Lipid polymer hybrid nanocarriers: Insights into synthesis aspects, characterization, release mechanisms, surface functionalization and potential implications

Shah, Saurabh; Famta, Paras; Raghuvanshi, Rajeev Singh; Singh, Shashi Bala; Srivastava, Saurabh

doi:10.1016/j.colcom.2021.100570

Cited by 53 publications

(23 citation statements)

References 126 publications

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“…However, lipid-based nanosystems usually have the drawback of limited stability, 32 whereas polymers are plagued with poor drug loading and dispersed molecular weight distribution. 33 , 34 An ideal nanosystems-based delivery system is expected to harbor the advantageous features of both lipid and polymer vectors while overcoming their pitfalls. It has been reported that nanosystems formed by amphiphilic dendrimers are able to combine the self-assembling feature of lipids and the stability of dendrimeric polymers.…”

Section: Resultsmentioning

confidence: 99%

Amphiphilic Dendritic Nanomicelle-Mediated Delivery of Gemcitabine for Enhancing the Specificity and Effectiveness

Zhao¹,

Yang²,

Li³

et al. 2022

IJN

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Gemcitabine is the first line and the gold standard drug for pancreatic cancer. However, the anticancer efficacy is severely limited by its instability and poor cellular uptake. To enhance the clinical efficacy of gemcitabine, we constructed a novel nanodrug delivery system based on amphiphilic dendrimers and aliphatic gemcitabine prodrug. Methods: An aliphatic gemcitabine prodrug and a small amphiphilic dendrimer were synthesized and characterized by high resolution mass spectrometry (HRMS) as well as nuclear magnetic resonance (NMR). Then the aliphatic gemcitabine prodrug was encapsulated into the small amphiphilic dendrimer by film dispersion method, resulting in a novel nanodrug delivery system. Subsequently, the size, morphology, drug loading, stability, drug release profiles, cell uptake, toxicity, the anticancer activity and in vivo distribution of the new developed gemcitabine delivery system were systematically evaluated by different technical methods, including transmission electron microscopy (TEM), dynamic light-scattering (DLS), ultraviolet spectrophotometer, flow cytometry, in vivo imaging system etc. Results: We developed a novel nanodrug delivery system of gemcitabine using amphiphilic dendrimer. This dendrimer-based gemcitabine nanoformulation reported here possess a high drug loading of 33%. With the features of small size, stable formulation and pH-responsive drug release, the obtained gemcitabine nanoformulation could effectively accumulate in tumor site and rapid uptake in cells. Finally, the gemcitabine nanoformulation displayed more potent anticancer activity compared to free gemcitabine both in vitro and in vivo. Moreover, the nanodrug displayed greatly reduced adverse effects and satisfactory biocompatibility. Conclusion: Benefiting the advantageous features of both amphiphilic dendrimers and nanotechnology-based drug delivery, this gemcitabine nanosystem constitutes a promising therapeutic candidate for pancreatic cancer treatment. This study also underlines the potential use of self-assembling amphiphilic dendrimer-based nanotechnology for improving drug efficacy as well as reducing drug toxicity.

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Section: Resultsmentioning

confidence: 99%

Amphiphilic Dendritic Nanomicelle-Mediated Delivery of Gemcitabine for Enhancing the Specificity and Effectiveness

Zhao¹,

Yang²,

Li³

et al. 2022

IJN

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“…Lipid–polymer assembling is a remarkable combination of organic matrices resulting in hybrid DDS with extraordinary properties and complex supramolecular arrangements [ 35 , 36 , 37 ]. In here, the first step in the development of the lipid–biopolymer nanobead consisted in the CHT/NLC-INDO preparation.…”

Section: Discussionmentioning

confidence: 99%

Hybrid Nanobeads for Oral Indomethacin Delivery

et al. 2022

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The oral administration of the anti-inflammatory indomethacin (INDO) causes severe gastrointestinal side effects, which are intensified in chronic inflammatory conditions when a continuous treatment is mandatory. The development of hybrid delivery systems associates the benefits of different (nano) carriers in a single system, designed to improve the efficacy and/or minimize the toxicity of drugs. This work describes the preparation of hybrid nanobeads composed of nanostructured lipid carriers (NLC) loading INDO (2%; w/v) and chitosan, coated by xanthan. NLC formulations were monitored in a long-term stability study (25 °C). After one year, they showed suitable physicochemical properties (size < 250 nm, polydispersity < 0.2, zeta potential of −30 mV and spherical morphology) and an INDO encapsulation efficiency of 99%. The hybrid (lipid-biopolymers) nanobeads exhibited excellent compatibility between the biomaterials, as revealed by structural and thermodynamic properties, monodisperse size distribution, desirable in vitro water uptake and prolonged in vitro INDO release (26 h). The in vivo safety of hybrid nanobeads was confirmed by the chicken embryo (CE) toxicity test, considering the embryos viability, weights of CE and annexes and changes in the biochemical markers. The results point out a safe gastro-resistant pharmaceutical form for further efficacy assays.

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“…Given the high lipophilicity of TMZ, the researchers suggested that NLCs would be a more acceptable system for transporting the drug due to its expected greater solubility in the liquid core. The described advantages made it possible to significantly increase the amount of substance encapsulated by NLC transporters [ 66 , 70 ]. According to experimental data, temozolomide contained in solid lipid nanoparticles (TMZ-SLN) is less effective than that enclosed in the structure of nanolipid carriers (TMZ-NLC) [ 71 , 72 ].…”

Section: Nanoscale Delivery Systemsmentioning

confidence: 99%

Temozolomide Efficacy and Metabolism: The Implicit Relevance of Nanoscale Delivery Systems

et al. 2022

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The most common primary malignant brain tumors in adults are gliomas. Glioblastoma is the most prevalent and aggressive tumor subtype of glioma. Current standards for the treatment of glioblastoma include a combination of surgical, radiation, and drug therapy methods. The drug therapy currently includes temozolomide (TMZ), an alkylating agent, and bevacizumab, a recombinant monoclonal IgG1 antibody that selectively binds to and inhibits the biological activity of vascular endothelial growth factor. Supplementation of glioblastoma radiation therapy with TMZ increased patient survival from 12.1 to 14.6 months. The specificity of TMZ effect on brain tumors is largely determined by special aspects of its pharmacokinetics. TMZ is an orally bioavailable prodrug, which is well absorbed from the gastrointestinal tract and is converted to its active alkylating metabolite 5-(3-methyl triazen-1-yl)imidazole-4-carbozamide (MTIC) spontaneously in physiological condition that does not require hepatic involvement. MTIC produced in the plasma is not able to cross the BBB and is formed locally in the brain. A promising way to increase the effectiveness of TMZ chemotherapy for glioblastoma is to prevent its hydrolysis in peripheral tissues and thereby increase the drug concentration in the brain that nanoscale delivery systems can provide. The review discusses possible ways to increase the efficacy of TMZ using nanocarriers.

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Lipid polymer hybrid nanocarriers: Insights into synthesis aspects, characterization, release mechanisms, surface functionalization and potential implications

Cited by 53 publications

References 126 publications

Amphiphilic Dendritic Nanomicelle-Mediated Delivery of Gemcitabine for Enhancing the Specificity and Effectiveness

Amphiphilic Dendritic Nanomicelle-Mediated Delivery of Gemcitabine for Enhancing the Specificity and Effectiveness

Hybrid Nanobeads for Oral Indomethacin Delivery

Temozolomide Efficacy and Metabolism: The Implicit Relevance of Nanoscale Delivery Systems

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