Abstract
The increased research activity aiming at improved delivery of pharmaceutical molecules indicates the expansion of the field. An efficient therapeutic delivery approach is based on the optimal choice of drug-carrying vehicle, successful targeting, and payload release enabling the site-specific accumulation of the therapeutic molecules. However, designing the formulation endowed with the targeting properties in vitro does not guarantee its selective delivery in vivo. The various biological barriers that the carrier encounters upon intravascular administration should be adequately addressed in its overall design to reduce the off-target effects and unwanted toxicity in vivo and thereby enhance the therapeutic efficacy of the payload. Here, we discuss the main parameters of remote-controlled drug delivery systems: (i) key principles of the carrier selection; (ii) the most significant physiological barriers and limitations associated with the drug delivery; (iii) major concepts for its targeting and cargo release stimulation by external stimuli in vivo. The clinical translation for drug delivery systems is also described along with the main challenges, key parameters, and examples of successfully translated drug delivery platforms. The essential steps on the way from drug delivery system design to clinical trials are summarized, arranged, and discussed.
Highlights
The core study of new types of drug carriers on living systems remains challenging and requires the involvement and collaboration of diverse high-performing research teams, which are made up of specialists with a wide range of expertise: from natural scientists developing the product to managers introducing it to the market
In experiments in vivo on the breast cancer 4T1 bearing BALB/c mice, it was shown that this drug delivery systems (DDS) provides an enchased penetration ability into solid tumor tissue when intravenous injection is attended with AFM exposure of the tumor site, and the most therapeutic effect was reached in a combination of chemotherapy and magnetic hyperthermia treatment
The violent collapse of cavitation bubbles produces shock waves and fluid microjets [127,128] (Figure 6a). These cavitation-induced phenomena may result in a significant mechanical impact on drug delivery systems, which induces the release of the loaded drug, on the one hand, and improves, for instance, the tumor-site drug penetration, on the other hand, [129]
Summary
The core study of new types of drug carriers on living systems remains challenging and requires the involvement and collaboration of diverse high-performing research teams, which are made up of specialists with a wide range of expertise: from natural scientists developing the product to managers introducing it to the market. Carriers with the loaded drug showed significantly higher tumor suppression than free drugs due to the enhanced permeability and retention effect and the pH responsiveness of NPs. Three days after administration and a significant protein knockdown in both siRNA-RVG-9R-treated and siRNA-RVG exosome-treated mice was observed, resulting from a significant decrease in BACE1. For example, magnetic carriers loaded with an anticancer drug provide both drug targeting to tumor and hyperthermia functions [72]
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