Abstract
This review explores the use of energy sources, including ultrasound, magnetic fields, and external beam radiation, to trigger the delivery of drugs from liposomes in a tumor in a spatially-specific manner. Each section explores the mechanism(s) of drug release that can be achieved using liposomes in conjunction with the external trigger. Subsequently, the treatment’s formulation factors are discussed, highlighting the parameters of both the therapy and the medical device. Additionally, the pre-clinical and clinical trials of each triggered release method are explored. Lastly, the advantages and disadvantages, as well as the feasibility and future outlook of each triggered release method, are discussed.
Highlights
Specific Liposomal Cancer Therapy Utilizing Medical Devices as Triggering MechanismThere are many factors that contribute to the successful treatment of cancer and maximize tumor control
A study by Evjen et al demonstrated a 30% increase in Dox release using DOPE liposomes compared to liposomes comprising DSPE, and a 9-fold improvement in release extent when compared to L-α-phosphatidylcholine (HSPC) pegylated liposome when irradiating with US for 6 min at 40 kHz [97]
The authors showed drug release from liposomes after treatment with short magnetic pulses that disrupted the lipid bilayer. They further concluded that drug release from mechanical disruption of the liposomes was less harmful to the drug payload as an increase in temperature could potentially damage the drug [148]
Summary
Radiation therapy is one of the most effective modes of cancer treatment given the recent advancements in defining the spatial precision and depth penetration of ionizing radiation. Using a delivery system where CPT is released locally at the irradiated site by X-rays would (1) minimize systemic chemotoxicity; (2) potentiate the efficacy of X-rays, and (3) potentially control the tumor with lower doses of radiation, chemotherapy, or both. The mechanism responsible for inducing the destabilization of the liposomal membrane is the radiosensitization effect [183,184], Figure 4 Radiosensitizers, such as gold nanoparticles, enhance the local radiation dose through the increased absorption of low and medium-energy X-rays and subsequent ejection of reactive secondary electrons [185]. There have been no direct studies examining the mechanisms of radiosensitization in conjunction with liposomes, in theory, the local production of hydroxyl radicals and secondary electrons mediated by embedded radiosensitizers should cause lipid peroxidation and liposomal bilayer destabilization when irradiated, thereby triggering drug release [183,184]. Tshhoewininitgiatlhuant dtreerasttmanednitnwgitohf gthoeldmneacnhoapnairstmiclebsehainnddXr-ardaiyocsaenussietitzuamtioornrwegarsesastitorinb,uotredinctorepasheydsiccealll fkaicllto[r1s8,9s]u. cThheasinthiteiahl iugnhdaetrosmtaincdniungmobferthaendmpechhoatoneislmectbriechcinrodssrasdeciotisoennsoiftigzaotlidon[19w0a].s MatotrnibteutCeadrltoo spihmyusliacatilofnasctworesr,esuucshedastothdeishciegrhnatthoemtyicpneuamndbenruamndbeprhooftoeleelcetcrtorincscermosisttseedctdioenpeonf dgionldg o[1n90v]a.rMiaobnletse sCuacrhloassimthuelasotiuorncse,wteyrpee,uasendd teonedrigscyeronf Xth-reatyysp, easanwdelnl uams tbheer soifzee,leccotnrocnens termatiiottne,dadnedpceonadtiinngg oonf gvoalrdianblaensospuacrhtiacsletsh.eGsoeunrecrea,ltlyy,piet, wanads efonuerngdy tohfaXt-srmayasl,lagsowldelnl aasntohpeasritzicel,ecsoantceanhtriagthiocno,nacnednctroaattiionng, wofhgeonldirrnaadnioapteadrtwiclieths. kGeeVneprhaolltyo,nitbweaams fso,ugnednethraattestmhealhl gigohldesnt aDnEoFpsa.rtHicolews eavtear,haigshthceonincevnivtroataionnd, iwnhveitnroirrraaddiioatseednswitiitzhatkieoVn epfhfeocttosnwbeeraemosf,tegnengerreaatteetrhtehahnigphreesdt iDctEeFds.DHEoFwveavlueer,sa, sitthhaesinnovwivobeacnodmien wvietlrlournaddeiorssteonosdititzhaattioconmefpfleecxtscwheemreicoaflteanndgrbeiaotleorgtihcaalninptreerdaiccttioednsD, sEuFchvaalsutehse, igt ehnaesrnatoiwonboefchomyderowxeylll ruanddicearslstoaosdmtheantticoonmedplaexbocvhee,maircealalasnodinbvioollovgeidcarlaidnitoesraecntsiiotnizsa, tsiounch, aansdthtehegreenfoerrea,tiroenquoifrehyfdurrothxeyrl irnavdeicstailgsaatisonm[e1n8t9i]o.ned above, are involved radiosensitization, and require further investigation [189]
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