The Utility of Lipids as Nanocarriers and Suitable Vehicle in Pharmaceutical Drug Delivery

Author(s): Salome A. Chime*, Paul A. Akpa, Anthony A. Attama

Journal Name: Current Nanomaterials

Volume 4 , Issue 3 , 2019

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Graphical Abstract:


Lipid based excipients have gained popularity recently in the formulation of drugs in order to improve their pharmacokinetic profiles. For drugs belonging to the Biopharmaceutics Classification System (BCS) class II and IV, lipid excipients play vital roles in improving their pharmacokinetics properties. Various nanocarriers viz: Solid lipid nanoparticles, nanostructured lipid carriers, selfnanoemulsifying drug delivery systems (SNEDDS), nanoliposomes and liquid crystal nanoparticles have been employed as delivery systems for such drugs with evident successes. Lipid-based nanotechnology have been used to control the release of drugs and have utility for drug targeting and hence, have been used for the delivery of various anticancer drugs and for colon targeting. Drugs encapsulated in lipids have enhanced stability due to the protection they enjoy in the lipid core of these nanoformulations. However, lipid excipients could be influenced by factors which could affect the physicochemical properties of lipid-based drug delivery systems (LBDDS). These factors include the liquid crystalline phase transition, lipid crystallization and polymorphism amongst others. However, some of the physicochemical properties of lipids made them useful as nanocarriers in the formulation of various nanoformulations. Lipids form vesicles of bilayer which have been used to deliver drugs and are often referred to as liposomes and nanoliposomes. This work aims at reviewing the different classes of lipid excipients used in formulating LBDDS and nanoformulations. Also, some factors that influence the properties of lipids, different polymorphic forms in lipid excipients that made them effective nanocarriers in nano-drug delivery would be discussed. Special considerations in selecting lipid excipients used in formulating various forms of nanoformulations would be discussed.

Keywords: Lipids, polymorphism, solid lipid nanoparticles, nanoliposomes, nanostructured lipid carriers, drug delivery.

Nanjwade BK, Patel DJ, Udhani RA, Manvi FV. Functions of lipids for enhancement of oral bioavailability of poorly water-soluble drugs. Sci Pharm 2011; 79(4): 705-27.
[] [PMID: 22145101]
Obitte NC, Chime SA, Magaret AA, et al. Some in vitro and pharmacodynamic evaluation of indomethacin solid lipid microparticles. Afr J Pharm Pharmacol 2012; 6(30): 2309-17.
Chime SA, Onyishi IV. Lipid-based drug delivery systems (LDDS): recent advances and applications of lipids in drug delivery. Afr J Pharm Pharmacol 2013; 7(48): 3034-59.
Chime SA, Attama AA, Builders PF, Onunkwo GC. Sustained-release diclofenac potassium-loaded solid lipid microparticle based on solidified reverse micellar solution: in vitro and in vivo evaluation. J Microencapsul 2013; 30(4): 335-45.
[] [PMID: 23057661]
Müller RH, Mäder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art. Eur J Pharm Biopharm 2000; 50(1): 161-77.
[] [PMID: 10840199]
Ragwa MF, Noha SE, Amal HE, et al. Lipid-based nanocarriers for ocular drug delivery. In: Andronescu E, Grumezescu AM, Eds. Nanostructures for Drug Delivery. Elsevier: The Netherlands 2017; pp. 495-522.
Kenechukwu FC, Attama AA, Emmanuel CI, et al. Novel intravaginal drug delivery system based on molecularly pegylated lipid matrices for improved antifungal activity of miconazole nitrate. BioMed Res Int 2018; 2018: 1-18.
[] [PMID: 29977910]
Khan A, Aqil M, Imam SS, et al. Temozolomide loaded nano lipid based chitosan hydrogel for nose to brain delivery: characterization, nasal absorption, histopathology and cell line study. Int J Biol Macromol 2018; 116: 1260-7.
[] [PMID: 29775717]
Moazeni M, Kelidari HR, Saeedi M, et al. Time to overcome fluconazole resistant Candida isolates: solid lipid nanoparticles as a novel antifungal drug delivery system. Colloids Surf B Biointerfaces 2016; 142: 400-7.
[] [PMID: 26974361]
Li W. Lipid formulation: successful stories and prospective future. Trends Bio Pharma Ind 2006; 3: 31-5.
Umeyor EC, Kenechukwu FC, Ogbonna JD, Chime SA, Attama A. Preparation of novel solid lipid microparticles loaded with gentamicin and its evaluation in vitro and in vivo. J Microencapsul 2012; 29(3): 296-307.
[] [PMID: 22283701]
Attama AA, Momoh MA, Builders PF. Lipid nanoparticulate drug delivery systems: a revolution in dosage form design and development, recent advances in novel drug carrier systems. InTech: United Kingdom 2012.
Attama AA, Okafor CE, Builders PF, Okorie O. Formulation and in vitro evaluation of a PEGylated microscopic lipospheres delivery system for ceftriaxone sodium. Drug Deliv 2009; 16(8): 448-57.
[] [PMID: 19839789]
Attama AA, Nkemnele MO. In vitro evaluation of drug release from self micro-emulsifying drug delivery systems using a biodegradable homolipid from Capra hircus. Int J Pharm 2005; 304(1-2): 4-10.
[] [PMID: 16198521]
Gelperina S, Kisich K, Iseman MD, Heifets L. The potential advantages of nanoparticle drug delivery systems in chemotherapy of tuberculosis. Am J Respir Crit Care Med 2005; 172(12): 1487-90.
[] [PMID: 16151040]
Chime SA, Onyishi VI. Solidified reverse micellar solutions (SRMS): a novel approach for controlling drug release from various lipids based drug delivery systems. Afr J Biotechnol 2013; 1(52): 7138-46.
Chen Y, Ma P, Gui S. Cubic and hexagonal liquid crystals as drug delivery systems. BioMed Res Int 2014; 2014: 1-12.
Alvarez AMR, Rodríguez MLG. Lipids in pharmaceutical and cosmetic preparations. Grasas Aceites 2000; 51(1-2): 74-96.
Small DM, Zoeller RA. Lipids: structure and biochemistry. Ed. In: Meyers RA, Encyclopedia of of molecular biology and biotechnology. Wiley VCH: New York 1995, 440-509.
Stuchlík M, Zák S. Lipid-based vehicle for oral drug delivery. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2001; 145(2): 17-26.
[] [PMID: 12426768]
Fahy E, Sud M, Cotter D, Subramaniam S. LIPID MAPS online tools for lipid research. Nucleic Acids Res 2007; 35(Suppl. 2).W606-12
[] [PMID: 17584797]
Kulkarni CV. Lipid crystallization: from self-assembly to hierarchical and biological ordering. Nanoscale 2012; 4(19): 5779-91.
[] [PMID: 22899223]
Ribeiro APB, Masuchi MH, Miyasaki EK, et al. Crystallization modifiers in lipid systems. J Food Sci Technol 2015; 52(7): 3925-46.
[] [PMID: 26139862]
Scrimgeour C. Chemistry of Fatty Acids: Bailey's Industrial Oil and Fat Products, 6th ed. Wiley: New York, 2005; Part 11-43.
O’Brien RD. Fats and oils-formulating and processing for applications. CRC Press: New York 2008; pp. 1-680.
Cullis PR, David BF, Michael JH. Physical properties and functional roles of lipids in membranes in biochemistry of lipids, lipoproteins and membranes. Elsevier: The Netherlands 1996; pp. 1-33.
Li J, Wang X, Zhang T, et al. A review on phospholipids and their main applications in drug delivery systems. Asian J Pharm Sci 2015; 10(2): 81-98.
Tanaka Y, Schroit AJ. Insertion of fluorescent phosphatidylserine into the plasma membrane of red blood cells: recognition by autologous macrophages. J Biol Chem 1983; 258(18): 11335-43.
Hope MJ, Nayar R, Mayer LD, et al. In: Gregoriadis G Ed. Reduction of liposome size and preparation of unilamellar vesicles by extrusion techniques -liposome technology, Vol. I: liposome preparation and related techniques. CRC Press: London, 1993: pp. 123- 139.
Israelachvili J. The science and applications of emulsions-an overview. Colloids Surf A Physicochem Eng Asp 1994; 91(3): 1-8.
Gonnade YR, Niranjane K, Arati A. Lipid: an emerging platform for lipid based drug delivery system World J Pharm Pharmaceut 3(4): 572-89.
Sagalowicz L, Leser ME, Watzke HJ, Michel M M. (2006a). Monoglyceride self-assembly structures as delivery vehicles. Trends Fd Sci Tech 2014; 17(5): 204-14.
Sagalowicz L, Mezzenga R, Leser ME. Investigating reversed liquid crystalline mesophases. Cur Opn Col Int Sci 2006; 11(4): 224-9.
Clogston J, Caffrey M. Controlling release from the lipidic cubic phase. Amino acids, peptides, proteins and nucleic acids. J Control Release 2005; 107(1): 97-111.
[] [PMID: 15990192]
Mezzenga R, Schurtenberger P, Burbidge A, Michel M. Understanding foods as soft materials. Nat Mater 2005; 4(10): 729-40.
[] [PMID: 16195765]
Mohammady SZ, Pouzot M, Mezzenga R. Oleoylethanolamide- based lyotropic liquid crystals as vehicles for delivery of amino acids in aqueous environment. Biophys J 2009; 96(4): 1537-46.
Lee DR, Park JS, Bae IH, Lee Y, Kim BM. Liquid crystal nanoparticle formulation as an oral drug delivery system for liver-specific distribution. Int J Nanomedicine 2016; 11: 853-71.
[PMID: 27042053]
Guo C, Wang J, Cao F, Lee RJ, Zhai G. Lyotropic liquid crystal systems in drug delivery. Drug Discov Today 2010; 15(23-24): 1032-40.
[] [PMID: 20934534]
Alving CR, Beck Z, Matyas GR, Rao M. Liposomal adjuvants for human vaccines. Exp Opin Dr Del 2016; 13(6): 807-16.
Anuhya B. Liposomes as potential carriers in drug delivery, gene delivery and preparation, formulation and evaluation of liposomes. J Pharm Res 2012; 5(2): 1210-6.
Avdeef A, Artursson P, Neuhoff S, Lazorova L, Gråsjö J, Tavelin S. Caco-2 permeability of weakly basic drugs predicted with the double-sink PAMPA pKa(flux) method. Eur J Pharm Sci 2005; 24(4): 333-49.
[] [PMID: 15734300]
Bermejo M, Avdeef A, Ruiz A, et al. PAMPA--a drug absorption in vitro model 7. Comparing rat in situ, Caco-2, and PAMPA permeability of fluoroquinolones. Eur J Pharm Sci 2004; 21(4): 429-41.
[] [PMID: 14998573]
Dagenais C, Avdeef A, Tsinman O, Dudley A, Beliveau R. P-glycoprotein deficient mouse in situ blood-brain barrier permeability and its prediction using an in combo PAMPA model. Eur J Pharm Sci 2009; 38(2): 121-37.
[] [PMID: 19591928]
Rangel-Yagui CO, Pessoa A Jr, Tavares LC. Micellar solubilization of drugs. J Pharm Pharm Sci 2005; 8(2): 147-65.
[PMID: 16124926]
Dutt GB. Rotational diffusion of hydrophobic probes in Brij-35 micelles: effect of temperature on micellar internal environment. J Phys Chem B 2003; 107: 10546-51.
Mall S, Buckton G, Rawlins DA. Dissolution behaviour of sulphonamides into sodium dodecyl sulfate micelles: a thermodynamic approach. J Pharm Sci 1996; 85(1): 75-8.
[] [PMID: 8926588]
Canto GS, Dalmora SL, Oliveira AG. Piroxicam encapsulated in liposomes: characterization and in vivo evaluation of topical anti-inflammatory effect. Drug Dev Ind Pharm 1999; 25(12): 1235-9.
[] [PMID: 10612018]
Torchilin VP. Structure and design of polymeric surfactant-based drug delivery systems. J Control Release 2001; 73(2-3): 137-72.
[] [PMID: 11516494]
Papaioannou AI, Papiris S, Papadaki G, et al. Surfactant proteins in smoking-related lung disease. Curr Top Med Chem 2016; 16(14): 1574-81.
[] [PMID: 26420367]
Kabanov AV, Nazarova IR, Astafieva IV, et al. Micelle formation and solubilization of fluorescent probes in poly(oxyethylene-b-oxypropylene-b-oxyethylene) solutions. Macromol 1995; 28: 2303-14.
Aoun B, Sharma VK, Pellegrini E, Mitra S, Johnson M, Mukhopadhyay R. Structure and dynamics of ionic micelles: MD simulation and neutron scattering study. J Phys Chem B 2015; 119(15): 5079-86.
[] [PMID: 25803564]
Hanafy NAN, El-Kemary M, Leporatti S. Micelles structure development as a strategy to improve smart cancer therapy. Cancers (Basel) 2018; 10(7): 1-14.
[] [PMID: 30037052]
Gao P, Morozowich W. Development of supersaturatable self-emulsifying drug delivery system formulations for improving the oral absorption of poorly soluble drugs. Expert Opin Drug Deliv 2006; 3(1): 97-110.
[] [PMID: 16370943]
Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995; 12(3): 413-20.
[] [PMID: 7617530]
Yano K, Masaoka Y, Kataoka M, Sakuma S, Yamashita S. Mechanisms of membrane transport of poorly soluble drugs: role of micelles in oral absorption processes. J Pharm Sci 2010; 99(3): 1336-45.
[] [PMID: 19743502]
Das S, Chaudhury A. Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery. AAPS PharmSciTech 2011; 12(1): 62-76.
[] [PMID: 21174180]
Censi R, Di Martino P. Polymorph impact on the bioavailability and stability of poorly soluble drugs. Molecules 2015; 20(10): 18759-76.
[] [PMID: 26501244]
Boistelle R. Crystallization and polymorphism of fats and fatty acids. Marcel Dekker: New York 1988; pp. 189-226.
Foubert I. The lipid handbook. 3rd ed. CRC Press: Boca Raton 2007; pp. 415-69.
Lawler PJ, Dimick PS. Food lipids: chemistry, nutrition, and biotechnology. CRC Press: Boca Raton 2002; pp. 275-300.
Metin S, Hartel RW. Crystallization of Fats and Oils. Wiley Interscience: New York 2005; pp. 45-76.
Wright AJ, Narine SS, Marangoni AG. Comparison of experimental techniques used in lipid crystallization studies. J Am Oil Chem Soc 2000; 77: 1239-42.
Wright AJ, Marangoni AG. Effect of DAG on milk fat TAG crystallization. J Am Oil Chem Soc 2002; 79: 395-402.
Sato K. Crystallization behavior of fats and lipids: a review. Chem Eng Sci 2001; 56: 2255-65.
Sato K, Bayés-García L, Calvet T, et al. External factors affecting polymorphic crystallization of lipids. Eur J Lipid Sci Technol 2013; 115(11): 1224-38.
Attama AA, Schicke BC, Müller-Goymann CC. Further characterization of theobroma oil-beeswax admixtures as lipid matrices for improved drug delivery systems. Eur J Pharm Biopharm 2006; 64(3): 294-306.
[] [PMID: 16949805]
Aree T, Chaichit N, Engkakul C. Polymorphism in β-cyclodextrin-benzoic acid inclusion complex: a kinetically controlled crystal growth according to the Ostwald’s rule. Carbohydr Res 2008; 343(14): 2451-8.
[] [PMID: 18653173]
Llinàs A, Goodman JM. Polymorph control: past, present and future. Drug Discov Today 2008; 13(5-6): 198-210.
[] [PMID: 18342795]
Bunjes H, Koch MHJ. Saturated phospholipids promote crystallization but slow down polymorphic transitions in triglyceride nanoparticles. J Control Release 2005; 107(2): 229-43.
[] [PMID: 16023752]
Omar Z, Let CC, Seng CC, et al. Crystallisation and rheological properties of hydrogenated palm oil and palm oil blends in relation to crystal networking. Eur J Lipid Sci Technol 2005; 107(9): 634-40.
Padar S, Jeelani SAK, Windhab J. Crystallization kinetics of cocoa fat systems: experiments and modeling. J Am Oil Chem Soc 2008; 85: 1115-26.
Garti N. Physical properties of lipids. CRC Press: Boca Raton 2002; pp. 85-123.
Miskandar MS, Cheman AB, Abdulrahman R, et al. Effects of emulsifiers on crystallization properties of low-melting blends of palm oil and olein. J Food Lipids 2006; 13(1): 57-72.
Aronhime JS, Sarig S, Garti N. Mechanistic considerations of polymorphic transformations of tristearin in the presence of emulsifiers. J Am Oil Chem Soc 1987; 64: 529-33.
Lonchampt P, Hartel RW. Fat bloom in chocolate and compound coatings. Eur J Lipid Sci Technol 2004; 106: 241-74.
Sakamoto M, Ohba A, Kuriyama J, Maruo K, Ueno S, Sato K. Influences of fatty acid moiety and esterification of polyglycerol fatty acid esters on the crystallization of palm mid fraction in oil-in-water emulsion. Colloids Surf B Biointerfaces 2004; 37(1-2): 27-33.
[] [PMID: 15450305]
Garbolino C, Bartoccini M, Floeter E. The influence of emulsifiers on the crystallisation behaviour of a palm oilbased blend. Eur J Lipid Sci Technol 2005; 107: 616-26.
Wassell P, Okamura A, Young NWG, et al. Synchrotron radiation macrobeam and microbeam X-ray diffraction studies of interfacial crystallization of fats in water-in-oil emulsions. Langmuir 2012; 28(13): 5539-47.
[] [PMID: 22339396]
Maleky F, Campos R, Marangoni AG. Structural and mechanical properties of fats quantified by ultrasonics. J Am Oil Chem Soc 2007; 84: 331-8.
Santacatalina JV, Garcia-Perez JV, Corona E, et al. Ultrasonic monitoring of lard crystallization during storage. Food Res Int 2011; 44: 146-55.
Wagh A, Walsh MK, Martini S. Effect of lactose monolaurate and high intensity ultrasound on crystallization behavior of anhydrous milk fat. J Am Oil Chem Soc 2013; 90: 977-87.
Loisel C, Lecq G, Bourgaux C, et al. Phase transitions and polymorphism of cocoa butter. J Am Oil Chem Soc 1998; 75: 425-39.
Pouton CW. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci 2006; 29(3-4): 278-87.
[] [PMID: 16815001]
Pouton CW, Porter CJ. Formulation of lipid-based delivery systems for oral administration: materials, methods and strategies. Adv Drug Deliv Rev 2008; 60(6): 625-37.
[] [PMID: 18068260]
Cerpnjak K, Zvonar A, Gašperlin M, Vrečer F. Lipid-based systems as a promising approach for enhancing the bioavailability of poorly water-soluble drugs. Acta Pharm 2013; 63(4): 427-45.
[] [PMID: 24451070]
Chime SA, Attama AA, Onunkwo GC. Sustained release indomethacin-loaded solid lipid microparticles, based on solidified reverse micellar solution (SRMS): in vitro and in vivo evaluation. J Drug Deliv Sci Technol 2012; 22(5): 485-92.
Chime SA, Onyishi IV, Eze IO. Application of molecularly structured ben oil in gentamicin entrapped lipospheres. J Pharm Sci Therap 2019; 5(1): 262-70.
Porter CJH, Pouton CW, Cuine JF, Charman WN. Enhancing intestinal drug solubilisation using lipid-based delivery systems. Adv Drug Deliv Rev 2008; 60(6): 673-91.
[] [PMID: 18155801]
Shrestha H, Bala R, Arora S. Lipid-based drug delivery systems. J Pharm (Cairo) 2014; 2014801820
[] [PMID: 26556202]
Garg BJ, Garg NK, Beg S, Singh B, Katare OP. Nanosized ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery against vitiligo: formulation optimization, in vitro evaluation and preclinical assessment. J Drug Target 2016; 24(3): 233-46.
[] [PMID: 26267289]
Nagaich U, Gulati N. Nanostructured lipid carriers (NLC) based controlled release topical gel of clobetasol propionate: design and in vivo characterization. Drug Deliv Transl Res 2016; 6(3): 289-98.
[] [PMID: 27072979]
Charman SA, Charman WN, Rogge MC, Wilson TD, Dutko FJ, Pouton CW. Self-emulsifying drug delivery systems: formulation and biopharmaceutic evaluation of an investigational lipophilic compound. Pharm Res 1992; 9(1): 87-93.
[] [PMID: 1589415]
Shah NH, Carvajal MT, Patel CI. Self-emulsifying drug delivery systems (SEDDS) with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs. Int J Pharm 1994; 106: 15-23.
Kovarik JM, Mueller EA, van Bree JB, Tetzloff W, Kutz K. Reduced inter- and intraindividual variability in cyclosporine pharmacokinetics from a microemulsion formulation. J Pharm Sci 1994; 83(3): 444-6.
[] [PMID: 8207699]
Khopade AJ, Jain NK. Long-circulating lipospheres targeted to the inflammed tissue. Pharmazie 1997; 52(2): 165-6.
[PMID: 9122278]
Hauss DJ. Lipid-based systems for oral drug delivery: Enhancing the bioavailability of poorly water-soluble drugs. Am Pharm Rev 2002; 5: 22-8.
Porter CJH, Charman WN. Uptake of drugs into intestinal lymphatics after oral administration. Adv Drug Deliv Rev 1997; 25: 71-90.
Porter CJ, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discov 2007; 6(3): 231-48.
[] [PMID: 17330072]
Shackleford DM, Porter CJH, Charman WN. Problems addressable by prodrugsProdrugs: Challenges and Rewards. Springer: AAPS Press 2006; p. 657.
Dahan A, Hoffman A. Rationalizing the selection of oral lipid based drug delivery systems by an in vitro dynamic lipolysis model for improved oral bioavailability of poorly water soluble drugs. J Control Release 2008; 129(1): 1-10.
[] [PMID: 18499294]
Humberstone AJ, Charman WN. Lipid-based vehicles for the oral delivery of poorly water-soluble drugs. Adv Drug Deliv Rev 1997; 25: 103-28.
Friedrich I, Müller-Goymann CC. Characterization of solidified reverse micellar solutions (SRMS) and production development of SRMS-based nanosuspensions. Eur J Pharm Biopharm 2003; 56(1): 111-9.
[] [PMID: 12837489]
Friedrich I, Papantoniou I, Müller-Goymann CC. Physicochemical characterization of a reverse micellar solution after loading with different drugs. Pharmazie 2000; 55(10): 755-8.
[PMID: 11082837]

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Article Details

Year: 2019
Published on: 11 November, 2019
Page: [160 - 175]
Pages: 16
DOI: 10.2174/2405461504666191016091827

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