeting polymeric delivery system was developed to carry drug–drug conjugate for boosting dual-drug co-delivery and combinational tumor therapy.

scholarly journals Aptamer–drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity

2018 ◽  
Vol Volume 13 ◽  
pp. 763-776 ◽  
Author(s):  
Xiao-qian Dou ◽  
Hua Wang ◽  
Jing Zhang ◽  
Fang Wang ◽  
Gui-li Xu ◽  
...  
Keyword(s):  
Delivery System ◽  
Targeted Delivery ◽  
Drug Conjugate ◽  
Liposomal Delivery

scholarly journals Rational Design of Hyaluronic Acid-Based Copolymer-Mixed Micelle in Combination PD-L1 Immune Checkpoint Blockade for Enhanced Chemo-Immunotherapy of Melanoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Chaopei Zhou ◽  
Xiuxiu Dong ◽  
Chunxiang Song ◽  
Shuang Cui ◽  
Tiantian Chen ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Tumor Cells ◽  
Immune Checkpoint ◽  
Targeted Delivery ◽  
Rational Design ◽  
Mixed Micelle ◽  
Tumor Therapy ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Therapy Strategy

The application of combinational therapy breaks the limitation of monotherapy and achieves better clinical benefit for tumor therapy. Herein, a hyaluronic acid/Pluronic F68-based copolymer-mixed micelle was constructed for targeted delivery of chemotherapeutical agent docetaxel (PHDM) in combination with programmed cell death ligand-1(PD-L1) antibody. When PHDM+anti-PDL1 was injected into the blood system, PHDM could accumulate into tumor sites and target tumor cells via CD44-mediated endocytosis and possess tumor chemotherapy. While anti-PDL1 could target PD-L1 protein expressed on surface of tumor cells to the immune checkpoint blockade characteristic for tumor immunotherapy. This strategy could not only directly kill tumor cells but also improve CD8+ T cell level and facilitate effector cytokines release. In conclusion, the rational-designed PHDM+anti-PDL1 therapy strategy creates a new way for tumor immune-chemotherapy.

scholarly journals Redox/pH-Responsive 2-in-1 Chimeric Nanoparticles for the Co-Delivery of Doxorubicin and siRNA

Polymers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 4362
Author(s):  
Hsi-Chin Wu ◽  
Wei-Ting Kuo
Keyword(s):  
Hyaluronic Acid ◽  
Delivery System ◽  
Rna Silencing ◽  
Tumor Targeting ◽  
Tumor Therapy ◽  
Smart System ◽  
Chemotherapy Drugs ◽  
Dual Responsive ◽  
Interfering Rna ◽  
Structurally Stable

The co-delivery of chemotherapy drugs and gene-suppressing small interfering RNA (siRNA) show promise for cancer therapy. The key to the clinical realization of this treatment model will be the development of a carrier system enabling the simultaneous delivery (“co-delivery” instead of combinatorial delivery) of chemotherapy and siRNA agents to cancer. In this study, a co-delivery system was developed from two individual components to form one integrated nanovehicle through a redox-sensitive thiol–disulfide bond for the synergistic delivery of chemotherapy and RNA silencing: doxorubicin (Dox)-loaded N,O-carboxymethyl chitosan (NOCC) complex with a thiolated hyaluronic acid (HA-SH) nanocarrier and dopamine (Dopa)-conjugated thiolated hyaluronic acid (SH-HA-Dopa)-coated calcium phosphate (CaP)-siRNA nanocarrier. The 2-in-1 chimeric nanoparticles (NPs) were structurally stable together in the storage environment and in the circulation. This smart system selectively releases Dox and siRNA into the cytosol. Furthermore, equipped with the tumor-targeting component HA, the co-delivery system shows specific targeting and high cellular uptake efficiency by receptor-mediated endocytosis. In summary, these dual-responsive (redox and pH), tumor-targeting smart 2-in-1 chimeric NPs show promise to be employed in functional co-delivery and tumor therapy.

scholarly journals A combinational chemo-immune therapy using an enzyme-sensitive nanoplatform for dual-drug delivery to specific sites by cascade targeting

2021 ◽  
Vol 7 (6) ◽  
pp. eaba0776 ◽  
Author(s):  
Yanmei He ◽  
Lei Lei ◽  
Jun Cao ◽  
Xiaotong Yang ◽  
Shengsheng Cai ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Hyaluronic Acid ◽  
Targeted Delivery ◽  
Immune Therapy ◽  
Endosomal Escape ◽  
Shell Nanoparticles ◽  
Core Shell Nanoparticles ◽  
Mitochondria Targeting ◽  
Positively Charged ◽  
Dual Drug

Nanoparticle-based drug delivery faces challenges from the imprecise targeted delivery and the low bioavailability of drugs due to complex biological barriers. Here, we designed cascade-targeting, dual drug–loaded, core-shell nanoparticles (DLTPT) consisting of CD44-targeting hyaluronic acid shells decorated with doxorubicin (HA-DOX) and mitochondria-targeting triphenylphosphonium derivative nanoparticle cores loaded with lonidamine (LND) dimers (LTPT). DLTPT displayed prolonged blood circulation time and efficiently accumulated at the tumor site due to the tumor-homing effect and negatively charged hyaluronic acid. Subsequently, the HA-DOX shell was degraded by extracellular hyaluronidase, resulting in decreased particle size and negative-to-positive charge reversal, which would increase tumor penetration and internalization. The degradation of HA-DOX further accelerated the release of DOX and exposed the positively charged LTPT core for rapid endosomal escape and mitochondria-targeted delivery of LND. Notably, when DLTPT was used in combination with anti–PD-L1, the tumor growth was inhibited, which induced immune response against tumor metastasis.

A Smart Drug Delivery System from Charge-Conversion Polymer-Drug Conjugate for Enhancing Tumor Therapy and Tunable Drug Release

2014 ◽  
Vol 14 (4) ◽  
pp. 485-490 ◽  
Author(s):  
Hailong Huang ◽  
Yapeng Li ◽  
Zongpeng Sa ◽  
Yuan Sun ◽  
Yuzhen Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Drug Delivery System ◽  
Delivery System ◽  
Tumor Therapy ◽  
Drug Conjugate ◽  
Smart Drug ◽  
Smart Drug Delivery

scholarly journals A Hyaluronic Acid Functionalized Self-Nano-Emulsifying Drug Delivery System (SNEDDS) for Enhancement in Ciprofloxacin Targeted Delivery against Intracellular Infection

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1086
Author(s):  
Rabia Arshad ◽  
Tanveer A. Tabish ◽  
Maria Hassan Kiani ◽  
Ibrahim M. Ibrahim ◽  
Gul Shahnaz ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Hyaluronic Acid ◽  
Zeta Potential ◽  
Drug Delivery System ◽  
Droplet Size ◽  
Delivery System ◽  
Targeted Delivery ◽  
Drug Loading ◽  
Salmonella Typhi ◽  
Multi Drug Resistance

Ciprofloxacin (CIP), a potent anti-bacterial agent of the fluroquinolone family, shows poor solubility and permeability, thus leading to the development of intracellular pathogens induced multi-drug resistance and biofilms formation. To synergistically improve the biopharmaceutical parameters of CIP, a hyaluronic acid (FDA approved biocompatible polymer) functionalized self-nano emulsifying drug delivery system (HA-CIP-SNEDDS) was designed in the present study. SNEDDS formulations were tested via solubility, droplet size, zeta potential, a polydispersity index, thermodynamic stability, surface morphology, solid-state characterization, drug loading/release, cellular uptake, and biocompatibility. The final (HA-CIP-SNEDDS) formulation exhibited a mean droplet size of 50 nm with the 0.3 poly dispersity index and negative zeta potential (−11.4 mV). HA-based SNEDDS containing CIP showed an improved ability to permeate goat intestinal mucus. After 4 h, CIP-SNEDDS showed a 2-fold and HA-CIP-SNEDDS showed a 4-fold permeation enhancement as compared to the free CIP. Moreover, 80% drug release of HA-CIP-SNEDDS was demonstrated to be superior and sustained for 72 h in comparison to free CIP. However, anti-biofilm activity of HA-CIP-SNEDDS against Salmonella typhi was higher than CIP-SNEDDS and free CIP. HA-CIP-SNEDDS exhibited increased biocompatibility and improved oral pharmacokinetics as compared to free CIP. Taken together, HA-CIP-SNEDDS formulation seems to be a promising agent against Salmonella typhi with a strong targeting potential.

pH Dependent Release Potential of Natural Polymers in Sustained Release of Ornidazole From Colon Targeted Delivery System)

2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Sharma Pankaj ◽  
Tailang Mukul
Keyword(s):  
Drug Release ◽  
Delivery System ◽  
Targeted Delivery ◽  
Guar Gum ◽  
Acidic Environment ◽  
Natural Polymers ◽  
Weight Variation ◽  
Curve Determination ◽  
Preformulation Studies

The aim of present work was to prepare colon specific delivery system of Ornidazole using different ratio of shellac, zein and guar gum. From study of various literature it revealed that shellac, zein and guar gum released drug from dosage form at the pH of 6.9, 11.5, 7-9 respectively. The main problem associated with colon targeted drug delivery system is degradation of drug in the acidic environment of stomach to circumvent the present problem different combinations of shellac, zein and guar gum were employed in the formulation of colon targeted tablet. Several preformulation parameters were determined such as melting point, FTIR spectroscopy, preparation of calibration curve, determination of λmax and partition coefficient. After the preformulation studies, next steps were preparation of core tablets, evaluation of core of tablets and coating of tablets. The data obtained from preformulation study seven formulations were developed and evaluated for various parameters. Based on evaluated parameter such as weight variation, friability, dissolution study, invitro drug release etc. the F7 formulation show better results colon targeted tablets. Drug content in F7 formulation was 95% and drug release after 6 hrs was 96%. Formulation containing combination of shellac, zein and guar gum released least amount of drug in the acidic environment of stomach and released most of the drug in colon. It is evide

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