AuNP-Liposome Nanocomposites: Rationale of Preparation: History
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Sourour Idoudi
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Roua Ismail
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Ousama Rachid
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Abdelbary Elhissi
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Alaaldin M Alkilany

AuNP are poor drug delivery candidates based on the lack of a reservoir or a matrix to load therapeutics. In fact, loading of therapeutics are limited to the surface of the AuNP, and thus the loading capacity is intrinsically less than other nanocarriers (lipidic or polymeric) on weight per weight bases. However, AuNP have excellent optical and thermal properties and has been proven as an excellent light absorber in the UV-vis region of the spectrum with excellent photothermal conversion efficiency to generate local heat that can be employed to fight nearby cancer cells or to induce drug delivery from the hosting matrix.

  • gold
  • nanoparticles
  • plasmonic
  • liposomes
  • lipid

1. Liposome Nanoparticles: The Host

In the recent years, liposomes have gained attention from researchers for their potential and diverse applications. In the 1940s, J.Y. Johnson has discovered the first artificially manufactured phospholipid vesicles (i.e., liposomes) for use as model in the pharmaceutical industry [1][2][3]. In the upcoming years, similar methods for creating liposomes were proposed by different researchers [4][5]. Liposomes are among the first nanocarrier systems to receive FDA-approvals (since 1995 for Doxil®) and one of the most biocompatible, convenient and least expensive nanocarrier systems to prepare with true presence in market and clinic [5][6][7][8]. Many factors play a major role in the preparation procedure of liposomes, including lipid and drug concentrations, stirring rate during preparation, and the use of organic solvent/antisolvent [9]. These factors are important to control because they may influence size and number of bilayers (lamellarity) of liposome, which in turn have major effects on drug encapsulation inside the liposomal nanocarrier, release rates an overall pharmacokinetics [1].
Preparation techniques of liposomes are linked with several advantages including their suitability for encapsulating thermo-sensitive drugs, avoidance of using toxic organic solvents, ability to remove the solvent completely, and offering a procedure that is environment-friendly [1][9]. There is a growing need to develop new drug delivery nanocarriers including liposomes because drugs that are marketed in the current pharmaceutical dosage forms are not fully efficient in treating some diseases [10]. Moreover, liposomes have been widely applied throughout the years for delivering hydrophobic drugs with improved bioavailability and controlled release profiles [11]. For instance, docetaxel is known as a very powerful antineoplastic and antiangiogenic agent [12]; however, its clinical applications are limited because of its poor water-solubility and high toxicity [13]. This issue was addressed through loading docetaxel into liposomal nanocarriers, solubilizing the drug, and achieving a controlled drug release formulation [14]. Doxil®, Myocet®, and Ambisome® are examples of liposomal-based therapies, in addition to many other products that are currently in use in the market [15][16][17][18][19]. Moreover, liposomes are widely applied for biomedical applications since they are biocompatible and biodegradable, have high tissue penetration, can serve as relatively safe drug nanocarriers, and can be manufactured and scaled up using established methods [1][10].
Biomedical applications of liposomes include breast cancer therapy [20], hepatocellular carcinoma [21], cancer Imaging [22], and Rheumatoid arthritis (RA) [23]. However, low solubility of drug-loaded liposomes can result in poor drug loading, high polydispersity of the nanoparticles, and unfeasibility for large-scale production; all these are among the drawbacks linked with the current preparation methods of liposomes [1][9][24]. In the recent years, liposomes gained an increased focus on developing liposome-based nanocomposite complexes that would reserve both exclusive properties of inorganic nanoparticles and the lipidic assembly compromising them [25]. In this regard, many studies tended to develop AuNP-liposome nanocomposites as an attempt to develop effective and potential nanocomposites for future biomedical applications.

2. AuNP-Liposome Nanocomposites: Rationale of Preparation

From material chemistry perspective, nanocomposites are hybrid material that are made of more than one types of materials to combine the advantages of composing components and/or to overcome the limitations/challenges associated with one or more of them [9][26][27]. It is worth to mention that the term “nanocomposite” implies that at least one component to be at the nanoscale. For example, carbon nanofiber and clay nanoplates are employed to reinforce various types of polymers and manipulate their mechanical properties while silver nanoparticles can be doped into textile matrix to provide them with antibacterial properties. Other systems imply the use of two or more materials at the nanoscale such as nano-in nano structures [28][29][30][31], where the discussed system (AuNP-liposome nanocomposites) fall into this category [32][33][34][35][36]. For example, AuNP are poor drug delivery candidates based on the lack of a reservoir or a matrix to load therapeutics. In fact, loading of therapeutics are limited to the surface of the AuNP, and thus the loading capacity is intrinsically less than other nanocarriers (lipidic or polymeric) on weight per weight bases [37]. However, AuNP have excellent optical and thermal properties and has been proven as an excellent light absorber in the UV-vis region of the spectrum with excellent photothermal conversion efficiency to generate local heat that can be employed to fight nearby cancer cells or to induce drug delivery from the hosting matrix. On the other end, liposome nanocarriers in general enjoy a complementing feature such as the ease of therapeutic loading to acceptable loading capacities and efficiencies. In fact, liposomes are one of the first nanoparticles to get FDA approvals (Doxil® in 1995) [18], and has been employed as a carrier for many therapeutics in the clinic [38][39]. Moreover, both hydrophilic and hydrophobic drugs can be loaded into the aqueous reservoir (Doxil®) or the bilayer membrane (Ambisome®) of the liposome, respectively [18][40]. Considering the features of both AuNP and liposome nanocarriers, it stimulates an interesting approach to prepare nanocomposite of both. One of the early works in this direction described the loading of electron-rich AuNP as a probe into liposomes to enable the visualization of the resulting AuNP-liposome nanocomposite under electron microscopy and thus understanding the liposome-cell interactions [41]. Moreover, encapsulation of AuNP as “nanoprobes” into liposome nanocarriers should help in quantifying the hosting lipid nanocarriers uptake into the cells using inductively coupled plasma mass spectrometry (ICP-MS) analysis. Other driving force is to load NIR-absorbing AuNP into liposomes to enable the fabrication of NIR-responsive lipid nanocarriers that can load therapeutics at acceptable loading capacity and release their payload on demand upon NIR laser irradiation [42][43][44][45]. In another direction, combining anticancer therapeutics and AuNP in the same liposome nanocarriers might enable synergistic anticancer activity via combing both chemo- and photo-thermal modalities [46]. Finally it is worth to mention that AuNP-liposome nanocomposite can be employed to improve the colloidal and physical stability of both the AuNP and liposomes [47][48][49]. For example, Runmei et al. have inhibited the aggregation of AuNP through preparing nanosized AuNP-liposome nanocomposite to increase steric hindrance [50]. AuNP modification by phospholipids has been stated to be capable of mitigating the acute cytotoxicity of metallic nanoparticles [51], and manipulating their endocytosis into cells [52]. Lee et al. reported the facile synthesis of AuNP with tunable optical properties inside the aqueous cavity of liposomes and confirmed the improved colloidal stability and cellular uptake of the AuNP-liposome nanocomposite compared to AuNP alone [52]. Collectively, AuNP-liposome nanocomposites would provide a new approach to combine both advantages from liposomes and AuNP, enabling their potential applications in various biomedical fields.

This entry is adapted from the peer-reviewed paper 10.3390/jnt4030010

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