Hydrophilic coating of mitotane-loaded lipid nanoparticles: Preliminary studies for mucosal adhesion

The aim of the present work was to load mitotane, an effective drug for adrenocortical carcinoma treatment, in solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). The SLN and NLC were successfully prepared by high shear homogenization followed by hot high pressure homogenization. Formulations were composed of cetyl palmitate as the solid lipid for SLN, whereas for NLC PEGylated stearic acid was selected as solid lipid and medium chain triacylglycerols as the liquid lipid. Tween® 80 and Span® 85 were used as surfactants for all formulations. The particle size, zeta potential, polydispersity index (PI), encapsulation efficiency (EE), and loading capacity (LC) were evaluated. The SLN showed a mean particle size of 150?nm, PI of 0.20, and surface charge ?10 mV, and the EE and LC could reach up to 92.26% and 0.92%, respectively. The NLC were obtained with a mean particle size of 250?nm, PI of 0.30, zeta potential ?15 mV and 84.50% EE, and 0.84% LC, respectively. Hydrophilic coating of SLN with chitosan or benzalkonium chloride was effective in changing zeta potential from negative to positive values. The results suggest that mitotane was efficiently loaded in SLN and in NLC, being potential delivery systems for improving mitotane LC and controlled drug release.     

Nanostructured lipid carriers as a delivery system of biochanin A

Abstract

The aim of this study was to explore the nanostructured lipid carriers as a delivery system of biochanin A so as to supply a method to improve its bioavailability. Biochanin A–loaded nanostructured lipid carriers (BCA-NLCs) were prepared by the method of emulsion-evaporation and low temperature solidification. Pharmacokinetics was carried out in rats upon oral administration at a dose of 10?mg/kg. BCA-NLC showed spherical formulation and had mean diameter174.68?±?0.96?nm, zeta potential ?20.9?±?0.8?mv and entrapment efficiency 97.36?±?0.14%. DSC and XRD studies indicated that BCA was not in crystal state in NLC. In in vitro release study, the BCA from BCA-NLC exhibited a biphasic release pattern with burst release initially and sustained release afterwards. BCA-NLC showed higher AUC value and circulated in blood for a longer time than BCA suspension. The studies demonstrated that NLC could be a potential delivery system for BCA to improve bioavailability.     

Lipid Based nanoformulation of lycopene improves oral delivery: formulation optimization,ex vivo assessment and its efficacy against breast cancer

This study aims at developing an optimised nanostructured lipid carrier (NLC) of lycopene for efficient absorption following oral administration. The optimised formulation showed an average particle size of 121.9?±?3.66?nm, polydispersity index (PDI) 0.370?±?0.97 and zeta potential ?29.0?±?0.83?mV. Encapsulation Efficiency (% EE) and drug loading (% DL) was found to be 84.50%?±?4.38 and 9.54%?±?2.65, respectively. In vitro release studies demonstrated the burst release within 4–9?h followed by sustained release over 48?h. The IC₅₀ value of lycopene extract and optimised NLC for ABTS^+? were found to be 172.37?μg Trolox equivalent and 184.17?μg Trolox equivalent whereas, for DPPH^?, 117.76?μg Trolox equivalent and 143.08?μg Trolox equivalent respectively. Ex vivo studies and MTT assay revealed that the NLC had better permeation and cause sufficiently more cytotoxicity as compared to drug extract due to higher bioavailability and greater penetration.     

Preparation,characterization and biodistribution of nanostructured lipid carriers for parenteral delivery of bifendate

Nanostructured lipid carrier (NLC)-loaded bifendate (DDB) was prepared by melt-emulsification method to improve drug payloads and liver targeting. The particle size of the prepared formulation analysed by photon correlation spectroscopy (PCS) was 217.4?nm with a narrow polydispersity index (PI) lower than 0.2, meanwhile the loading capacity increased from 4.3% to 15.7% in comparison with DDB-loaded SLN reported in previous study. The zeta potential value was ?21.91?mV, and transmission electron microscopy studies revealed NLC of irregularly spherical shape. With respect to lipid polymorphism, a less ordered structure of NLC was confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). In addition, tissue distribution of DDB-loaded NLC and DDB solution were carried out in Kunming strain mice. In tested organs, the distribution of DDB-loaded NLC to liver was higher than that of free drug. These results support the potential applications of NLC for the delivery of DDB.     

Preparation and characteristics of monostearin nanostructured lipid carriers

Nanostuctured lipid carriers (NLC) consisted of solid lipid and liquid lipid are a new type of lipid nanoparticles, which offer the advantage of improved drug loading capacity and release properties. In this study, solvent diffusion method was employed to produce NLC. Monostearin (MS) and caprylic/capric triglycerides (CT) were chosen as the solid lipid and liquid lipid. Clobetasol propionate used as a model drug was incorporated into the NLC. The influences of preparation temperature and CT content on physicochemical properties of the NLC were characterized. As a result, monostearin solid lipid nanoparticles (without CT content, SLN) obtained at higher temperature (70 degrees C) exhibited slightly higher drug loading capacity than that of 0 degrees C (P < 0.05). In contrast, the production temperature made little effect on NLC drug loading capacity (P > 0.05). The improved drug loading capacity was observed for NLC and it enhanced with increasing the CT content in NLC. The results were explained by differential scanning calorimetry (DSC) measurement for NLC. The incorporation of CT to NLC led to crystal order disturbance and thus left more space to accommodate drug molecules. NLC displayed a good ability to reduce the drug expulsion in storage compared to SLN. The in vitro release behaviors of NLC were dependent on the production temperature and CT content. NLC obtained at 70 degrees C exhibited biphasic drug release pattern with burst release at the initial 8h and prolonged release afterwards, whereas NLC obtained at 0 degrees C showed basically sustained drug release throughout the release time. The drug release rates were increased with increasing the CT content. These results indicated that the NLC produced by solvent diffusion method could potentially be exploited as a carrier with improved drug loading capacity and controlled drug release.     

Nanostructured lipid carriers of pioglitazone for transdermal application: from experimental design to bioactivity detail

Abstract

Pioglitazone (PZ) an anti-hyperglycemic agent is used in the treatment of type 2 diabetes. The aim of this study was to design PZ-loaded nanostructured lipid carriers (NLC) to investigate the bioavailability improvement by transdermal delivery. PZ NLCs were prepared using high-pressure homogenization followed by ultrasonication. The NLCs were evaluated for particle size analysis, drug loading, ex vivo skin transport studies and in vivo bioactivity study. The prepared NLCs had a mean size of 166.05?nm and drug loading of 10.41% with flux value of 47.36?µg/cm²/h. The entrapment of PZ is >70% in the NLCs with enhancement ratio of 3.2 times. The in vivo pharmacokinetic study showed 2.17 times enhancement in bioavailability study and pharmacodynamics study showed that PZ NLC-based transdermal therapeutic system (PNLG-TTS) lowers blood sugar level in a sustained pattern for a prolonged period of time as compared to Piosys tablet (marketed). The shelf life of the optimized formulation was found to be 1.83?years. These results clearly provide a lead that above NLCs-based TTS is potential controlled release formulation for PZ and could be a promising drug delivery system for the treatment of diabetes.     

Preparation and characterization of minoxidil loaded nanostructured lipid carrier gel for effective treatment of alopecia

In the present work attempts have been made to prepare the nanostructured lipid carrier (NLC) gel, by using minoxidil, which is preferably used in case of Alopecia, i.e. baldness pattern as a effective drug. The nine different formulations of Minoxidil-NLC (NLC1–NLC9) were prepared using solid and liquid lipids with Cholesterol and Soya lecithin in different concentrations by the melt dispersion ultrasonication method. Properties of NLC1–NLC9 such as the particle size and its distribution, the scanning electron microscopy (SEM), the drug entrapment efficiency (EE), and the drug release behavior were investigated. The nanoparticulate dispersion was suitably gelled and characterized with respect to drug content, pH, spreadability, rheology, and in vitro release. Safety of the NLC-based gel was assessed using primary skin irritation studies. The formulated NLC3 was spherical in shape, with average particle size of 280 nm, zeta potential of ?42.40 mV and entrapment efficiency of 86.09%. Differential Scanning Calorimeter (DSC) measurements revealed that imperfect crystallization occurred in the inner core of the NLC particles. The drug release behavior from the NLC displayed a biphasic drug release pattern with burst release at the initial stage followed by sustained release. These results indicated that the NLC3 is a suitable carrier of minoxidil with improved drug loading capacity and controlled drug release properties. It has been observed that NLC gel produces the gel with good consistency, homogeneity, spreadability and rheological behavior. The developed NLC-based gel showed faster onset and elicited prolonged activity up to 16 h. The present study concluded that the NLC-based gel containing minoxidil dissolved in a mixture of solid lipid and liquid lipid in the nanoparticulate form helped us to attain the objective of faster onset yet prolonged action as evident from in vitro release.     

N-acetyl-L-cysteine functionalized nanostructured lipid carrier for improving oral bioavailability of curcumin: preparation,in vitro and in vivo evaluations

The application of orally administered nanoparticles in the circulation system is limited by the secretion and shedding of intestinal tract mucous layer. In order to enhance mucoadhesion and mucus penetration of curcumin (Cur)-loaded nanostructured lipid carrier (NLC) after oral administration, a new multifunctional conjugate, N-acetyl-L-cysteine-polyethylene glycol (100)-monostearate (NAPG), was synthesized. Functionalized nanocarriers (Cur-NAPG-NLC) modified by different amounts of NAPG (the amounts of NAPG were 20, 50, and 100?mg) were prepared and investigated for in vitro and in vivo behavior. Mean particle sizes of 89–141?nm with negative zeta potential (?15 to ?11?mV) and high encapsulation efficiency (EE,?>90%) possessing spherical and stable nanocarriers were observed. Sustained drug release was also observed for the NAPG-NLC. In situ intestinal perfusion studies showed that with increasing the amount of NAPG increase absorption of Cur. In vivo oral pharmacokinetic evaluation suggested that the bioavailability of Cur in rats was proportional to the degree of functionalization of NLCs with NAPG. AUC_0–t of Cur-NAPG100-NLC was improved by 499.45 and 116.89 folds as compared to that of Cur solution and unmodified Cur-NLC, respectively. In conclusion, NAPG modified NLC could be a promising drug delivery system for improving oral performance of BCS class IV drugs.     

Quality by design approach to understand the process of optimization of iloperidone nanostructured lipid carriers for oral bioavailability enhancement

Abstract

Context: The current work was carried out by exploring the principles of quality by design approach to develop an optimized nanostructured lipid carrier (NLC) formulation of poorly water soluble active iloperidone (ILO) through systematic statistical study. The potential of NLC for improving the oral bioavailability of ILO was also evaluated.

Objective: To understand the effect of formulation variables (critical parameters) on the performance characteristics (critical quality attributes) of NLC.

Materials and methods: A 3-factor, 3-level Box–Behnken factorial design was explored to predict the responses such as particle size (Y₁) and % entrapment efficiency (EE) (Y₂) when concentration of lipid (X₁), concentration of drug (X₂) and concentration of surfactant (X₃) were selected as independent variables.

Results and discussion: Particle size analysis revealed that all the batches were within the nanometer range. The % EE was found to be between 63% and 96%. In-vitro release study demonstrated sustained release profile of ILO NLC. The pharmacokinetic study in Wistar rats over the period of 24?h demonstrated 8.30-fold increase in oral bioavailability of ILO NLC as compared with ILO pure drug suspension.

Conclusion: The NLC formulation remarkably improved the oral bioavailability of ILO and demonstrated a promising perspective for oral delivery of poorly water-soluble drugs.     

Preparation and characteristics of oridonin-loaded nanostructured lipid carriers as a controlled-release delivery system

In order to improve drug entrapment efficiency and loading capacity, nanostructured lipid carriers consisting of solid lipid and liquid lipid as a new type of colloidal drug delivery system were prepared. The dispersions of oridonin-loaded solid lipid nanoparticles and nanostructured lipid carriers were successfully prepared by the emulsion-evaporation and low temperature-solidification technique using monostearin as the solid lipid, caprylic/capric triglycerides as the liquid lipid and oridonin as the model drug. Their physicochemical properties of oridonin-loaded nanostructured lipid carriers and release behaviours were investigated and compared with those of solid lipid nanoparticles. As a result, the mean particle size was ～200 nm with narrow polydispersity index lower than 0.4 for all developed formulations. Zeta potential values were in the range ?35 mV ～ ?50 mV, providing good physical stability of all formulations. The differential scanning calorimetry and X-ray diffraction analysis results demonstrated lipid nanoparticles exhibited crystal order disturbance and thus left more space to accommodate drug molecules. The improved drug entrapment efficiency and loading capacity were observed for nanostructured lipid carriers and they enhanced with increasing the caprylic/capric triglycerides content. In vitro drug release experiments exhibited biphasic drug release patterns with burst release initially and prolonged release afterwards. These results indicated that nanostructured lipid carriers could potentially be exploited as a delivery system with improved drug entrapment efficiency and controlled drug release.     

Nanostructured lipid carriers (NLCs) versus solid lipid nanoparticles (SLNs) for topical delivery of meloxicam

Abstract

Objective: The aim of this study was to develop nanostructured lipid carriers (NLCs) as well as solid lipid nanoparticles (SLNs) and evaluate their potential in the topical delivery of meloxicam (MLX).

Materials and methods: The effect of various compositional variations on their physicochemical properties was investigated. Furthermore, MLX-loaded lipid nanoparticles-based hydrogels were formulated and the gels were evaluated as vehicles for topical application.

Results and discussion: The results showed that NLC and SLN dispersions had spherical shapes with an average size between 215 and 430?nm. High entrapment efficiency was obtained ranging from 61.94 to 90.38% with negatively charged zeta potential in the range of ?19.1 to ?25.7?mV. The release profiles of all formulations exhibited sustained release characteristics over 48?h and the release rates increased as the amount of liquid lipid in lipid core increased. Finally, Precirol NLC with 50% Miglyol® 812 and its corresponding SLN were incorporated in hydrogels. The gels showed adequate pH, non-Newtonian flow with shear-thinning behavior and controlled release profiles. The biological evaluation revealed that MLX-loaded NLC gel showed more pronounced effect compared to MLX-loaded SLN gel.

Conclusion: It can be concluded that lipid nanoparticles represent promising particulate carriers for topical application.     

Development of a new delivery system consisting in “drug - in cyclodextrin - in nanostructured lipid carriers” for ketoprofen topical delivery

A new delivery system based on drug cyclodextrin (Cd) complexation and loading into nanostructured lipid carriers (NLC) has been developed to improve ketoprofen therapeutic efficacy. The proposed strategy exploits both the solubilizing and stabilizing properties of Cds and the prolonged release, high tolerability and percutaneous absorption enhancer properties of NLC. Two different polymeric Cds, i.e. β-Cd-epichlorohydrin polymer (EPI-βCd) and carboxymethylathed-β-Cd-epichlorohydrin polymer (EPI-CMβCd) were tested and two different techniques to obtain solid ketoprofen-polymeric Cd complexes (i.e. co-grinding and co-lyophilization) were compared, to investigate the influence of the preparation method on the physicochemical properties of the end product. EPI-βCd was more effective than EPI-CMβCd in enhancing the solubility and dissolution properties of ketoprofen. Co-grinding in dry conditions was the best preparation technique of solid drug-Cd systems, allowing obtainment of homogeneous amorphous particles of nanometric range. NLC consisting in a mixture of Compritol® 888 ATO (glyceryl behenate) and Labrafac Lipophile were obtained by ultrasonication. Both empty and loaded NLC were suitably characterized for particle size, pH, entrapment efficiency and drug release behavior. The best (drug-Cd)-loaded NLC system, formulated into a xanthan hydrogel, exhibited drug permeation properties clearly better than those of the plain drug suspension or the plain drug-loaded NLC, in virtue of the simultaneous exploitation of the solubilizing effect of cyclodextrin and the penetration enhancer properties of NLC.     

Improved pharmacokinetics and antihyperlipidemic efficacy of rosuvastatin-loaded nanostructured lipid carriers

In the present study, rosuvastatin calcium-loaded nanostructured lipid carriers were developed and optimized for improved efficacy. The ROS-Ca-loaded NLC was prepared using melt emulsification ultrasonication technique and optimized by Box–Behnken statistical design. The optimized NLC composed of glyceryl monostearate (solid lipid) and capmul MCM EP (liquid lipid) as lipid phase (3% w/v), poloxamer 188 (1%) and tween 80 (1%) as surfactant. The mean particle size, polydispersity index (PDI), zeta potential (ζ) and entrapment efficiency (%) of optimized NLC formulation was observed to be 150.3?±?4.67?nm, 0.175?±?0.022, ?32.9?±?1.36?mV and 84.95?±?5.63%, respectively. NLC formulation showed better in vitro release in simulated intestinal fluid (pH 6.8) than API suspension. Confocal laser scanning showed deeper permeation of formulation across rat intestine compared to rhodamine B dye solution. Pharmacokinetic study on female albino Wistar rats showed 5.4-fold increase in relative bioavailability with NLC compared to API suspension. Optimized NLC formulation also showed significant (p?<?0.01) lipid lowering effect in hyperlipidemic rats. Therefore, NLC represents a great potential for improved efficacy of ROS-Ca after oral administration.     

Cyproterone acetate-loaded nanostructured lipid carriers: effect of particle size on skin penetration and follicular targeting

Cyproterone acetate (CPA) is used to treat various skin disorders such as acne, hirsutism, and alopecia. Due to the limited skin penetration of CPA, nanostructured lipid carriers (NLCs) with different size ranges were considered in this study in order to enhance skin penetration and to target hair follicles. Drug loading, drug release and morphological assessment were evaluated for each targeted size (100, 300, and 600?nm). Ex vivo skin penetration was also investigated using Franz diffusion cells. Finally, in vivo follicular targeting was evaluated using rhodamine B-loaded micro and nanoparticles. Results revealed that 60–85% of drug was slowly released from lipid nanoparticles within 72?h. CPA-NLC with average diameter of 600?nm had better penetration and deposition in dermis-epidermis layer, also CPA-NLC 100 and 300?nm significantly increased drug penetration in dermis-epidermis in comparison to free CPA. Follicular targeting results revealed that NLC 300?nm had the best accumulation capacity in hair follicles. CPA-NLC with average diameter of 300?nm could be a promising topical novel drug delivery system for specific targeting of hair follicles and sebaceous glands to treat androgenic skin disorders such as acne, hirsutism, and alopecia.     

SLN and NLC for topical delivery of ketoconazole

The clinical use of ketoconazole has been related to some adverse effects in healthy adults, specially local reactions, such as severe irritation, pruritus and stinging. The purpose of the present work is the assessment of ketoconazole stability in aqueous SLN and NLC dispersions, as well as the physicochemical stability of these lipid nanoparticles, which might be useful for targeting this drug into topical route, minimizing the adverse side effects and providing a controlled release. Lipid particles were prepared using Compritol®888 ATO as solid lipid. The natural antioxidant α-tocopherol was selected as liquid lipid compound for the preparation of NLC. Ketoconazole loading capacity was identical for both SLN and NLC systems (5% of particle mass). SLN were physically stable as suspensions during 3 months of storage, but the SLN matrix was not able to protect the chemically labile ketoconazole against degradation under light exposure. In contrast, the NLC were able to stabilize the drug, but the aqueous NLC dispersion showed size increase during storage. Potential topical formulations are light-protected packaged SLN or NLC physically stabilized in a gel formulation.     

PLGA nanoparticles for the oral delivery of nuciferine: preparation,physicochemical characterization and in vitro/in vivo studies

This article reports a promising approach to enhance the oral delivery of nuciferine (NUC), improve its aqueous solubility and bioavailability, and allow its controlled release as well as inhibiting lipid accumulation. NUC-loaded poly lactic-co-glycolic acid nanoparticles (NUC-PLGA-NPs) were prepared according to a solid/oil/water (s/o/w) emulsion technique due to the water-insolubility of NUC. PLGA exhibited excellent loading capacity for NUC with adjustable dosing ratios. The drug loading and encapsulation efficiency of optimized formulation were 8.89?±?0.71 and 88.54?±?7.08%, respectively. NUC-PLGA-NPs exhibited a spherical morphology with average size of 150.83?±?5.72?nm and negative charge of ?22.73?±?1.63?mV, which are suitable for oral administration. A sustained NUC released from NUC-PLGA-NPs with an initial exponential release owing to the surface associated drug followed by a slower release of NUC, which was entrapped in the core. In addition, ～77?±?6.67% was released in simulating intestinal juice, while only about 45.95?±?5.2% in simulating gastric juice. NUC-PLGA-NPs are more efficient against oleic acid (OA)-induced hepatic steatosis in HepG₂ cells when compared to naked NUC (n-NUC, *p < 0.05). The oral bioavailability of NUC-PLGA-NPs group was significantly higher (**p < 0.01) and a significantly decreased serum levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), as well as a higher concentration of high-density lipoprotein cholesterol (HDL-C) was observed, compared with that of n-NUC treated group. These findings suggest that NUC-PLGA-NPs hold great promise for sustained and controlled drug delivery with improved bioavailability to alleviating lipogenesis.     

Nimodipine loaded lipid nanospheres prepared by solvent diffusion method in a drug saturated aqueous system

To overcome the disadvantages such as lower drug entrapment efficiency (EE) of lipid nanospheres prepared by conventional solvent diffusion method, a solvent diffusion method in drug saturated aqueous system was developed. Nimodipine was used as a model drug to incorporate into lipid nanospheres. The monostearin (MS) solid lipid nanoparticles (SLN) produced by conventional method under different production temperature only showed 24.40-30.21wt% EE, and relatively higher EE was achieved when the production temperature was 0 degrees C. The EE could be enhanced by the incorporation of liquid lipid (caprylic/capric triglycerides, CT) into SLN and the employing of drug saturated dispersion medium. The nanostructured lipid carrier (NLC) with higher CT content indicated the highest EE as the drug saturated aqueous solution was used as dispersion medium. The differential scanning calorimetry (DSC) results demonstrated the present method could improve the drug encapsulation into lipid nanospheres. In vitro drug release experiments indicated the present preparation method could delay the drug release rate from lipid nanospheres, and the drug release rate could adjust by the CT content in lipid nanospheres. The highest drug loading (DL) was reached up to 4.22wt% when 8wt% drug was charged in the preparation of lipid nanospheres.     

Which one performs better for targeted lung cancer combination therapy: pre- or post-bombesin-decorated nanostructured lipid carriers?

Abstract

Purpose: The co-delivery of gene and drugs has the potential to treat cancer. The aim of this study was to compare post-bombesin decorated nanostructured lipid carriers (NLC) carrying both doxorubicin (DOX) and DNA with pre-bombesin decorated NLC for lung cancer therapy.

Methods: Post-bombesin decorated NLC were prepared by two steps. First, DOX and DNA-loaded NLC (DOX-DNA-NLC) was prepared. Second, Bombesin-NH₂ (BN-NH₂) was added into DOX-DNA-NLC to react with stearic acid-polyethylene glycol-COOH (SA-PEG-COOH) loaded in NLC. Pre-bombesin decorated NLC were prepared by two steps. First, Bombesin (BN)-conjugated ligands were synthesized. Second, DOX and DNA were loaded into BN decorated NLC. Their average size, zeta potential, drug and gene loading were evaluated. NCl-H460 human non-small lung cancer cells (NCl-H460 cells) were used for the testing of in vitro transfection efficiency and in vitro cytotoxicity. In vivo transfection efficiency and anti-tumor effect of NLC were evaluated on mice bearing NCl-H460 cells model.

Results: Post-bombesin decorated NLC has a particle size of 128?nm, DOX encapsulation efficiency (EE) of 85% and DNA EE of 91%. Pre-bombesin decorated NLC has a particle size of 101?nm, DOX EE of 86% and DNA EE of 92%. Post-bombesin decorated NLC displayed more stable and remarkably higher transfection efficiency and better anti-tumor ability than pre-bombesin decorated NLC both in vitro and in vivo.

Conclusion: Post-bombesin decorated NLC could function as better carriers to improve the cell targeting and nuclear targeting ability. The resulting nanomedicine could be a promising active targeting drug/gene therapeutic system for lung cancer therapy.     

Nanostructured lipid carriers system: Recent advances in drug delivery

Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier.     

Nanostructured lipid carriers as novel ophthalmic delivery system for mangiferin: Improving in vivo ocular bioavailability

The aim of this study was to develop a novel nanostructured lipid carriers (NLCs) system to improve ocular bioavailability of mangiferin (MGN) for the potential treatment of cataract. The physicochemical properties of MGN‐loaded NLC (MGN‐NLC) formulation were characterized by particle size, polydispersity index, zeta potential, entrapment efficiency, drug loading, morphological property, and crystalline state. in vitro characteristics were investigated by drug release from NLC system, physical stability, and corneal permeation through excised rabbit cornea. Moreover, in vivo ocular tolerability was assessed by a modified Draize test and histological microscopy. Preocular retention capability was evaluated by slit‐lamp observation. Pharmacokinetic study in the aqueous humor was performed by microdialysis technique. Transmission electron microscopy depicted spherical and uniform morphology. Differential scanning calorimetry and X‐ray diffractometry displayed imperfect crystalline lattice. The optimized MGN‐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 MGN solution (MGN‐SOL). Therefore, NLC system is a promising approach for ocular delivery of MGN. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3833–3844, 2012