Biological assessment of self-assembled polymeric micelles for pulmonary administration of insulin

Andrade, Fernanda; Neves, José das; Gener, Petra; Schwartz, Simó; Ferreira, Domingos; Oliva, Mireia

doi:10.1016/j.nano.2015.05.006

Cited by 42 publications

(16 citation statements)

References 64 publications

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“…Different Pluronic ® (F68, F108, F127) were tested, being the Pluronic ® F127 selected due to its better technological features ( Figure 1(A) ). The smaller size and Pdi of F127-based micelles can be explained by its lower CMC, hydrophilic-lipophilic balance (HLB) and CMT (24 °C for 1% w/v (Andrade et al., 2015b ; Andrade et al., 2015a )), whereas F68 presents the higher CMC and CMT (54–56.21 °C for 1% w/v (Lin & Alexandridis, 2002 )) and consequently higher diameter. The same behavior was observed previously (Tsui et al., 2010 ).…”

Section: Discussionmentioning

confidence: 99%

AKT2 siRNA delivery with amphiphilic-based polymeric micelles show efficacy against cancer stem cells

et al. 2018

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Development of RNA interference-based therapies with appropriate therapeutic window remains a challenge for advanced cancers. Because cancer stem cells (CSC) are responsible of sustaining the metastatic spread of the disease to distal organs and the progressive gain of resistance of advanced cancers, new anticancer therapies should be validated specifically for this subpopulation of cells. A new amphihilic-based gene delivery system that combines Pluronic® F127 micelles with polyplexes spontaneously formed by electrostatic interaction between anionic siRNA and cationic polyethylenimine (PEI) 10K, was designed (PM). Resultant PM gather the requirements for an efficient and safe transport of siRNA in terms of its physicochemical characteristics, internalization capacity, toxicity profile and silencing efficacy. PM were loaded with a siRNA against AKT2, an important oncogene involved in breast cancer tumorigenesis, with a special role in CSC malignancy. Efficacy of siAKT2-PM was validated in CSC isolated from two breast cancer cell lines: MCF-7 and Triple Negative MDA-MB-231 corresponding to an aggressive subtype of breast cancer. In both cases, we observed significant reduction on cell invasion capacity and strong inhibition of mammosphere formation after treatment. These results prompt AKT2 inhibition as a powerful therapeutic target against CSC and pave the way to the appearance of more effective nanomedicine-based gene therapies aimed to prevent CSC-related tumor recurrence.

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Section: Discussionmentioning

confidence: 99%

AKT2 siRNA delivery with amphiphilic-based polymeric micelles show efficacy against cancer stem cells

et al. 2018

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“…Polymeric micelles have been investigated as alternative vehicles for parenteral,[ 47 ] oral,[ 23 ] ocular,[ 48 ] pulmonary,[ 49 ] and nasal routes. [ 50 ] However, investigation to targeted cutaneous delivery by application of polymeric micelles is rare, and the mechanism of their action is not clearly demonstrated.…”

Section: Polymeric Micelles In Skin Drug Deliverymentioning

confidence: 99%

Polymeric micelles as cutaneous drug delivery system in normal skin and dermatological disorders

Makhmalzade

Chavoshy

2018

J Adv Pharm Technol Res

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The easy accessibility of skin made dermal application, one of the approaches for local drug therapy. Effectiveness of topical drug application is depended on different parameters such as skin barrier properties, physicochemical properties of drug and vehicle, and interaction between drug and its vehicle with the skin layers. In this review, an overview of skin structure and feature of polymeric micelles as topical nanocarriers is provided. We also summarized the research studies dealing with the application of polymeric micelles for cutaneous delivery. In the past decades, numerous types of nanocarriers have been widely investigated as a novel delivery approach to improve skin penetration and localization of drugs in normal skin and dermatological diseases. Polymeric micelles are one of them, with their specific ability to encapsulate hydrophilic drugs. These carriers can enhance the therapeutic efficacy and minimize the systemic side effects of the drugs. Polymeric micelles could enhance the deposition of drugs in targeted sites of the skin in the normal and dermatological diseases such as psoriasis and acne. Nevertheless, still there is a need to investigate the mechanism of action of these carriers and the fate of polymeric micelles in skin.

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“…Because of its small size, biocompatibility, stealth properties and amphiphilic nature, this is an ideal system to overcome major drawbacks related to intracellular delivery of antibodies. Furthermore, poloxamer polymers like Pluronic ® F127 have shown to interfere with the function of P-glycoprotein, being therefore helpful to further overcome drug resistance and reduce cancer recurrence [22][23][24]. Moreover, taking advantage of the plasticity provided by amphiphilic PM we have also explored potential combinatorial therapeutic strategies with 5-FU and PTX, drugs commonly used in colon and breast cancer, respectively.…”

Section: Introductionmentioning

confidence: 99%

Intracellular Delivery of Anti-SMC2 Antibodies against Cancer Stem Cells

et al. 2020

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Structural maintenance of chromosomes protein 2 (SMC2) is a central component of the condensin complex involved in DNA supercoiling, an essential process for embryonic stem cell survival. SMC2 over-expression has been related with tumorigenesis and cancer malignancy and its inhibition is regarded as a potential therapeutic strategy even though no drugs are currently available. Here, we propose to inhibit SMC2 by intracellular delivery of specific antibodies against the SMC2 protein. This strategy aims to reduce cancer malignancy by targeting cancer stem cells (CSC), the tumoral subpopulation responsible of tumor recurrence and metastasis. In order to prevent degradation and improve cellular internalization, anti-SMC2 antibodies (Ab-SMC2) were delivered by polymeric micelles (PM) based on Pluronic® F127 amphiphilic polymers. Importantly, scaffolding the Ab-SMC2 onto nanoparticles allowed its cellular internalization and highly increased its efficacy in terms of cytotoxicity and inhibition of tumorsphere formation in MDA-MB-231 and HCT116 breast and colon cancer cell lines, respectively. Moreover, in the case of the HCT116 cell line G1, cell-cycle arrest was also observed. In contrast, no effects from free Ab-SMC2 were detected in any case. Further, combination therapy of anti-SMC2 micelles with paclitaxel (PTX) and 5-Fluorouracil (5-FU) was also explored. For this, PTX and 5-FU were respectively loaded into an anti-SMC2 decorated PM. The efficacy of both encapsulated drugs was higher than their free forms in both the HCT116 and MDA-MB-231 cell lines. Remarkably, micelles loaded with Ab-SMC2 and PTX showed the highest efficacy in terms of inhibition of tumorsphere formation in HCT116 cells. Accordingly, our data clearly suggest an effective intracellular release of antibodies targeting SMC2 in these cell models and, further, strong cytotoxicity against CSC, alone and in combined treatments with Standard-of-Care drugs.

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Biological assessment of self-assembled polymeric micelles for pulmonary administration of insulin

Cited by 42 publications

References 64 publications

AKT2 siRNA delivery with amphiphilic-based polymeric micelles show efficacy against cancer stem cells

AKT2 siRNA delivery with amphiphilic-based polymeric micelles show efficacy against cancer stem cells

Polymeric micelles as cutaneous drug delivery system in normal skin and dermatological disorders

Intracellular Delivery of Anti-SMC2 Antibodies against Cancer Stem Cells

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