Sustained Drug Release from Smart Nanoparticles in Cancer Therapy: A Comprehensive Review

Abstract

Although nanomedicine has been highly investigated for cancer treatment over the past decades, only a few nanomedicines are currently approved and in the market; making this field poorly represented in clinical applications. Key research gaps that require optimization to successfully translate the use of nanomedicines have been identified, but not addressed; among these, the lack of control of the release pattern of therapeutics is the most important. To solve these issues with currently used nanomedicines (e.g., burst release, systemic release), different strategies for the design and manufacturing of nanomedicines allowing for better control over the therapeutic release, are currently being investigated. The inclusion of stimuli-responsive properties and prolonged drug release have been identified as effective approaches to include in nanomedicine, and are discussed in this paper. Recently, smart sustained release nanoparticles have been successfully designed to safely and efficiently deliver therapeutics with different kinetic profiles, making them promising for many drug delivery applications and in specific for cancer treatment. In this review, the state-of-the-art of smart sustained release nanoparticles is discussed, focusing on the design strategies and performances of polymeric nanotechnologies. A complete list of nanomedicines currently tested in clinical trials and approved nanomedicines for cancer treatment is presented, critically discussing advantages and limitations with respect to the newly developed nanotechnologies and manufacturing methods. By the presented discussion and the highlight of nanomedicine design criteria and current limitations, this review paper could be of high interest to identify key features for the design of release-controlled nanomedicine for cancer treatment.

Hyaluronic Acid-Coated Chitosan Nanoparticles as an Active Targeted Carrier of Alpha Mangostin for Breast Cancer Cells

“…Due to the breakdown in the electrostatic balance between CS and TPP in AM-CS or between CS, TPP, and HA in -CS/HA in an acidic environment, AM release was larger at pH 5.5 than at pH 7.4. This pH-dependent release mechanism reduces the drug’s systemic toxicity due to decreased bioavailability in healthy organs at physiological pH, which could reduce drug side effects for patients [ 82 , 83 ]. Subsequently, pH-sensitive drug delivery systems result in higher bioavailability for drugs at tumor sites at acidic pH and increase their efficiency in malignant tissues [ 54 , 76 , 84 , 85 ].…”

Phytochemical-Based Nanomedicine for Targeting Tumor Microenvironment and Inhibiting Cancer Chemoresistance: Recent Advances and Pharmacological Insights

“…189−191 Therefore, most pharmaceutical researchers and industries adopted the nanotechnology-based drug delivery strategy for translational success and considered it an emerging technology to utilize more bioactive phytochemicals in mainstream medicine. 187,30,192 In the recent past, nanotechnology has offered novel approaches to cancer therapy, and several revolutionized nanodrugs available in the pharmaceutical market such as doxil, abraxane, mycocet, etc., prove to be showing better anticancer property than their native counterpart. Abraxane entered the market in 2005, due to its high efficacy and safety profile, and is used as first-line therapy for advanced breast cancer.…”

“…Despite the availability of several treatment options for cancer, chemotherapy is the first line treatment; however, due to cancer recurrence, drug resistance, and metastasis, chemotherapeutics are administered at higher doses to eliminate cancer, resulting in toxic effects on normal cells. , In this regard, several potential phytochemicals with multimodal anticancer properties are gaining much interest for use in anticancer therapy, either individually or in combination with chemotherapeutics. ,, However, translational success of phytochemicals remains low, and a number of phytochemicals have been withdrawn in different phases of clinical trials due to their inadequate drug profiles. , For example, when native curcumin was administered at a dose higher than 12 g in healthy volunteers, very low levels of curcumin were detected in the serum, resulting in poor bioavailability and thereby limiting its systemic cancer preventive activity . Recently, nanotechnology has gained much attention for improving the intrinsic profiles of these potential phytochemicals to be used as anticancer agents. − Therefore, most pharmaceutical researchers and industries adopted the nanotechnology-based drug delivery strategy for translational success and considered it an emerging technology to utilize more bioactive phytochemicals in mainstream medicine. ,, In the recent past, nanotechnology has offered novel approaches to cancer therapy, and several revolutionized nanodrugs available in the pharmaceutical market such as doxil, abraxane, mycocet, etc., prove to be showing better anticancer property than their native counterpart. Abraxane entered the market in 2005, due to its high efficacy and safety profile, and is used as first-line therapy for advanced breast cancer.…”

Controlled and Targeted Drug Delivery Using Smart Nanovectors

“…The list of efforts to develop a selective anticancer drug delivery is growing daily, with many of the above mentioned technologies being applied [50]. Two independent investigators developed a pH-responsive nanovector for doxorubicin (DOX) delivery to tumor tissues.…”