Abstract
Drug delivery to malignant tumors is limited by several factors, including off-target toxicities and suboptimal benefits to cancer patient. Major research efforts have been directed toward developing novel technologies involving nanoparticles (NPs) to overcome these challenges. Major obstacles, however, including, opsonization, transport across cancer cell membranes, multidrug-resistant proteins, and endosomal sequestration of the therapeutic agent continue to limit the efficiency of cancer chemotherapy. Lipoprotein-based drug delivery technology, “nature’s drug delivery system,” while exhibits highly desirable characteristics, it still needs substantial investment from private/government stakeholders to promote its eventual advance to the bedside. Consequently, this review focuses specifically on the synthetic (reconstituted) high-density lipoprotein rHDL NPs, evaluating their potential to overcome specific biological barriers and the challenges of translation toward clinical utilization and commercialization. This highly robust drug transport system provides site-specific, tumor-selective delivery of anti-cancer agents while reducing harmful off-target effects. Utilizing rHDL NPs for anti-cancer therapeutics and tumor imaging revolutionizes the future strategy for the management of a broad range of cancers and other diseases.
Highlights
Our laboratory has been engaged in reconstituted high-density lipoproteins drug delivery research for more than a decade, focusing on formulating and evaluating rHDL drug delivery vehicles for a multitude of anti-cancer agents
There are several classes of lipoproteins (VLDL, IDL, LDL, and HDL) in the blood of mammals, the present paper focuses only on high-density lipoproteins because of their preferred use in drug delivery research (Ng et al, 2011; Kuai et al, 2016)
RHDL NPs are inherently capable of overcoming several biological barriers to cancer therapy
Summary
Our laboratory has been engaged in reconstituted high-density lipoproteins (rHDL) drug delivery research for more than a decade, focusing on formulating and evaluating rHDL drug delivery vehicles for a multitude of anti-cancer agents. RHDL Delivery: Overcoming Biological Barriers their efforts toward developing rHDL-based formulations to deliver anti-cancer agents to malignant tumors, facilitated by the SR-B1 receptor. While developing/designing a nanoparticulate system for cancer therapy, several biological barriers remain as recently discussed by Blanco et al (2015) This communication deals with specific biological/physiological challenges based on the innate ability of the rHDL drug delivery platform to overcome them and considering optimization strategies to improve the drug delivery performance of rHDL. The rHDL NPs, Apo A-1 protein, and its mimetic peptides are known to have anti-inflammatory and anti-apoptotic properties This feature of potential HDL therapeutics has been reviewed by Barter et al (2004) and Navab et al (2007). We are focusing on the challenges (immune system, hemodynamics, cell membrane transport, and drug resistance) faced by drug delivery systems and how these barriers may be effectively overcome by the rHDL platform for cancer therapy
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