Abstract
Emergence of various nanoscale drug carrier platforms as Drug Delivery Systems (DDS) has revolutionized the field of medicine.Nonetheless, theside-effects due to non-specific distribution of anticancer therapeutics in normal, healthy tissues remain to be a prime pitfall in curing cancers. Therefore, to achieve a better therapeutic efficacy, the use of a target-specific delivery, combined with a stimuli-responsive nanocarrier system, particularly pH-sensitive nanosystems offer an attractive strategy. Targeted drug delivery through pH-sensitive nanosystems offer the potential to enhance the therapeutic index of anticancer agents, either by increasing the drug concentration in tumor cells and/or by decreasing the exposure in normal host tissues. Therefore, nanoscale-based drug delivery through pH-sensitive nanosystems seem to be a boon for treating gynaecological cancers (as well as other cancers) without side-effects or with least harm to normal healthy tissues.
Highlights
A hope of successful treatment of cancers without side effects has challenged oncologists and onco-scientists since decades
In recent years, nanosized carriers have gained attention as unique drug delivery agents due to following qualities: (i) they have abilities to incorporate payloads with different solubilities [1], (ii) they improve the in vivo pharmacokinetics (PK) of drugs [2], (iii) they enhance bioavailabilities [3], and (iv) they modify the carriers with targeting ligands on their surface for tumor tissue or cell-specific delivery to minimize side-effects on healthy cells/ tissues [4]
NPs core coated with SiO2 with an imidazole group modified PEG-polypeptide, polyacrylic acid (PAA) and folic acid coating of the iron oxide NP core, methoxy polyethylene glycol-block-polymethacrylic acid-block-polyglycerol monomethacrylate (MPEG-b-PMAA-b-PGMA) attached by a PGMA block to a Fe3O4 core, PEG-modified polyamidoamine (PAMAM) dendrimer shell with Fe3O4 core and mesoporous silica coated on Fe3O4, mostly coated with an anticancer drug and used for controlled release of cytostatic drugs into the tumor site by means of pH change [100]
Summary
A hope of successful treatment of cancers without side effects has challenged oncologists and onco-scientists since decades. When exposed to weakly acidic tumor microenvironment, drug carrying pH-responsive nanoplatforms can generate physicochemical changes in their structure and surface characteristics, causing drug release or contrast enhancement at a particular pathological site [11, 12] This ease of controlled drug delivery at the desired site, has incepted the preliminary idea of developing pH-sensitive drug delivery nanosystems. In an attempt to develop targeted drug delivery systems with cancerous cell-specificity and controlled release function inside cancer cells, Miyazaki and colleagues have designed hyaluronic acid (HA)-based pH-sensitive polymers as multifunctional polymers. These polymers exhibited pH-sensitivity and targeting properties to cells expressing CD44 (a cancer cell surface marker). Further research studies on the therapeutic and clinical aspects of pH-sensitive liposomes are needed to enable their commercial utility in gynecological cancer treatment
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