Abstract
Ideally, antineoplastic treatment aims to selectively eradicate cancer cells without causing systemic toxicity. A great number of antineoplastic agents (AAs) are available nowadays, with well-defined therapeutic protocols. The poor bioavailability, non-selective action, high systemic toxicity, and lack of effectiveness of most AAs have stimulated the search for novel chemotherapy protocols, including technological approaches that provide drug delivery systems (DDS) for gold standard medicines. Nanostructured lipid carriers (NLC) are DDS that contain a core of solid and lipid liquids stabilised by surfactants. NLC have high upload capacity for lipophilic drugs, such as the majority of AAs. These nanoparticles can be prepared with a diversity of biocompatible (synthetic or natural) lipid blends, administered by different routes and functionalised for targeting purposes. This review focused on the research carried out from 2000 to now, regarding NLC formulations for AAs (antimetabolites, antimitotics, alkylating agents, and antibiotics) encapsulation, with special emphasis on studies carried out in vivo. NLC systems for codelivery of AAs were also considered, as well as those for non-classical drugs and therapies (natural products and photosensitisers). NLC have emerged as powerful DDS to improve the bioavailability, targeting and efficacy of antineoplastics, while decreasing their toxic effect in the treatment of different types of cancer.
Highlights
Gidwani et al [17] developed a MCT-Nanostructured lipid carriers (NLC) formulation optimised by design of experiments (DoE) with 93% EE that was stable for 180 days and tested it in vitro and in vivo
Confirming the lower systemic toxicity, animals that received the NLC formulations did not show changes in body weight, food intake, and inactive moving behaviour, which was opposite to naïve animals or those treated with free ETP
A prodrug (FU-stearic acid conjugate) was synthesised and after it was mixed with CIS and incorporated into the NLC functionalised with hyaluronic acid (HA) (HA-CIS/FU-NLC) as a strategy for selectively targeting gastric cancer cells
Summary
Cancer is the widespread name for a large group of diseases characterised by the uncontrolled proliferation of abnormal cells and further spread to organs or tissues [1]. Chemotherapy is claimed to have started in 1900, when the German chemist Paul Ehrlich tested several compounds for treating cancer in animals [2] It was in just 1942 that the first chemical for inducing tumour regression (nitrogen mustard, used systemically) was tested for the first time in humans [3]. There is a discussion in the literature regarding the criteria for AAs grouping, their indication for each kind of cancer is well established Despite their well-established uses, AAs are mostly highly toxic agents. Nanostructured lipid carriers (NLC) evolved from SLN but have a mixture of solid and liquid lipids Such lipid blends a1r.e3.rMeseptorincssiRbelegafrodrinthgeAsrttriuclcetsuwraitlhsAtanbtiilniteyopolafsNticLsCL,oaavdoedidininNgLliCpid crystallisation without etetrtpbyhaxxhelptepcaeigieoetgpifslndortFliieh(enreincanrmaisognstcttetrsgrt,deri(hotp–peiouenfsttuoephuetb2rrhlnen0mmsolecd0lasa,ei0e“denpsdramaessn.cngnsutaataaodltipnrnanhvtaotude)eecl.popiditppaptFhyhtdrilieodtagyroirssuucs2eft,il0rgilceaNcee2osns[v0,1cL2d.ah1iCaAnnI]eflnt.cmoridieLspesvhiicocqeeflonefavruwonaltiiSnhptddcsLoehye[lssNtn1eaihetp2artr.ea,iArut1dSschc3Aei,statne]vuNsat)rco,-rliejLislesdunuotdCtsei-thtcNpiinohesaleLincaonplfrCivfedeipode,watiifhnwdsbeegcypeecaedenuoorcanrabrnroruinelnsceitgoclrdhcaaassoseufs”ttotmriscesoluituorifipencnlbdterstihiduidlsateiir/ehnteisyldsne,ie,qetttaajhohsuuPsrciecsiusswrdhteibmipffvelMwiyitleeapiliilrojentoadiadhndgsr,l its drug interactions and in vivo actions [10,12]
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