Strategies for improving the intratumoral distribution of liposomal drugs in cancer therapy

Abstract

Introduction A major limitation of current liposomal cancer therapies is the inability of liposome therapeutics to penetrate throughout the entire tumor mass. This inhomogeneous distribution of liposome therapeutics within the tumor has been linked to treatment failure and drug resistance. Both liposome particle transport properties and tumor microenvironment characteristics contribute to this challenge in cancer therapy. This limitation is relevant to both intravenously and intratumorally administered liposome therapeutics. Areas covered Strategies to improve the intratumoral distribution of liposome therapeutics are described. Combination therapies of intravenous liposome therapeutics with pharmacologic agents modulating abnormal tumor vasculature, interstitial fluid pressure, extracellular matrix components, and tumor associated macrophages are discussed. Combination therapies using external stimuli (hyperthermia, radiofrequency ablation, magnetic field, radiation, and ultrasound) with intravenous liposome therapeutics are discussed. Intratumoral convection-enhanced delivery (CED) of liposomal therapeutics is reviewed. Expert opinion Optimization of the combination therapies and drug delivery protocols are necessary. Further research should be conducted in appropriate cancer types with consideration of physiochemical features of liposomes and their timing sequence. More investigation of the role of tumor associated macrophages in intratumoral distribution is warranted. Intratumoral infusion of liposomes using CED is a promising approach to improve their distribution within the tumor mass.

Size and lipid modification determine liposomal Indocyanine green performance for tumor imaging in a model of rectal cancer

“…It is attributed to the location of the abnormal, leaky vessels in the tumor periphery and to the increased intratumoral, interstitial pressure which limits passive liposomal diffusion 23 . However, while the peripheral distribution of liposomes may impair their therapeutic efficacy as drug carriers 24 , it does not impair tumor imaging, in which tumor extent and border delineation are required. Theoretically, decreasing liposome size below 60 nm could improve its intra-tumoral diffusion and possibly enhance intratumoral distribution.…”

Highly Selective Photodynamic Therapy with a Short Drug-Light Interval Using a Cytotoxic Photosensitizer Porphyrus Envelope for Drug-Resistant Prostate Cancer Cells

“…Furthermore, tumor-specific PS delivery is known to be a promising strategy to further improve the accumulation efficacy and retention of the PS which is directly administrated into tumor tissue [34] [35]. Therefore, the possibility of intratumoral administration of PE in vivo trials probably provides higher selectivity in PDT with a short drug-light interval than in vitro experiments, as reported in this study.…”

Tumor Drug Penetration Measurements Could Be the Neglected Piece of the Personalized Cancer Treatment Puzzle

“…We will mostly discuss implications for large molecules, although many of these concepts hold for, and can be extended to, small molecules as well. Techniques for drug characteristics to improve drug penetration at each level (e.g., association to albumin to prolong systemic half‐life, convection‐enhanced delivery to improve tumor tissue penetration or changing affinity to the target to enhance target engagement) are beyond the scope of this article …”