Lipid Nanoparticles for Ocular Drug Delivery

Neslihan Üstündağ Okur, Evren Homan Gökçe

Neslihan Üstündağ Okur, Istanbul Medipol University, School of Pharmacy, Department of Pharmaceutical Technology, 34810 Beykoz, Istanbul, Turkey
Evren Homan Gökçe, Ege University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 35100 Bornova, Izmir, Turkey

Correspondence to: Evren Homan Gökçe, Ege University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 35100 Bornova, Izmir, Turkey.
Email: evrenhomangokce@gmail.com
Telephone: +90-232-3115132
Fax: +90-232-3885258
Received: September 15, 2015
Revised: October 9, 2015
Accepted: October 12, 2015
Published online: December 29, 2015


Despite numerous scientific efforts, efficient ocular drug delivery remains a challenge for pharmaceutical scientists. Delivery of ophthalmic drugs to the targeted ocular tissues is limited by many precorneal, dynamic and static ocular barriers. The anatomy, physiology and biochemistry of the eye render this organ exquisitely impervious to foreign substances. One of the promising strategies nowadays is the use of colloidal carrier systems characterized by a submicron-meter size. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) represent promising alternatives to conventional and very popular ocular carrier systems.

© 2015 ACT. All rights reserved.

Key words:Ocular drug delivery; Lipid nanoparticles; Solid lipid nanoparticles; Nanostructured lipid carriers; Eye

Okur NÜ, Gökçe EH. Lipid Nanoparticles for Ocular Drug Delivery. International Journal of Ophthalmic Research 2015; 1(3): 77-82 Available from: URL: http://www.ghrnet.org/index.php/ijor/article/view/1365


The ocular route is one of the most delicate routes of drug delivery due to the unique physicochemical conditions of the eye[1,2]. However, the eye poses unique challenges relative to drug delivery. A major problem in conventional ophthalmic drug delivery is low drug bioavailability due to ocular anatomical and physiological constraints, which include the poor permeability of cornea, nasolacrimal drainage effect, and short retention time in the precorneal area[3,4]. Excessive liquids, both normally produced and externally delivered, rapidly drain from the eye[5,6]. The approaches to overcome the barriers related to the ophthalmic drug delivery a major aim. During the last periods, numerous drug delivery systems, such as liposomes[7], nanoemulsions[8], microemulsions[4], nanoparticles[9] have emerged as novel strategies[10].

Nanoparticles - a sole subgroup of wide area of nanotechnology - are sized between 1 and 200 nanometers. Nanoparticles may or may not display size-related properties that vary significantly from particles or bulk materials and atomic or molecular structures[11]. Lipid nanoparticles, including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), are colloidal carriers with a lipid matrix. They are generally composed of lipids, surfactants and co-surfactants[12]. Lipid nanoparticles are alternative drug delivery systems to polymeric nanoparticles[13]. The lipid matrix is made from physiologically tolerated lipid components, which decreases the potential for acute and chronic toxicity[14].

Numerous drugs, e.g. antibiotics[4,6], plasmids[15], anti-inflammatory[16] and immuno-suppressive[9] agents, have been loaded into lipid nanoparticles for the treatment of ophthalmic disorders.

Puglia et al evaluated lipid nanocarriers for different application fields in ophthalmic treatment[17]. In another article the authors evaluated different surfactants on the technological properties and in vivo ocular tolerability of lipid nanoparticles[18]. In the current article lipid nanoparticles were described as preparation methods, characterizations and their results were discussed in recent years.

The anatomy of eye

The eye is one of the most complex organs of the body. The eyeball has spherical shape and is about 1 inch across. It houses many structures that work together to facilitate sight. The human eye is covered of layers and internal structures, each of which performs different functions[19]. Anterior segment of the eye involves of front one-third of eye that mainly includes pupil, cornea, iris, ciliary body, aqueous humor, and lens while the posterior segment consists of the back two-thirds of the eye that includes vitreous humor, retina, choroid, macula, and optic nerve (Figure 1)[20,21]. The cornea is the most anterior part of the eye, in front of the iris and pupil[22]. It is approximately 0.5 mm thick in the center and 0.7 mm thick at periphery and composed of five layers. The sclera is the hard white sheath that forms the external layer of the eyeball. It maintains the shape of the eye as an approximately globe form[23]. The conjunctiva has leakier epithelium than the cornea and its surface area is also approximately 20 times larger than the cornea[23].

Delivery routes and its challenges of ocular drug delivery

There are numerous potential routes of ocular drug delivery. The selection of the route of administration depends primarily on the target tissue. The three primary approaches of delivery of ocular drugs to the eye are topical, local ocular (ie, subconjunctival, intravitreal, retrobulbar, intracameral), and systemic delivery[24,25]. Topical application is the most popular and preferred route due to ease application, low cost, patient compliance[26]. Although it has easy availability, the eye is well protected from drugs and foreign materials by numerous effective mechanisms such as blinking, tear flow, nasolacrimal drainage, which cause quick elimination of drugs from the eye surface[27]. Therefore, topically administered treatments are rapidly drained and result in less than 5% bioavailability[28]. After instillation of the eye drops, the flow of lacrimal fluid removes instilled compounds from the eye surface. Although the lacrimal turnover rate is only about 1 μl/min the extra volume of the instilled fluid is flown to the nasolacrimal channel rapidly[23].

Intraocular (intravitreal or intraretinal) drug delivery is the most invasive route, in that it contains penetrating the eyeball and thus is not free of injection-related complications. Thus, compared with the other drug delivery routes, it reaches the highest bioavailability in posterior tissues[29,30]. However, this route causes to undesirable problems such as cataract, retinal detachment, vitreous hemorrhage, and endophthalmitis[31].

Other than topical and intravitreal routes of delivery, periocular routes such as sub-tenon and subconjunctival routes can also be used to deliver drugs to the eye[32]. Subconjunctival injections have been used to deliver drugs at increased levels to the uvea. After subconjunctival injection drug must penetrate across sclera which is more permeable than the cornea. The scleral permeability is not dependent on drug lipophilicity and shows high permeability to the large molecules[23,33].

Nanotechnology based ocular drug delivery

Various efforts have been made to improve the the drug release and absorbing rate from formulations to enhance ocular bioavailability. The development of effective drug delivery systems that can transport and deliver a drug precisely and safely to its site of action is becoming a highly important research area for pharmaceutical researchers[34]. Various efforts in ocular drug delivery have been made to improve the bioavailability and to prolong the residence time of drugs applied topically onto the eye[35]. New alternative approach is to develop a drug delivery system that would circumvent the problems associated with the conventional systems, and provide the advantages of targeted delivery of drugs for extended periods of time and be patient-friendly. The latter requisite becomes more crucial in cases where the patient has to use the drug preparation throughout his life[36]. Use of nanotechnology has been advantageous for ocular drug delivery. The use of nanotechnology-based drug delivery systems such as microemulsions, nanosuspensions, nanoparticles, solid lipid nanoparticles, niosomes, dendrimers, and liposomes has led to the solution of various solubility-related problems of poorly soluble drugs, poor permeability and short retention time[37]. In addition nanotechnology based ophthalmic formulations are one of the approaches which are currently being pursued for both anterior, as well as posterior segment drug delivery. Nanotechnology-based drug delivery is also very efficient in crossing membrane barriers, such as the blood retinal barrier in the eye[38].

Lipid nanoparticles

Nanoparticles are smaller than 1 micron and possibly as small as atomic and molecular length scales (~0.2 nm)[39]. Nanoparticles can have amorphous or crystalline form and their surfaces can act as carriers for liquid droplets or gases. They are commonly classified based on their dimensionality, morphology, composition, uniformity, and agglomeration[40]. Lipid nanoparticles made from lipids are especially attractive because of their enhanced biocompatibility imparted by the lipid. They are novel particulate drug delivery systems which have gained considerable interest since last decade[12]. During the last years, different materials have been entrapped into lipid nanoparticles, extending from lipophilic and hydrophilic molecules, including labile compounds, such as proteins and peptides[41,42,43].

Solid lipid nanoparticles (SLNs)

SLNs were developed at the beginning of the 1990s as an alternative carrier system to liposomes, emulsions and polymeric nanoparticles as a colloidal system for controlled drug delivery. SLNs consist of a solid lipid, where the drug is normally incorporated, with an average diameter below 1 µm[44,45]. The common excipients used in SLN formulation are solid lipids, emulsifiers, co-emulsifiers and water[46]. They display major advantages such as controlled release, improved bioavailability, protection of chemically labile molecules, cost effective excipients, enhanced drug incorporation and extensive application range[47]. SLNs represent an interesting alternative to traditional colloidal carriers, such as emulsions, liposomes and polymeric nanoparticles. In recent years, many hydrophobic and hydrophilic drugs such as e.g. nifedipine, diazepam, desoxycorticosterone, cyclodextrin complexes with hydrocortisone and progesterone, doxorubicin, paclitaxel, tobramycin, timolol, pilocarpine, etc. have been incorporated into SLN, and administration of SLN by different routes (parenteral, oral, ocular, etc.) has been investigated[48,49,50].

Nanostructured lipid carriers (NLCs)

NLCs are drug delivery systems composed of both solid and liquid lipids as a core matrix. NLCs disclose some advantages for drug therapy over conventional carriers, including increased solubility, the ability to enhance storage stability, improved permeability and bioavailability, reduced adverse effect, prolonged half-life, and tissue-targeted delivery[51]. On account of the physiological and/or biodegradable lipids, this carrier system also exhibits an excellent tolerability[52].

Recent studies

Several features of SLN and NLC make them interesting carriers for ophthalmic applications (Table 1). These systems are commonly applied topically to the eye. Cavalli et al. developed a SLN system of tobramycin for topical ocular drug delivery. In vivo testing has shown sustained drug release over a period of 6 h compared to short duration from equal dose of eye drops[53].

Attama et al developed lipid nanoparticles containing sodium diclofenac combining the phospholipid, with high encapsulation efficiency applying the hot high-pressure homogenization technique. Permeation of sodium diclofenac through the cornea construct was improved by surfacing nanoparticles with phospholipid, which showed the performance of this formulation for ocular application[54].

Gökçe et al developed cyclosporine A loaded SLNs using Poloxamer 188 and Tween 80 as surfactant. Corneal cytotoxicity and cellular uptake tests performed in rabbit's corneal epithelial cell lines proved that cyclosporine A loaded SLNs were harmless and improved the penetration properties across the corneal cells[9].

Araujo et al prepared triamcinolone acetonide loaded NLC with high pressure homogenization using Precirol ATO5 and squalene as solid and liquid lipids respectively, and Lutrol F68 as surfactant for ocular antiangiogenic applications. The analyses confirmed that drug was mostly entrapped into the NLC, characterized by an amorphous matrix. Moreover in vivo Draize test showed no signs of ocular toxicity[55].

In recent studies baicalin loaded SLN was prepared by emulsification/ultrasonication method. In vitro release studies indicated that the baicalin loaded SLN retained the drug entity better than the baicalin solution. In the pharmacokinetics studies, the AUC value of baicalin loaded SLN was 4.0-fold versus the baicalin solution[56].

The other researchers developed flurbiprofen loaded NLCs in order to improve the bioavailability of drug used for the prevention of the inflammation. The ideal NLC presented a suitable average size for ocular delivery (228.3 nm) with a narrow size distribution (0.156), negatively charged surface (-33.3 mV) and high entrapment efficacy (~90%). In addition they have found that developed NLCs showed sustained release. Ideal NLC formulation did not show toxicity on ocular tissues[57].

Hao et al developed chloramphenicol loaded SLNs. These SLNs were successfully prepared by a modified method of melt-emulsion ultrasonication and low temperature-solidification technique. In vitro release studies showed a burst release at the initial stage followed by a prolonged release of chloramphenicol from SLN up to 48 hours. The authors found that the chloramphenicol loaded SLN could potentially be exploited as an ocular delivery system with improved drug entrapment efficiency and controlled drug release[58].

Liu et al prepared mangiferin loaded NLC formulations for the potential treatment of cataract. The optimized mangiferin loaded NLC formulation exhibited a sustained drug release with 3 months stability and 4.31-fold increase of in vitro corneal permeation. Furthermore, in vivo studies exhibited a high tolerance in the ocular tissues and prolonged drug retention capacity on the corneal surface. Finally, pharmacokinetic study suggested a 5.69-fold increase of ocular bioavailability compared with mangiferin solution[59].

Hippalgaonkar et al developed indomethacin loaded solid lipid nanoparticles for ocular delivery. They have reported a dramatic increase in the corneal permeability of indomethacin with the SLN formulation in comparison to the indomethacin solution[60].

Zhang et al prepared genistein loaded NLC using the melt-emulsification technique in the recent ocular studies. The developed genistein loaded Eudragit RS 100 modified NLC showed extended precorneal clearance and a 1.22-fold increase in AUC compared with the bare NLC. The Eudragit RS 100 modification also significantly increased corneal penetration producing a 3.3-fold increase in apparent permeability coefficients. Draize and cytotoxicity testing confirmed that the developed NLCs were found nontoxic to corneal cells[61].

Many formulation parameters have to be considered in designing an ideal formulation. Surface charge interaction of the drug and polymer has played an important role in drug release from the polymer[62]. Bio-compatibility and mucoadhesive properties of SLNs improve their interaction with ocular surface and extend corneal residence time of the drug, with the aim of ocular drug targeting.

In the recent days to further improve precorneal residence time, the surface lipid nanoparticles were coated with chitosan. Chitosan has mucoadhesive properties due to generating molecular attraction forces by electrostatic interactions with the negative charge of the eye surface[63]. For instance, Üstündağ Okur et al developed nanostructured lipid carriers and modified with chitosan oligosaccharide lactate for topical ocular application. They have found that NLCs remained 20- 40 min on the eye surface. The longest precorneal retention time was determined with chitosan modified NLCs as 40-60 min[6].

In another recent study the authors prepared NLC based inserts by means of high shear homogenization and 0.75% chitosan oligosaccharide lactate (COL) was added for ocular ofloxacin delivery for treatment of bacterial keratitis. These NLCs were used for preparing inserts by solvent casting evaporation. The developed NLC based inserts were evaluated characterization, in vitro release, microbiological, ex vivo and in vivo studies. The pre-ocular retention time was enhanced up to 24 h and Cmax was increased almost six times in comparison with commercial in the in vivo studies[2].


Effective treatment of ocular diseases is a formidable challenge for scientists in the field because the eye is one of the most complex organs in the human body. Drug delivery to the eye is hampered by anatomical factors, including the corneal epithelium, the blood–aqueous barrier and the blood–retinal barrier. Development of new drug candidates and novel delivery techniques for treatment of ocular diseases has recently accelerated. SLN and NLC are colloidal systems still being developed for ocular administration. The technology used to produce lipid nanoparticles is feasible in the laboratory, and easily reproducible at an industrial scale. These lipid nanoparticles are possible novel drug delivery systems in drug market for ophthalmic applications.


The authors have no conflicts of interest to declare.


1Vyas SP, Paliwal R, Paliwal SR. Ocular delivery of peptides and proteins. In: Van Der Walle C, editor. Peptide and protein delivery. Academic Press; London: 2011.

2 Üstündağ-Okur N, Gökçe EH, Boybıyık DI, Eğrilmez S, Ertan G, Özer Ö. Novel nanostructured lipid carrier based inserts for controlled ocular drug delivery: Evaluation of corneal bioavailability and treatment efficacy on bacterial keratitis. Expert Opin Drug Deliv 2015; 12(11): 1-17.

3 Shen J, Wan Y, Ping Q, Xiao Y, Huang X. Mucoadhesive effect of thiolated PEG stearte and its modified NLC for ocular drug delivery. J Control Release 2009;137: 217–223.

4 Üstündağ-Okur N, Gökçe EH, Eğrilmez S, Özer Ö, Ertan G. Novel ofloxacin-loaded microemulsion formulations for ocular delivery, J Ocul Pharmacol Ther 2014; 30(4): 319-332.

5 Li N, Zhuang CY, Wang M, Sun XY, Nie SF, Pan WS. Liposome coated with low molecular weight chitosan and its potential use in ocular drug delivery. Int J Pharm 2009; 379: 131–138.

6 Üstündağ-Okur N, Gökçe EH, Boybıyık DI, Eğrilmez S, Özer Ö, Ertan G. Preparation and in vitro–in vivo evaluation of ofloxacin loaded ophthalmic nano structured lipid carriers modified with chitosan oligosaccharide lactate for the treatment of bacterial keratitis, Eur J Pharm Sci 2014; 63: 204-215.

7 Ebrahim S, Peyman GA, Lee PJ. Applications of liposomes in ophthalmology. Surv Ophthalmol 2005; 50: 167–182.

8 Ammar HO, Salama HA, Ghorab M, Mahmoud A.A. Nanoemulsionas a potential ophthalmic delivery system for dorzolamide hydrochloride. AAPS Pharm Sci Tech 2009; 10: 808–819.

9 Gökçe EH, Sandri G, Bonferoni MC, Rossi S, Ferrai F, Güneri T, Caramella C. Cyclosporine A loaded SLNs: evaluation of cellular uptake and corneal cytotoxicity. Int J Pharm 2008; 364: 76–86.

10 Souto EB, Doktorovova S, Gonzalez-Mira E, Egea MA, Garcia ML. Feasibility of lipid nanoparticles for ocular delivery of anti-inflammatory drugs, Curr Eye Res 2010; 35(7): 537–552.

11 Abhilash M. Potential applications of Nanoparticles. Int J Pharm Bio Sci 2010; 1: 1-12.

12 Shah R, Eldridge D, Palombo E, Harding I. Lipid Nanoparticles: Production, Characterization and Stability Pharmaceutical Science & Drug Development, Springer International Publishing, 2015, pp 11-22.

13 Luo YF, Chen DW, Ren LX. Zhao XL, Qin J. Solid lipid nanoparticles for enhancing vinpocetine's oral bioavailability. J Control.Release 2006; 114: 53–59.

14 Mehnert W, Mader K. Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev 2001; 47: 165–196.

15 del Pozo-Rodriguez A, Delgado D, Solinís MA, et al. Solid lipid nanoparticles for retinal gene therapy: Transfection and intracellular trafficking in RPE cells. Int J Pharm 2008; 360: 177–183.

16 Li X, Nie SF, Kong J, et al. A controlled-release ocular delivery system for ibuprofen based on nanostructured lipid carriers. Int J Pharm 2008; 363: 177–182.

17 Puglia C, Offerta A, Carbone C, Bonina F, Pignatello R, Puglisi G. Lipid nanocarriers (LNC) and their applications in ocular drug delivery. Curr Med Chem 2015; 22: 1589-1602.

18 Leonardi A, Bucolo C, Romano GL, Platania CBM, Drago F, Puglisi G, Pignatello R. Influence of different surfactants on the technological properties and in vivo ocular tolerability of lipid nanoparticles, Int J Pharm 2014; 470: 133–140.

19 Dhanapal R, Ratna JV. Ocular drug delivery system – a review, IJIDD 2012; 2: 4-15.

20 Willoughby CE, Ponzin D, Ferrari S, Lobo A, Landau K, Omidi Y. Anatomy and physiology of the human eye: effects of mucopolysaccharidoses disease on structure and function – a review. Clin Experiment Ophthalmol 2010; 38: 2–11.

21 Idrees F, Vaideanu D, Fraser S, Sowden J, Khaw P. A review of anterior segment dysgeneses. Survey Ophthal 2006; 51: 213–231.

22 Müller LJ, Marfurt CF, Kruse F, Tervo TMT. Corneal nerves: structure, contents and function. Exp Eye Res 2003; 76: 521–42.

23 Urtti A. Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv Drug Deliv Rev 2006; 58: 1131–35.

24 Gaudana R, Jwala J, Boddu SHS. Mitra AK. Recent perspectives in ocular drug delivery. Pharm Res 26, 5, 2009; 1197-1216.

25 Pratik r. Amaliyar, sunita chaudhary, in situ gel forming a novel approach for sustained ophthalmic dug delivery. IJPRBS 2014; 3(2): 502-524.

26 Lee VH, Robinson JR. Topical ocular drug delivery: recent developments and future challenges, J Ocul Pharmacol 1986; 2(1): 67-108.

27 Bucolo C, Drago F, Salomone S. Ocular drug delivery: a clue from nanotechnology, Front Pharmacol 2012; 3: 188.

28 Lee VH, Robinson JR. Topical ocular drug delivery: recent developments and future challenges. J Ocul Pharmacol 1986; 2: 67–108.

29 Kim SH, Lutz RJ, Wang NS, Robinson MR. Transport barriers in transscleral drug delivery for retinal diseases. Ophthalmic Res 2007; 39: 244–254.

30 Edelhauser HF, Rowe-Rendleman CL, Robinson MR, Dawson DG, Chader GJ, Grossniklaus HE, Rittenhouse KD, Wilson CG, Weber DA; Kuppermann BD, Csaky KG, Olsen TW, Kompella UB, Holers VM, Hageman GS; Gilger BC, Campochiaro PA, Whitcup SM, Wong WT. Ophthalmic Drug Delivery Systems for the Treatment of Retinal Diseases: Basic Research to Clinical Applications, Invest Ophthalmol Vis Sci 2010; 51: 5403-5420.

31 Jonas JB, Spandau UH, Schlichtenbrede F. Short-term complications of intravitreal injections of triamcinolone and bevacizumab. Eye (Lond) 2008; 22: 590–591.

32 Amrite AC, Edelhauser HF, Singh SR, Kompella UB. Effect of circulation on the disposition and ocular tissue distribution of 20 nm nanoparticles after periocular administration. Mol Vis 2008; 14: 150–160.

33 Pitkänen L, Ranta VP, Moilanen H, Urtti A. Permeability ofbretinal pigment epithelium: effect of permeant molecular weight and lipophilicity. Investig Ophthalmol Vis Sci 2005; 46: 641–646.

34 Sahoo SK, Dilnawaz F, Krishnakumar S. Nanotechnology in ocular drug delivery. Drug Discov Today 2008; 13(3–4): 144–151.

35 Nagarwal RC, Kant S, Singh PN, Maiti P, Pandit JK. Polymeric nanoparticulate system: A potential approach for ocular drug delivery. J Control Release 2009; 136: 2–13.

36 . Azadi HA, Rafiei P. Hydrogel nanoparticles in drug delivery. Adv Drug Deliv Rev 2008; 60: 1638–164.

37 Kayser O, Lemke A, Hernandez-Trejo. The impact of nanobiotechnology on the development of new drug delivery systems, Curr Pharm Biotechnol 2005; 6: pp. 3–5.

38 Vandervoort J, Ludwig A. Ocular drug delivery: nanomedicine applications. Nanomed 2007; 2: 11–21.

39 Mohanraj V.J, Chen Y. Nanoparticles – a review. Trop J Pharm Res 2006; 5: 561-573.

40 Buzea C, Blandino I.I.P, Robbie K. Nanomaterials and nanoparticles: sources of toxicity. Biointerphases 2007; 2(4): 17-71.

41 Severino P, Andreani T, Macedo AS, Fangueiro JF, Santana MHA, Silva AM, Souto EB. Current State-of-Art and New Trends on Lipid Nanoparticles. J Drug Deliv 2012; (2012): 1-10.

42 Yang R, Gao R, Li F, He H, Tang X. The influence of lipid characteristics on the formation, in vitro release, and in vivo absorption of protein-loaded SLN prepared by the double emulsion process. Drug Dev Ind Pharm 2011; 37: 139–148.

43 Rawat M.K, Jain A, Singh S. Studies on binary lipid matrix based solid lipid nanoparticles of repaglinide: in vitro and in vivo evaluation. J Pharm Sci 2011; 100: 2366–2378.

44 Korkmaz E, Gokce E.H, Özer Ö. Development and evaluation of coenzyme Q10 loaded solid lipid nanoparticle hydrogel for enhanced dermal delivery. Acta Pharm 2013; 63(4): 517–529.

45 Gökçe E.H, Korkmaz E, Dellera E, Sandri G, Bonferoni MC, Özer Ö. Resveratrol-loaded solid lipid nanoparticles versus nanostructured lipid carriers: evaluation of antioxidant potential for dermal applications. Int J Nanomed 2012; 7: 1841–1850.

46 Yadav N, Khatak S, Sara U.V. Solid lipid nanoparticles a review. Int J Appl Pharm 2013; 5(2): 8-18.

47 Mukherjee S, Ray S, Thakur R.S. Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J Pharm Sci 2009; 71(4): 349–358.

48 Gasco M.R. Solid lipid nanospheres from warm micro-emulsions. Pharm Technol Eur 1997; 9: 52–58.

49 Gasco M.R. Solid lipid nanoparticles for drug delivery. Pharm Technol Eur 2001; 13: 32–42.

50 Siekman B.K. Westesen Submicronized parenteral carrier systems based on solid lipid nanoparticles. Pharm Pharmacol Lett 1992; 1: 123–126.

51 Hirlekar R, Garse H, Kadam V. Solid lipid nanoparticles and nanostructured lipid carriers: a review. Curr Drug Ther 2011; 6(4): 240-250.

52 Luo Q, Zhao J, Zhang X. Weisan Pan Nanostructured lipid carrier (NLC) coated with Chitosan Oligosaccharides and its potential use in ocular drug delivery system. Int J Pharm 2011; 403(1–2): 185–191.

53 Cavalli R, Gasco MR, Chetoni P, Burgalassi S, Saettone MF. Solid lipid nanoparticles (SLN) as ocular delivery system for tobramycin. Int J Pharm 2002; 238: 241–245.

54 Attama AA, Reichl S, Muller-Goymann CC. Diclofenac sodium delivery to the eye: in vitro evaluation of novel solid lipid nanoparticle formulation using human cornea construct. Int J Pharm 2008; 355: 307-13.

55 Araújoa J, Gonzalez-Miraa E, Egeaa MA, Garciaa ML, Souto EB. Optimization and physicochemical characterization of a triamcinolone acetonide-loaded NLC for ocular antiangiogenic applications. Int J Pharm 2010; 393(1-2):167-175.

56 Liu Z, Zhang X, Wu H, Li J, Shu L, Liu R, Li L, Nan L. Preparation and evaluation of solid lipid nanoparticles of baicalin for ocular drug delivery system in vitro and in vivo, Drug Develop Ind Pharm 2010; 37(4):475-481.

57 Gonzalez-Mira E, Egea MA, Souto EB, Calpena AC, García ML. Optimizing flurbiprofen-loaded NLC by central composite factorial design for ocular delivery. Nanotechnology 2011; 22(4) 045101.

58 Hao J, Fang X, Zhou Y, Wang J, Guo F, Li F, Peng X. Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design, Int J Nanomed 2011; 6: 683–692.

59 Liu R, Liu Z, Zhang C, Zhang B. Nanostructured lipid carriers as novel ophthalmic delivery system for mangiferin: improving in vivo ocular bioavailability. J Pharm Sci 2012; 101(10): 3833-3844.

60 Hippalgaonkar K, Adelli GR, Hippalgaonkar K, Repka MA, Majumdar S. Indomethacin-loaded solid lipid nanoparticles for ocular delivery: development, characterization, and in vitro evaluation. J Ocul Pharmacol Ther 2013; 29(2): 216-228.

61 Zhang W, Li X, Ye T, Chen F, Yu S, Chen J, Yang X, Yang N, Zhang J, Liu J, Pan W, Kong J. Nanostructured lipid carrier surface modified with Eudragit RS 100 and its potential ophthalmic functions. Int J Nanomed 2014; 9(1): 4305-4315.

62 Li VH, Wood RW, Kreuter J, Harmia T, Robinson JR. Ocular drug delivery of progesterone using nanoparticles. J Microencapsul 1986; 3: 213–218.

63 Ludwig A. The use of mucoadhesive polymers in ocular drug delivery. Adv Drug Deliver Rev 2005; 57: 1595–1639.

Peer reviewer:Qianying Gao, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China; Bizhan Malaekeh-Nikouei, Associate Professor, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.


  • There are currently no refbacks.