Showing papers on "Solid lipid nanoparticle published in 2013"
TL;DR: In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles), carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles.
Abstract: Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles.
399 citations
TL;DR: In this paper, the authors developed two resveratrol nanodelivery systems based on lipid nanoparticles to enhance the oral bioavailability for further use in medicines, supplements, and nutraceuticals.
Abstract: Introduction Resveratrol is a polyphenol found in grapes and red wines. Interest in this polyphenol has increased due to its pharmacological cardio- and neuroprotective, chemopreventive, and antiaging effects, among others. Nevertheless, its pharmacokinetic properties are less favorable, since the compound has poor bioavailability, low water solubility, and is chemically unstable. To overcome these problems, we developed two novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance resveratrol's oral bioavailability for further use in medicines, supplements, and nutraceuticals. Methods and materials Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) loaded with resveratrol were successfully produced by a modified hot homogenization technique. These were completely characterized to evaluate the quality of the developed resveratrol-loaded nanoparticles. Results Cryo-scanning electron microscopy morphology studies showed spherical and uniform nanoparticles with a smooth surface. An average resveratrol entrapment efficiency of ~70% was obtained for both SLNs and NLCs. Dynamic light scattering measurements gave a Z-average of 150-250 nm, polydispersity index of ~0.2, and a highly negative zeta potential of around -30 mV with no statistically significant differences in the presence of resveratrol. These characteristics remained unchanged for at least 2 months, suggesting good stability. Differential scanning calorimetry studies confirmed the solid state of the SLNs and NLCs at both room and body temperatures. The NLCs had a less ordered crystalline structure conferred by the inclusion of the liquid lipid, since they had lower values for phase transition temperature, melting enthalpy, and the recrystallization index. The presence of resveratrol induced a disorder in the crystal structure of the nanoparticles, suggesting a favoring of its entrapment. The in vitro release studies on conditions of storage showed a negligible resveratrol release over several hours for both nanosystems and the in vitro simulation of gastrointestinal transit showed that the resveratrol remained mostly associated with the lipid nanoparticles after their incubation in digestive fluids. Conclusion Both nanodelivery systems can be considered suitable carriers for oral administration, conferring protection to the incorporated resveratrol and allowing a controlled release after uptake.
307 citations
TL;DR: This review is focused on the problems encountered in oral chemotherapy and the pharmaceutical nanotechnology solutions such as prodrugs, nanoemulsions, dendrimers, micelles, liposomes, solid lipid nanoparticles and nanoparticles of biodegradable polymers.
290 citations
TL;DR: A detailed review of novel lipid-based nanoformulations and their lymphatic delivery via different routes, as well as the in vivo and in vitro models used to study drug transport in the lymphatic system are provided.
Abstract: The delivery of drugs and bioactive compounds via the lymphatic system is complex and dependent on the physiological uniqueness of the system. The lymphatic route plays an important role in transporting extracellular fluid to maintain homeostasis and in transferring immune cells to injury sites, and is able to avoid first-pass metabolism, thus acting as a bypass route for compounds with lower bioavailability, ie, those undergoing more hepatic metabolism. The lymphatic route also provides an option for the delivery of therapeutic molecules, such as drugs to treat cancer and human immunodeficiency virus, which can travel through the lymphatic system. Lymphatic imaging is useful in evaluating disease states and treatment plans for progressive diseases of the lymph system. Novel lipid-based nanoformulations, such as solid lipid nanoparticles and nanostructured lipid carriers, have unique characteristics that make them promising candidates for lymphatic delivery. These formulations are superior to colloidal carrier systems because they have controlled release properties and provide better chemical stability for drug molecules. However, multiple factors regulate the lymphatic delivery of drugs. Prior to lymphatic uptake, lipid-based nanoformulations are required to undergo interstitial hindrance that modulates drug delivery. Therefore, uptake and distribution of lipid-based nanoformulations by the lymphatic system depends on factors such as particle size, surface charge, molecular weight, and hydrophobicity. Types of lipid and concentration of the emulsifier are also important factors affecting drug delivery via the lymphatic system. All of these factors can cause changes in intermolecular interactions between the lipid nanoparticle matrix and the incorporated drug, which in turn affects uptake of drug into the lymphatic system. Two lipid-based nanoformulations, ie, solid lipid nanoparticles and nanostructured lipid carriers, have been administered via multiple routes (subcutaneous, pulmonary, and intestinal) for targeting of the lymphatic system. This paper provides a detailed review of novel lipid-based nanoformulations and their lymphatic delivery via different routes, as well as the in vivo and in vitro models used to study drug transport in the lymphatic system. Physicochemical properties that influence lymphatic delivery as well as the advantages of lipid-based nanoformulations for lymphatic delivery are also discussed.
242 citations
TL;DR: C-SLNs with improved dispersibility and chemical stability in an aqueous system have been successfully developed and may represent a potentially useful cancer therapeutic curcumin delivery system.
223 citations
TL;DR: PEGylated solid lipid nanoparticles had advantages in enhancing the bioavailability of oral administration and demonstrated that pSLN can rapidly penetrate mucus secretions, whereas the SLN were strongly trapped by highly viscoelastic mucus barriers.
Abstract: The aim of the present study was to evaluate the potential of PEGylated solid lipid nanoparticle (pSLN) as mucus penetrating particles (MPP) for oral delivery across gastrointestinal mucus. The SLN was prepared by an aqueous solvent diffusion method, subsequently modified with PEG2000-stearic acid (PEG2000-SA) as hydrophilic groups. Surface properties, cytotoxicity, cellular uptake, and transport across Caco-2/HT29 coculture cell monolayers, intestinal absorption, and pharmacokinetics of pSLN were studied compared with that of SLN. Quantitative cellular uptake showed that the internalization of SLN and pSLN was an active transfer process, which would be restrained by several inhibitors of cell activity. Compared with SLN, the permeation ability of pSLN decreased through Caco-2 cell monolayer while it increased through a mucus-secreting Caco-2/HT29 coculture cell monolayer, which indicated that the mucus layer has a significant impact on determining the efficiency of oral nanoformulations. In addition to increasing permeation ability, the stability of the nanoparticles in simulated intestinal fluids was also increased by the PEGylation. Moreover, in vitro everted gut sac technique and the ligated intestinal loops model in vivo also demonstrated that pSLN can rapidly penetrate mucus secretions, whereas the SLN were strongly trapped by highly viscoelastic mucus barriers. The pharmacokinetic studies presented that pSLN exhibited improved absorption efficiency and prolonged blood circulation times with a 1.99-fold higher relative bioavailability compared with SLN. In conclusion, PEGylated solid lipid nanoparticles had advantages in enhancing the bioavailability of oral administration.
196 citations
TL;DR: This review deals with the challenges of conventional systems and achievements of each pharmaceutical class of novel drug delivery vehicle and provides prolonged plasma profile, enhanced and specific activity in vitro and in vivo in animal models.
Abstract: Methotrexate (MTX) is one of the most widely studied and effective therapeutics agents available to treat many solid tumors, hematologic malignancies, and autoimmune diseases such as rheumatoid arthritis; however, the poor pharmacokinetic and narrow safety margin of the drug limits the therapeutic outcomes of conventional drug delivery systems. For an improved delivery of MTX, several pathophysiological features such as angiogenesis, enhanced permeability and retention effects, acidosis, and expression of specific antigens and receptors can be used either as targets or as tools for drug delivery. There are many novel delivery systems developed to improve the pitfalls of MTX therapy ranged from polymeric conjugates such as human serum albumin, liposomes, microspheres, solid lipid nanoparticles, polymeric nanoparticles, dendrimers, polymeric micelles, in situ forming hydrogels, carrier erythrocyte, and nanotechnology-based vehicles such as carbon nanotubes, magnetic nanoparticles, and gold nanoparticles. Some are further modified with targeting ligands for active targeting purposes. Such delivery systems provide prolonged plasma profile, enhanced and specific activity in vitro and in vivo in animal models. Nevertheless, more complementary studies are needed before they can be applied in human. This review deals with the challenges of conventional systems and achievements of each pharmaceutical class of novel drug delivery vehicle.
175 citations
TL;DR: All the developed nanocarriers of TRE were found to be more biocompatible and effective than the marketed product, and these encouraging findings can guide in proper selection of topical carriers among diversity of such available carriers systems.
166 citations
TL;DR: In this paper, solid lipid nanoparticles and nanostructure lipid carriers were used to entrap hesperetin and broaden the knowledge of application of nanocarriers as the functional ingredients in food sectors.
Abstract: Solid lipid nanoparticles and nanostructure lipid carriers were used to entrap hesperetin and broaden confined knowledge of application of nanocarriers as the functional ingredients in food sectors. The produced nanocarriers using a high mechanical shear method were subjected to size and zeta potential analysis. The developed nanosize carriers had the encapsulation efficiency ranging from 39.90 to 63.08 %. Differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy were also employed to study thermal behavior, crystalline state, and chemical structure. The release behavior of hesperetin in simulated gastrointestinal conditions was investigated and kinetically modeled. The modeling results indicated that the release phenomenon is mostly governed by combination of Fickian and dissolution mechanisms. Stability of the nanocarriers, as analyzed for up to 30 days, at 6 and 25 °C in aqueous suspension, showed no detectable hesperetin leakage. Cryoprotectant effect of different compounds (i.e., glucose, sorbitol, glycerin, lactose, and sucrose) was also examined. Finally, the potential capability of nanocarriers for food fortification was studied using milk as a model food. The fortified milk samples were subjected to sensory analysis and results betokened that the developed nanocarriers did not show any significant difference with blank milk sample and could well mask the bitter taste, after taste, and obviate poor solubility of hesperetin.
156 citations
TL;DR: This review is focused on recent developments of the various PTX delivery systems such as prodrugs, micelles, liposomes, solid lipid nanoparticles, nanoparticles of biodegradable polymers, dendrimers, nanohydrogels, as well as PTX-eluting stents.
Abstract: Introduction: Paclitaxel (PTX) is one of the most effective broad-spectrum chemotherapeutic agents in the treatment of cancers. However, its clinical application has been limited due to its poor water solubility. Its current clinical administration uses the adjuvant of serious side effects and has undesired pharmacokinetics and biodistribution. There is, thus, a need for the development of alternate drug delivery systems of PTX to enhance its solubility, permeability and stability and further to promote a sustained, controlled and targeted delivery that will increase its therapeutic effects and reduce its side effects. Areas covered: This review is focused on recent developments of the various PTX delivery systems such as prodrugs, micelles, liposomes, solid lipid nanoparticles, nanoparticles of biodegradable polymers, dendrimers, nanohydrogels, as well as PTX-eluting stents. Expert opinion: Pharmaceutical nanotechnology can provide solutions to solve the problems encountered in drug formulation and drug ...
152 citations
TL;DR: This review provides an overview of the preparation and characterization technologies for SLBNs and focuses on recent advances in drug delivery usingSLBNs.
Abstract: Solid lipid-based nanoparticles (SLBNs) were developed as potential alternatives to other conventional drug delivery systems such as polymeric nanoparticles, liposomes, and emulsions. In general, SLBNs are divided into two types: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). SLNs are distinguishable from NLCs by the composition of solid particle matrix. SLBNs can be prepared by several methods including high pressure homogenization, solvent emulsification (or diffusion)-evaporation, and microemulsion technologies. Then, SLBNs can be characterized in terms of particle size distribution, surface charge, morphology, and crystallinity. SLBNs are well-tolerated and efficient carrier systems for parenteral, oral, inhalational, ocular, and dermal applications. This review provides an overview of the preparation and characterization technologies for SLBNs and focuses on recent advances in drug delivery using SLBNs.
TL;DR: Bioavailability of RL-HCL loaded SLN was nearly five times than that of pure RL- HCL, and in vitro release profiles were biphasic in nature and followed Higuchi model of release kinetics.
Abstract: Raloxifene hydrochloride (RL-HCL) is an orally selective estrogen receptor modulator (SERM) with poor bioavailability of nearly 2% due to its poor aqueous solubility and extensive first pass metabolism. In order to improve the oral bioavailability of raloxifene, raloxifene loaded solid lipid nanoparticles (SLN) have been developed using Compritol 888 ATO as lipid carrier and Pluronic F68 as surfactant. Raloxifene loaded SLN were prepared by solvent emulsification/evaporation method, and different concentrations of surfactant, and homogenization speed were taken as process variables for optimization. SLN were characterized for particle size, zeta potential, entrapment efficiency, surface morphology, and crystallinity of lipid and drug. In vitro drug release studies were performed in phosphate buffer of pH 6.8 using dialysis bag diffusion technique. Particle sizes of all the formulations were in the range of 250 to 1406 nm, and the entrapment efficiency ranges from 55 to 66%. FTIR and DSC studies indicated no interaction between drug and lipid, and the XRD spectrum showed that RL-HCL is in amorphous form in the formulation. In vitro release profiles were biphasic in nature and followed Higuchi model of release kinetics. Pharmacokinetics of raloxifene loaded solid lipid nanoparticles after oral administration to Wistar rats was studied. Bioavailability of RL-HCL loaded SLN was nearly five times than that of pure RL-HCL.
TL;DR: A solvent-free solid lipid based nanosystem has been developed and evaluated for topical delivery of quercetin and showed good physical stability for up to 8 weeks at 2-8 °C and biphasic release from the SLN formulation.
TL;DR: This review describes the types of pharmaceutical grade excipients used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches, and details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations.
Abstract: The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications.
TL;DR: The impact of carrier oil composition and physical state on the physical and chemical stability of lipid nanoparticles containing encapsulated β-carotene was investigated in this article, where the authors found that the particle particle particle d C was ≈ 20 for SLN and ≈ 12 for LLN and attributed the ability of the fat crystals within the lipid particle to promote partial coalescence and expulsion of carotenoids to the particle exterior.
TL;DR: It was concluded that solid lipid nanoparticles incorporated Carbopol gel had skin targeting ability and may serve as a promising carrier in treatment of fungal skin infections.
TL;DR: The NLC system showed the highest improvement in topical delivery of quercetin manifested by the amount of quERCetin retained in full thickness human skin, compared to a control formulation with similar composition and particle size in the micrometer range.
TL;DR: Solid lipid nanoparticles have the potential to solve the drug delivery problems with safe excipients used in its formulation and are found to be the most reliable carriers for this type of drugs due to its advantages over other carriers.
TL;DR: This is first report demonstrating a workable approach to regulate the administration of multiple injections of Noscapine using solid lipid nanoparticles, warranting further in vivo tumor regression study for superior management of brain cancer.
TL;DR: P-80-PIP-SLN has shown therapeutic effects in Alzheimer via reducing the oxidative stress and reducing the cholinergic degradation at 2 mg/kg dose equivalent.
Abstract: Background: Alzheimer is a fast growing disease with imprecise chemical treatments. Increased oxidative stress, decrease in acetylcholine concentration, and appearance of amyloidal proteins are reported in pathology of Alzheimer. Chemical drugs are effective but on the cost of detrimental side effects.Purpose: Present research is based on Preparation, characterization, behavioral and biochemical evaluation of brain targeted Piperine solid lipid nanoparticles in an experimentally induced Alzheimer’s model at a low dose of 2 mg/kg.Methods: Piperine solid lipid nanoparticles were prepared by Emulsification-Solvent Diffusion technique with polysorbate-80 coating to impart Brain specific targeting. Experimental Ibotenic acid induced Alzheimer’s, Force swimming test, superoxide dismutase, acetylcholenesterase enzymatic assays and also Histopathology of brain cortex was conducted to evaluate the Piperine therapeutic effects in Alzheimer’s Disease.Results: Piperine in solid lipid nanoformulation (2 mg/kg equivale...
TL;DR: It is suggested that SLNs can be successfully converted to physically superior NLCs, which have the potential to be developed further as ocular drug delivery systems for ACV.
Abstract: The objective of the present investigation was to improve the ocular bioavailability of acyclovir by incorporating it into solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). This required optimization of the process parameters, such as type of lipid, drug to lipid ratios, type and concentration of surfactants, and type and amount of liquid lipids used in the formulations. SLNs and NLCs were prepared by the modified hot oil in water microemuslion method. The prepared nanoparticles were evaluated for their particle size, zeta potential, entrapment efficiency, solid state characteristics, surface morphology, in vitro drug release, and permeation through excised cornea. The prepared nanoparticles were spherical and within the size range suitable for ocular drug delivery (400–777.56 nm). Incorporation of liquid oil in the structure of SLNs resulted in the formation of NLCs with high entrapment efficiency (25–91.64%) compared to SLNs (11.14%). The drug release from SLNs and NLCs was rath...
TL;DR: The findings suggested the feasibility of investigated system for intranasal administration of ropinirole hydrochloride loaded in solid lipid nanoparticles (SLNs) in the treatment of Parkinson’s disease.
Abstract: Present investigation deals with intranasal delivery of ropinirole hydrochloride (ROPI HCl), loaded in solid lipid nanoparticles (SLNs). Prime objectives of this experiment are avoidance of hepatic first pass metabolism and to improve therapeutic efficacy in the treatment of Parkinson’s disease. SLNs were fabricated by emulsification-solvent diffusion technique. A 32-factorial design approach has been employed to assess the influence of two independent variables, namely Pluronic F-68 and stearylamine concentration on particle size, ζ-potential and entrapment efficiency of prepared SLNs. Prepared samples were further evaluated for in vitro drug diffusion, ex vivo drug permeation, histopathological and stability studies. Differential scanning calorimetry analysis revealed the encapsulation of amorphous form of drug into lipid matrix, while scanning electron microscopy studies indicated the spherical shape. Fabricated SLNs had shown no severe signs of damage on integrity of nasal mucosa. Release patt...
TL;DR: SLN gel may be a promising delivery system for MLX in the treatment of inflammatory disorders because of its marked anti-inflammatory activity and excellent skin tolerability.
TL;DR: The tumor targeting and profound tumor inhibition effect of SLN-curcumin indicated its medical application on lung cancer treatment, and also provided a novel method for new anticancer agents' development.
TL;DR: This review provides an overview of pharmaceutical systems of interest in current research and strategies for their successful electron microscopic analysis, and advantages and limitations of the different methodological approaches are discussed.
TL;DR: It is suggested that LDL‐mimetic SLNs can be utilized as a multifunctional and optically traceable nanocarrier for efficient anticancer theranostics and show synergistic therapeutic effects of paclitaxel‐siRNA combination.
Abstract: Here, we report quantum dot-incorporating solid lipid nanoparticles (SLNs) for anticancer theranostics with synergistic therapeutic effects of paclitaxel-siRNA combination. The natural components of a low-density lipoprotein (LDL) are reconstituted to produce LDL-mimetic SLNs having a stable core/shell nanostructure incorporating quantum dots and paclitaxel within the lipid shell while anionic siRNA molecules are electrostatically complexed with the outer surface of SLNs. The produced SLN/siRNA complexes efficiently deliver both of paclitaxel and Bcl-2 targeted siRNA into human lung carcinoma cells and exhibit synergistic anticancer activities by triggering caspase-mediated apoptosis as determined by median effect plot analysis. Moreover, the strong fluorescence from quantum dots within SLNs enables in situ visualization of intracellular translocation of SLNs into cancer cells. Our study suggests that LDL-mimetic SLNs can be utilized as a multifunctional and optically traceable nanocarrier for efficient anticancer theranostics.
TL;DR: Hy-SLN presented a 30% increase in cell uptake and a correlated improvement of 26% in cytotoxicity, and all these advantages suggest that Hy-loaded SLN has potential for use in photodynamic therapy (PDT).
Abstract: The hydrophobicity of some photosensitizers can induce aggregation in biological systems, which consequently reduces photodynamic activity. The conjugation of photosensitizers with nanocarrier systems can potentially be used to overcome this problem. The objective of this study was to prepare and characterise hypericin-loaded solid lipid nanoparticles (Hy-SLN) for use in photodynamic therapy (PDT). SLN were prepared using the ultrasonication technique, and their physicochemical properties were characterised. The mean particle size was found to be 153 nm, with a low polydispersity index of 0.28. One of the major advantages of the SLN formulation is its high entrapment efficiency (EE%). Hy-SLN showed greater than 80% EE and a drug loading capacity of 5.22% (w/w). To determine the photodynamic efficiency of Hy before and after encapsulation in SLN, the rate constants for the photodecomposition of two (1)O2 trapping reagents, DPBF and AU, were determined. These rate constants exhibited an increase of 60% and 50% for each method, respectively, which is most likely due to an increase in the lifetime of the triplet state caused by the increase in solubility. Hy-SLN presented a 30% increase in cell uptake and a correlated improvement of 26% in cytotoxicity. Thus, all these advantages suggest that Hy-loaded SLN has potential for use in PDT.
TL;DR: Findings suggest that DHA-doxorubicin-loaded SLN is a promising alternative for the treatment of cancer, and the improved cellular uptake achieved with the drug encapsulation can be an explanation.
TL;DR: It seems that pulmonary delivery of SLNs may improve patients' compliance due to reduction of drug side effects in kidneys and elongation of drug dosing intervals due to the sustained drug release from SLNs.
Abstract: The main purpose of the present work was studying the biodistribution of amikacin solid lipid nanoparticles (SLNs) after pulmonary delivery to increase its concentration in the lungs for treatment of cystic fibrosis lung infections and also providing a new method for clinical application of amikacin. To achieve this aim, 99mTc labelled amikacin was loaded in cholesterol SLNs and after in vitro optimization, the desired SLNs and free drug were administered through pulmonary and i.v. routes to male rats and qualitative and biodistribution studies were done. Results showed that pulmonary delivery of SLNs of amikacin by microsprayer caused higher drug concentration in lungs than kidneys while i.v. administration of free drug caused reverse conditions. It seems that pulmonary delivery of SLNs may improve patients' compliance due to reduction of drug side effects in kidneys and elongation of drug dosing intervals due to the sustained drug release from SLNs.
TL;DR: Results from this study suggest that topical IN-SLNs could significantly improve ocular bioavailability of indomethacin.
Abstract: Purpose: The goal of this study was to develop and characterize indomethacin-loaded solid lipid nanoparticles (IN-SLNs; 0.1% w/v) for ocular delivery. Methods: Various lipids, homogenization pressures/cycles, Tween 80 fraction in the mixture of surfactants (Poloxamer 188 and Tween 80; total surfactant concentration at 1% w/v), and pH were investigated in the preparation of the IN-SLNs. Compritol® 888 ATO was selected as the lipid phase for the IN-SLNs, as indomethacin exhibited a highest distribution coefficient and solubility in this phase. Results: Homogenization at 15,000 psi for 6 cycles resulted in the smallest particle size. Increase in the Poloxamer 188 fraction resulted in decrease in the entrapment efficiency (EE). The mean particle size, polydispersity index, zeta-potential, and EE of the optimized formulation were 140 nm, 0.16, −21 mV, and 72.0%, respectively. IN-SLNs were physically stable post-sterilization and on storage for a period of 1 month (last timepoint tested). A dramatic in...