Therapeutic opportunities for targeted liposomal drug delivery

Allen, Theresa M.; Moase, Elaine H.

doi:10.1016/s0169-409x(96)00402-4

Cited by 113 publications

(62 citation statements)

References 65 publications

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“…Thus, associating a drug with liposomes markedly changes its pharmacokinetic and pharmacodynamic properties and lowers systemic toxicity; furthermore, the drug is prevented from early degradation and/or inactivation following introduction to the target organism. [6][7][8][9] In systemic administration, micelles or liposomes should satisfy several base requirements: high drug loading, biodegradability, long blood circulation times, slow plasma clearance, and controllable drug release profiles.…”

Section: Introductionmentioning

confidence: 99%

Target‐Selective Drug Delivery through Liposomes Labeled with Oligobranched Neurotensin Peptides

et al. 2011

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The structure and the in vitro behavior of liposomes filled with the cytotoxic drug doxorubicin (Doxo) and functionalized on the external surface with a branched moiety containing four copies of the 8-13 neurotensin (NT) peptide is reported. The new functionalized liposomes, DOPC-NT₄Lys(C₁₈)₂, are obtained by co-aggregation of the DOPC phospholipid with a new synthetic amphiphilic molecule, NT₄ Lys(C₁₈)₂, which contains a lysine scaffold derivatized with a lipophilic moiety and a tetrabranched hydrophilic peptide, NT8-13, a neurotensin peptide fragment well known for its ability to mimic the neurotensin peptide in receptor binding ability. Dynamic light scattering measurements indicate a value for the hydrodynamic radius (RH) of 88.3±4.4 nm. The selective internalization and cytotoxicity of DOPC-NT₄ Lys(C₁₈)₂ liposomes containing Doxo, as compared to pure DOPC liposomes, were tested in HT29 human colon adenocarcinoma and TE671 human rhabdomyosarcoma cells, both of which express neurotensin receptors. Peptide-functionalized liposomes show a clear advantage in comparison to pure DOPC liposomes with regard to drug internalization in both HT29 and TE671 tumor cells: FACS analysis indicates an increase in fluorescence signal of the NT₄-liposomes, compared to the DOPC pure analogues, in both cell lines; cytotoxicity of DOPC-NT₄ Lys(C₁₈)₂-Doxo liposomes is increased four-fold with respect to DOPC-Doxo liposomes in both HT29 and TE671 cell lines. These effects could to be ascribed to the higher rate of internalization for DOPC-NT₄ Lys(C₁₈)₂-Doxo liposomes, due to stronger binding driven by a lower dissociation constant of the NT₄-liposomes that bind the membrane onto a specific protein, in contrast to DOPC liposomes, which approach the plasma membrane unselectively.

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Section: Introductionmentioning

confidence: 99%

Target‐Selective Drug Delivery through Liposomes Labeled with Oligobranched Neurotensin Peptides

et al. 2011

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“…Liposomes are excellent carrier systems for a variety of applications and are particularly ideal for drug delivery to the body due to the similarity to natural cells. The therapeutic index of drugs can be increased through incorporation into liposomes, which can act as a non-toxic, biodegradable system for solubilising drugs which have low aqueous solubility; protect rapidly degrading drugs from breakdown and consequently increase the drug residence time in the body; and also decrease drug toxicity (1). Delivery of drugs using liposomes also reduces the accumulation of drugs in sensitive tissues; alters the biodistribution and controls the release of an incorporated drug, therefore improving bioavailability; as well as targets the drug to specific tissue (1).…”

Section: Introductionmentioning

confidence: 99%

Conventional and Dense Gas Techniques for the Production of Liposomes: A Review

2008

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Abstract. The aim of this review paper is to compare the potential of various techniques developed for production of homogenous, stable liposomes. Traditional techniques, such as Bangham, detergent depletion, ether/ethanol injection, reverse-phase evaporation and emulsion methods, were compared with the recent advanced techniques developed for liposome formation. The major hurdles for scaling up the traditional methods are the consumption of large quantities of volatile organic solvent, the stability and homogeneity of the liposomal product, as well as the lengthy multiple steps involved. The new methods have been designed to alleviate the current issues for liposome formulation. Dense gas liposome techniques are still in their infancy, however they have remarkable advantages in reducing the use of organic solvents, providing fast, single-stage production and producing stable, uniform liposomes. Techniques such as the membrane contactor and heating methods are also promising as they eliminate the use of organic solvent, however high temperature is still required for processing.

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“…To form targeted liposomes, monoclonal antibodies (mAbs), peptides, or growth factors that bind selectively to tumor-associated surface antigens or receptors are coupled to the liposome surface (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Antibodies or antibody fragments that are capable of inducing efficient receptor-mediated internalization of immunoliposomes can result in significant increases in the amount of drug delivered to the target cells and enhanced therapeutic outcomes relative to free drugs, noninternalizing antibodies, or nontargeted liposomes (13)(14)(15). In addition, many mAbs have unique signaling properties, such as inhibition of DNA repair (16), blockade of P-glycoprotein (17), or induction of apoptosis (18), that lead to anticancer effects that may synergize with the cytotoxic effects of liposomal anticancer drugs (19 -21).…”

Section: Introductionmentioning

confidence: 99%