pH-Sensitive Biomaterials for Drug Delivery

Zhuo, Shijie; Zhang, Feng; Yu, Junyu; Zhang, Xican; Yang, Guangbao; Liu, Xiaowen

doi:10.3390/molecules25235649

Cited by 150 publications

(89 citation statements)

References 188 publications

(197 reference statements)

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“…These are most commonly used for triggering the release of the drug among the other stimuli. The traditionally used pH-responsive carriers show their effects based on the pH of different organs such as the intestine and stomach [ 142 ]. pH-responsive polymers can be either polyacids (which sense and release at basic pH) or polybases (which sense acidic pH and release the drug).…”

Section: Stimuli-responsive Drug Delivery Systems Using Smart Biomaterialsmentioning

confidence: 99%

Controlled Drug Delivery Systems: Current Status and Future Directions

2021

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The drug delivery system enables the release of the active pharmaceutical ingredient to achieve a desired therapeutic response. Conventional drug delivery systems (tablets, capsules, syrups, ointments, etc.) suffer from poor bioavailability and fluctuations in plasma drug level and are unable to achieve sustained release. Without an efficient delivery mechanism, the whole therapeutic process can be rendered useless. Moreover, the drug has to be delivered at a specified controlled rate and at the target site as precisely as possible to achieve maximum efficacy and safety. Controlled drug delivery systems are developed to combat the problems associated with conventional drug delivery. There has been a tremendous evolution in controlled drug delivery systems from the past two decades ranging from macro scale and nano scale to intelligent targeted delivery. The initial part of this review provides a basic understanding of drug delivery systems with an emphasis on the pharmacokinetics of the drug. It also discusses the conventional drug delivery systems and their limitations. Further, controlled drug delivery systems are discussed in detail with the design considerations, classifications and drawings. In addition, nano-drug delivery, targeted and smart drug delivery using stimuli-responsive and intelligent biomaterials is discussed with recent key findings. The paper concludes with the challenges faced and future directions in controlled drug delivery.

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Section: Stimuli-responsive Drug Delivery Systems Using Smart Biomaterialsmentioning

confidence: 99%

Controlled Drug Delivery Systems: Current Status and Future Directions

2021

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“…In a weakly acidic environment, the ester bond or amide bond can be hydrolyzed to release the connected drug. 53–55 In our study, PTX was coupled with PEG by the pH-sensitive β-carboxylic amide linkage, which could improve the hydrophilicity of PTX and could be further self-assembled to nanoparticles. Similarly, PT with metallic properties linked with LA increased load efficiency in NPs.…”

Section: Discussionmentioning

confidence: 92%

TMTP1-Modified, Tumor Microenvironment Responsive Nanoparticles Co-Deliver Cisplatin and Paclitaxel Prodrugs for Effective Cervical Cancer Therapy

Jiang

Wang

Zhou

et al. 2021

IJN

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Background and Purpose Cisplatin–paclitaxel (TP) combination chemotherapy as the first-line therapy for numerous cancers is hindered by its inadequate accumulation in tumors and severe side effects resulting from non-specific distribution. The aim of this study is to explore whether TMTP1-modified, cisplatin and paclitaxel prodrugs co-loaded nanodrug could improve cervical cancer chemotherapy and relieve its side effects through active and passive tumor targeting accumulation and controlled drug release. Methods TDNP, with capacities of active targeting for tumors and controlled drug release, was prepared to co-deliver cisplatin and paclitaxel prodrugs. The characteristics were investigated, including the diameter, surface zeta potential, stability and tumor microenvironment (TME) dependent drug release profiles. Cellular uptake, cytotoxicity, drug accumulation in tumors, antitumor effects and safety analysis were evaluated in vitro and in vivo. Results The oxidized cisplatin and the paclitaxel linked to the polymer achieved a high loading effciency of over 80% and TME-dependent sustained drug release. Moreover, TMTP1 modification enhanced cellular uptake of TDNP and further improved the cytotoxicity of TDNP in vitro. In vivo, TDNP showed an extended blood circulation and increased accumulation in SiHa xenograft models with the aid of TMTP1. More importantly, TDNP controlled tumor growth without life-threatening side effects. Conclusion Our study provided a novel TP co-delivery platform for targeted chemotherapy of cervical cancer, which was promising to improve the therapeutic effcacy of TP and may also have application in other tumors.

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“…Further experiments showed that the ACPP-DOX cellular uptake was improved after enzymatic-triggered activation, and ACPP-DOX efficiently repressed HT-1080 cell proliferation [ 165 ]. As several tumor tissues are characterized with an acidic microenvironment, drug delivery via pH-sensitive biomaterials display significant potential for responsive release of therapeutics triggered via acidic pathological tissues in tumor sites [ 166 ] ( Figure 8 ). In a related study, the ACCP CR 8 G 3 PK 6 , with a shielding group of 2,3- dimethylmaleic anhydride (DMA), was conjugated to DOX to build a novel prodrug named DOX-ACPP-DMA for tumor-targeted drug delivery [ 167 ].…”

Section: Delivery Of Chemotherapeuticsmentioning

confidence: 99%

Delivery of Various Cargos into Cancer Cells and Tissues via Cell-Penetrating Peptides: A Review of the Last Decade

et al. 2021

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Cell-penetrating peptides (CPPs), also known as protein transduction domains, are a class of diverse amino acid sequences with the ability to cross cellular membranes. CPPs can deliver several bioactive cargos, including proteins, peptides, nucleic acids and chemotherapeutics, into cells. Ever since their discovery, synthetic and natural CPPs have been utilized in therapeutics delivery, gene editing and cell imaging in fundamental research and clinical experiments. Over the years, CPPs have gained significant attention due to their low cytotoxicity and high transduction efficacy. In the last decade, multiple investigations demonstrated the potential of CPPs as carriers for the delivery of therapeutics to treat various types of cancer. Besides their remarkable efficacy owing to fast and efficient delivery, a crucial benefit of CPP-based cancer treatments is delivering anticancer agents selectively, rather than mediating toxicities toward normal tissues. To obtain a higher therapeutic index and to improve cell and tissue selectivity, CPP-cargo constructions can also be complexed with other agents such as nanocarriers and liposomes to obtain encouraging outcomes. This review summarizes various types of CPPs conjugated to anticancer cargos. Furthermore, we present a brief history of CPP utilization as delivery systems for anticancer agents in the last decade and evaluate several reports on the applications of CPPs in basic research and preclinical studies.

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pH-Sensitive Biomaterials for Drug Delivery

Cited by 150 publications

References 188 publications

Controlled Drug Delivery Systems: Current Status and Future Directions

Controlled Drug Delivery Systems: Current Status and Future Directions

TMTP1-Modified, Tumor Microenvironment Responsive Nanoparticles Co-Deliver Cisplatin and Paclitaxel Prodrugs for Effective Cervical Cancer Therapy

Delivery of Various Cargos into Cancer Cells and Tissues via Cell-Penetrating Peptides: A Review of the Last Decade

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