Bioinspired and biomimetic systems for advanced drug and gene delivery

Sabu, Chinnu; Rejo, Christine; Kotta, Sabna; Pramod, K.

doi:10.1016/j.jconrel.2018.08.033

Cited by 96 publications

(58 citation statements)

References 120 publications

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“…carriers. 54,55 Another approach involves common modifications with specific ligands to protein receptors expressed on the surface of the cancer cells, typically folic acid ligands 56 or the tumor-homing and tumor-penetrating cyclic iRGD peptide, also due to its ability to increases the tumor vascular permeability. 57,58 Of course, the anti-cancer efficacy of the GMO-AT101 formulation requires further investigation in the GBM model in vivo.…”

Section: Encapsulated At101 Exhibits Stronger Cytotoxic Effects and Mmentioning

confidence: 99%

<p>AT101-Loaded Cubosomes as an Alternative for Improved Glioblastoma Therapy</p>

Flak

Adamski

Nowaczyk

et al. 2020

IJN

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Introduction: AT101, the R-(-)-enantiomer of the cottonseed-derived polyphenol gossypol, is a promising drug in glioblastoma multiforme (GBM) therapy due to its ability to trigger autophagic cell death but also to facilitate apoptosis in tumor cells. It does have some limitations such as poor solubility in water-based media and consequent low bioavailability, which affect its response rate during treatment. To overcome this drawback and to improve the anti-cancer potential of AT101, the use of cubosome-based formulation for AT101 drug delivery has been proposed. This is the first report on the use of cubosomes as AT101 drug carriers in GBM cells. Materials and Methods: Cubosomes loaded with AT101 were prepared from glyceryl monooleate (GMO) and the surfactant Pluronic F-127 using the top-down approach. The drug was introduced into the lipid prior to dispersion. Prepared formulations were then subjected to complex physicochemical and biological characterization. Results: Formulations of AT101-loaded cubosomes were highly stable colloids with a high drug entrapment efficiency (97.7%) and a continuous, sustained drug release approaching 35% over 72 h. Using selective and sensitive NMR diffusometry, the drug was shown to be efficiently bound to the lipid-based cubosomes. In vitro imaging studies showed the high efficiency of cubosomal nanoparticles uptake into GBM cells, as well as their marked ability to penetrate into tumor spheroids. Treatment of GBM cells with the AT101-loaded cubosomes, but not with the free drug, induced cytoskeletal rearrangement and shortening of actin fibers. The prepared nanoparticles revealed stronger in vitro cytotoxic effects against GBM cells (A172 and LN229 cell lines), than against normal brain cells (SVGA and HMC3 cell lines). Conclusion: The results indicate that GMO-AT101 cubosome formulations are a promising basic tool for alternative approaches to GBM treatment.

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Section: Encapsulated At101 Exhibits Stronger Cytotoxic Effects and Mmentioning

confidence: 99%

<p>AT101-Loaded Cubosomes as an Alternative for Improved Glioblastoma Therapy</p>

Flak

Adamski

Nowaczyk

et al. 2020

IJN

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“…Several types of virus, including retrovirus, adenovirus, adeno-associated virus, and herpes simplex virus, have been explored [12,13]. Inspired by these viruses, various drug delivery systems, such as virus-like particles and virosomes have been proposed [11,14]. However, over the years, the use of these vectors has revealed some drawbacks, such as their difficult and expensive production in large quantities and the presence of residual viral elements that can potentially cause an inflammatory response, cytotoxicity, immunogenicity and insertional mutagenesis [12,14].…”

Section: Viral Delivery Systemsmentioning

confidence: 99%

“…Thus, several efforts are being made to overcome these shortcomings. For further reading on virus-inspired nanocarriers for drug delivery, please refer to the review by Sabu et al [14].…”

Section: Viral Delivery Systemsmentioning

confidence: 99%

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

et al. 2020

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Central nervous system (CNS) disorders encompass a vast spectrum of pathological conditions and represent a growing concern worldwide. Despite the high social and clinical interest in trying to solve these pathologies, there are many challenges to bridge in order to achieve an effective therapy. One of the main obstacles to advancements in this field that has hampered many of the therapeutic strategies proposed to date is the presence of the CNS barriers that restrict the access to the brain. However, adequate brain biodistribution and neuronal cells specific accumulation in the targeted site also represent major hurdles to the attainment of a successful CNS treatment. Over the last few years, nanotechnology has taken a step forward towards the development of therapeutics in neurologic diseases and different approaches have been developed to surpass these obstacles. The versatility of the designed nanocarriers in terms of physical and chemical properties, and the possibility to functionalize them with specific moieties, have resulted in improved neurotargeted delivery profiles. With the concomitant progress in biology research, many of these strategies have been inspired by nature and have taken advantage of physiological processes to achieve brain delivery. Here, the different nanosystems and targeting moieties used to achieve a neuronal delivery reported in the open literature are comprehensively reviewed and critically discussed, with emphasis on the most recent bioinspired advances in the field. Finally, we express our view on the paramount challenges in targeted neuronal delivery that need to be overcome for these promising therapeutics to move from the bench to the bedside.

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“…Recently, there has been a focus on finding effective transporter vehicles for drugs. These systems, known as drug delivery systems (DDS), are characterized by properties that improve the biocompatibility, biodistribution, and physicochemical properties of a medicine once it has been administered [ 1 ]. One of the most difficult challenges associated with the design of new DDS is that they should not interact with the immune system [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Human Serum Albumin Binds Native Insulin and Aggregable Insulin Fragments and Inhibits Their Aggregation

et al. 2020

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The purpose of this study was to investigate whether Human Serum Albumin (HSA) can bind native human insulin and its A13–A19 and B12–B17 fragments, which are responsible for the aggregation of the whole hormone. To label the hormone and both hot spots, so that their binding positions within the HSA could be identified, 4-(1-pyrenyl)butyric acid was used as a fluorophore. Triazine coupling reagent was used to attach the 4-(1-pyrenyl)butyric acid to the N-terminus of the peptides. When attached to the peptides, the fluorophore showed extended fluorescence lifetimes in the excited state in the presence of HSA, compared to the samples in buffer solution. We also analyzed the interactions of unlabeled native insulin and its hot spots with HSA, using circular dichroism (CD), the microscale thermophoresis technique (MST), and three independent methods recommended for aggregating peptides. The CD spectra indicated increased amounts of the α-helical secondary structure in all analyzed samples after incubation. Moreover, for each of the two unlabeled hot spots, it was possible to determine the dissociation constant in the presence of HSA, as 14.4 µM (A13–A19) and 246 nM (B12–B17). Congo Red, Thioflavin T, and microscopy assays revealed significant differences between typical amyloids formed by the native hormone or its hot-spots and the secondary structures formed by the complexes of HSA with insulin and A13–A19 and B12–B17 fragments. All results show that the tested peptide-probe conjugates and their unlabeled analogues interact with HSA, which inhibits their aggregation.

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Bioinspired and biomimetic systems for advanced drug and gene delivery

Cited by 96 publications

References 120 publications

<p>AT101-Loaded Cubosomes as an Alternative for Improved Glioblastoma Therapy</p>

<p>AT101-Loaded Cubosomes as an Alternative for Improved Glioblastoma Therapy</p>

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

Human Serum Albumin Binds Native Insulin and Aggregable Insulin Fragments and Inhibits Their Aggregation

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