Drug delivery vehicles on a nano-engineering perspective

Felice, Betiana; Prabhakaran, Molamma P.; Rodrı́guez, Augusto; Ramakrishna, Seeram

doi:10.1016/j.msec.2014.04.049

Cited by 205 publications

(115 citation statements)

References 219 publications

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“…They are valued for their biological and technological advantages as optimal delivery systems for biologically active substances, both in vitro and in vivo, and are considered to be the most successful drug-carrier system known to date. 4 During the two last decades, notable progress has been made, and several biomedical applications of liposomes are either in clinical trials or are about to be put on the market, while others have already been approved for public use. 5 Therefore, the goal of this review is not to undertake an exhaustive report on the plethora of data published on liposomes since their first synthesis in the 1960s, but to focus on some points that play a key role in the development of liposomal formulation for therapy.…”

Section: Introductionmentioning

confidence: 99%

Liposomes as nanomedical devices

Bozzuto¹,

Molinari²

2015

IJN

1,651

1,043

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Since their discovery in the 1960s, liposomes have been studied in depth, and they continue to constitute a field of intense research. Liposomes are valued for their biological and technological advantages, and are considered to be the most successful drug-carrier system known to date. Notable progress has been made, and several biomedical applications of liposomes are either in clinical trials, are about to be put on the market, or have already been approved for public use. In this review, we briefly analyze how the efficacy of liposomes depends on the nature of their components and their size, surface charge, and lipidic organization. Moreover, we discuss the influence of the physicochemical properties of liposomes on their interaction with cells, half-life, ability to enter tissues, and final fate in vivo. Finally, we describe some strategies developed to overcome limitations of the “first-generation” liposomes, and liposome-based drugs on the market and in clinical trials.

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Section: Introductionmentioning

confidence: 99%

Liposomes as nanomedical devices

Bozzuto¹,

Molinari²

2015

IJN

1,651

1,043

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“…32,33 Actively targeting nanoparticles to tumors with antibodies, as demonstrated in this study, can have significant advantages and improve efficacy compared to passive targeting alone. Designing new BsAbs that are able to efficiently target nanoparticles opens a new dimension in active nanoparticle targeting.…”

Section: Wwwtandfonlinecom 59 Mabsmentioning

confidence: 87%

“…There are a number of nanomedicines presently in clinical trials, with several of these targeted by antibodies. 32,33 NPs can carry drug payloads that include small molecule drugs, DNA or RNA. 2,30,34 Accumulation of the NPs at the tumor site by passive targeting decreases biodistribution, ideally localizing the therapeutic effects of the drug payload at the tumor site(s).…”

Section: Introductionmentioning

confidence: 99%

“…21 Although functional BsAbs capable of delivering the EDV TM nanocell were prepared, it was noted that multimer formation and the inability to control the ratio of mAbs bound to the protein A/G, which has 6 potential Fc-binding sites, rendered the targeting entity unsuitable for commercial manufacture and downstream clinical trials. 21,32 Recombinant BsAbs offer an advantage of producing one antibody with dual target binding capability.…”

Section: Introductionmentioning

confidence: 99%

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Nanocell targeting using engineered bispecific antibodies

Taylor

Howard

Jones

et al. 2015

mAbs

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There are many design formats for bispecific antibodies (BsAbs), and the best design choice is highly dependent on the final application. Our aim was to engineer BsAbs to target a novel nanocell (EnGeneIC Delivery Vehicle or EDV TM nanocell) to the epidermal growth factor receptor (EGFR). EDV TM nanocells are coated with lipopolysaccharide (LPS), and BsAb designs incorporated single chain Fv (scFv) fragments derived from an anti-LPS antibody (1H10) and an anti-EGFR antibody, ABX-EGF. We engineered various BsAb formats with monovalent or bivalent binding arms and linked scFv fragments via either glycine-serine (G4S) or Fc-linkers. Binding analyses utilizing ELISA, surface plasmon resonance, bio-layer interferometry, flow cytometry and fluorescence microscopy showed that binding to LPS and to either soluble recombinant EGFR or MDA-MB-468 cells expressing EGFR, was conserved for all construct designs. However, the Fc-linked BsAbs led to nanocell clumping upon binding to EDV TM nanocells. Clumping was eliminated when additional disulfide bonds were incorporated into the scFv components of the BsAbs, but this resulted in lower BsAb expression. The G4S-linked tandem scFv BsAb format was the optimal design with respect to EDV binding and expression yield. Doxorubicin-loaded EDV TM nanocells actively targeted with tandem scFv BsAb in vivo to MDA-MB-468-derived tumors in mouse xenograft models enhanced tumor regression by 40% compared to passively targeted EDV TM nanocells. BsAbs therefore provide a functional means to deliver EDV TM nanocells to target cells.

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“…Various drug carrier systems such as liposomes, micelles, nanoparticles, and nanorods are used to perform the desired release of the drugs having weak solubility and therefore, low bioavailability in the body, and to minimize the interaction of the drugs with the healthy tissues (3). Regarding these systems, the main encountered drawbacks are instability within the body, interaction with the healthy tissues, allowing absorption in the kidneys due to nano sizes, and thus, expelling out the blood circulation (4,5).…”

Section: Introductionmentioning

confidence: 99%

New-generation Jeffamine® D230 core amine, TRIS and carboxylterminated PAMAM dendrimers: Synthesis, characterization and the solubility application for a model NSAID drug Ibuprofen

Ertürk¹,

Gürbüz²,

Tülü³

2017

Marmara Pharmaceutical Journal

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Many therapeutically active drugs are poor water soluble and, therefore, bioavailability of these molecules in the living cells is low and a major problem. In this study, new-generation Jeffamine ® D230 core, amine (NH 2 ), Tris(hydroxymethyl) aminomethane (TRIS), and carboxyl (COOH) terminated poly(amidoamine) PAMAM dendrimers (PAMAMs) were synthesized. Synthesized new-generation PAMAMs were characterized by 1 H NMR, 13 C NMR, ATR-FTIR, and investigated as solubility enhancer of a sample non-steroidal anti-inflammatory drug (NSAID) Ibuprofen (IBU). The effect of generation size (D2-D4), concentration (0-2.0 mM), and surface functional group (NH 2 , COOH, TRIS) of the synthesized new-generation PAMAMs on the aqueous solubility of IBU was also investigated. The observed solubility enhancement of IBU was in the order of D4.COOH (18.21 mg/mL)> D3.COOH (13.21 mg/mL)> D4.TRIS (10.30 mg/mL)> D2.COOH (8.55 mg/mL)> D3.TRIS (6.04 mg/mL)> D4.NH 2 (4.56 mg/mL)> D3.NH 2 (3.36 mg/mL)> D2.TRIS (2.42 mg/mL)> D2.NH 2 (1.86 mg/mL). Results showed that synthesized PAMAMs improved the solubility of IBU significantly (30 to 247-fold) with an increasing generation size, and concentration.

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Drug delivery vehicles on a nano-engineering perspective

Cited by 205 publications

References 219 publications

Liposomes as nanomedical devices

Liposomes as nanomedical devices

Nanocell targeting using engineered bispecific antibodies

New-generation Jeffamine® D230 core amine, TRIS and carboxylterminated PAMAM dendrimers: Synthesis, characterization and the solubility application for a model NSAID drug Ibuprofen

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