Intracellular Drug Delivery by Genetically Engineered High-Density Lipoprotein Nanoparticles

Murakami, Tatsuya; Wijagkanalan, Wassana; Hashida, Mitsuru; Tsuchida, Kunihiro

doi:10.2217/nnm.10.66

Cited by 45 publications

(50 citation statements)

References 33 publications

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“…The carriers used are recombinant, formed by suspending triglycerides with bacterially expressed Apolipoprotein A1 (Apo-A1) followed by heating and sonication [83]. The advent of Apo-A1 fusion proteins delineated two possibilities; the fusion protein could be therapeutic or, since the Apo-A1 sits at the interface, the fusion protein could include a targeting peptide [84]. In one instance, interleukin-11α was selected as a targeting peptide as the receptor is highly expressed in various cancer cell lines [85,86].…”

Section: Lipoproteins As Carriersmentioning

confidence: 99%

“…These particles showed selective targeting to osteosarcoma masses and the addition of a cytotoxic peptide demonstrated efficacy in vitro . Efficacy was also demonstrated in mice by fusing the cell penetrating TAT peptide from the human immunodeficiency virus to Apo-A1 carrying unmodified doxorubicin in the particle and administering intravenously [84]. The particles release about 40% of the encapsulated doxorubicin within 5 h in normal saline containing 0.1% bovine serum albumin.…”

Section: Lipoproteins As Carriersmentioning

confidence: 99%

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Fatty acids as therapeutic auxiliaries for oral and parenteral formulations

Hackett

Zaro

Shen

et al. 2013

Advanced Drug Delivery Reviews

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Many drugs have decreased therapeutic activity due to issues with absorption, distribution, metabolism and excretion. The co-formulation or covalent attachment of drugs with fatty acids has demonstrated some capacity to overcome these issues by improving intestinal permeability, slowing clearance and binding serum proteins for selective tissue uptake and metabolism. For orally administered drugs, albeit at low level of availability, the presence of fatty acids and triglycerides in the intestinal lumen may promote intestinal uptake of small hydrophilic molecules. Small lipophilic drugs or acylated hydrophilic drugs also show increased lymphatic uptake and enhanced passive diffusional uptake. Fatty acid conjugation of small and large proteins or peptides have exhibited protracted plasma half-lives, site-specific delivery and sustained release upon parenteral administration. These improvements are most likely due to associations with lipid-binding serum proteins, namely albumin, LDL and HDL. These molecular interactions, although not fully characterized, could provide the ability of using the endogenous carrier systems for improving therapeutic outcomes.

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Section: Lipoproteins As Carriersmentioning

confidence: 99%

Section: Lipoproteins As Carriersmentioning

confidence: 99%

Fatty acids as therapeutic auxiliaries for oral and parenteral formulations

Hackett

Zaro

Shen

et al. 2013

Advanced Drug Delivery Reviews

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show abstract

“…30 Briefly, the PC-3, SKOV-3, PZ-HPV, and HiO180 were grown according to procedures and culturing conditions provided by the ATCC in their respective media as stated earlier in 75 cm 2 flasks and incubated at 37°C and 5% CO 2.…”

Section: Determination Of Ic 50 Dosesmentioning

confidence: 99%

Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles

Sabnis¹,

Nair²,

Israel³

et al. 2012

IJN

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Among numerous drug-delivery approaches, reconstituted high-density lipoprotein (rHDL) nanocarriers have proven particularly applicable for delivering highly hydrophobic drugs. In this study, we have investigated the enhancement of the therapeutic impact of valrubicin (AD-32), an antineoplastic agent that has been limited to intravesicular application against bladder cancer, despite the encouraging original preclinical data. Earlier studies validated the superior therapeutic efficacy of AD-32 over doxorubicin. In the present study, rHDL/AD-32 nanoparticles were formulated and characterized with regard to encapsulation efficiency, physicochemical properties, selective toxicity, and receptor-mediated uptake. The half maximal inhibitory concentration values (IC 50 ) for rHDL/AD-32 nanoparticles were 1.8 and 2.6 times lower than the free AD-32 for prostate (PC-3) and ovarian (SKOV-3) cancer cell lines, respectively, whereas nonmalignant cell lines demonstrated 5 and 1.48 times higher IC 50 doses with rHDL/AD-32 formulations. The data obtained demonstrated effective receptor-mediated uptake of AD-32 from the rHDL nanocarriers by PC-3 and SKOV-3 cancer cells via a targeted drug-delivery process. The rHDL/AD-32 formulation was stable for 6 months when stored at 4°C or at -20°C, as 92% of the AD-32 was retained in the nanoparticles. The findings from this study show that the rHDL/AD-32 formulation can overcome the solubility barriers of AD-32 and thus serve as an effective systemically administered chemotherapeutic agent.

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“…Additionally, lipid core of these particles is suitable for drug loading (Figure a) and most importantly, because of innate receptor‐dependence of HDLs function, it is possible to direct these particles to different tissues and organs through the addition of various ligands on them (Figure a). Also, adding of specific ligands into the complex may result in the efficient and specific transferring of drugs into the cancer cells, thus leading to suppression of tumor growth . On the other hand, by manipulating the content of different lipids and apolipoproteins, it is possible to change the physicochemical properties of synthetic HDLs that can affect the stability of these particles, the amounts of loaded drugs and their therapeutic efficacy …”

Section: High‐density Lipoproteins and Targeted Drug Delivery In Cancermentioning

confidence: 99%

“…Finally, it has been observed that using of HDLs/DXR complex in addition to the sustained release of DXR led to enhanced intracellular DXR delivery into the MDA‐MB‐231 (human breast cancer cells) and NCI‐H460 (human non‐small‐cell lung cancer). However, adding of TAT into the complex resulted in the transferring of DXR from endosome to nucleus that led to more efficiently suppression of tumor growth than HDLs/DXR complex in mice …”

Section: Application Of Hdls In Passive Drug Deliverymentioning

confidence: 99%

The role of high‐density lipoproteins in antitumor drug delivery

et al. 2019

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High‐density lipoproteins (HDLs) are the smallest lipoprotein with the highest level of protein in their surface. The main role of HDLs are reverse transport of cholesterol from peripheral tissues to the liver. More recently, HDLs have been considered as a new drug delivery system because of their small size, proper surface properties, long circulation time, biocompatibility, biodegradability, and low immune stimulation. Delivery of anticancer drug to the tumor tissue is a major obstacle against successful chemotherapy, which is because of the toxicity and poor aqueous solubility of these drugs. Loading chemotherapeutic drugs in the lipid core of HDLs can overcome the aforementioned problems and increase the efficiency of drug delivery. In this review, we discuss the use of HDLs particles in drug delivery to the tumor tissue and explain some barriers and limitations that exist in the use of HDLs as an ideal delivery vehicle.

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Intracellular Drug Delivery by Genetically Engineered High-Density Lipoprotein Nanoparticles

Abstract: The genetic fusion of apoA-I with biologically active peptides potentially enables a simple assembly of biocompatible and versatile drug carriers.

Cited by 45 publications

References 33 publications

Fatty acids as therapeutic auxiliaries for oral and parenteral formulations

Fatty acids as therapeutic auxiliaries for oral and parenteral formulations

Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles

The role of high‐density lipoproteins in antitumor drug delivery

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