Lipid Nanoparticles For Oral Delivery Research Articles

Ranolazine loaded solid lipid nanoparticles for oral delivery: Characterization, pharmacokinetic and pharmacodynamic evaluation

Ranolazine loaded solid lipid nanoparticles for oral delivery: Characterization, pharmacokinetic and pharmacodynamic evaluation

Improved uptake and bioavailability of cinnamaldehyde via solid lipid nanoparticles for oral delivery

Objective The purpose of this experiment was to explore the effect of Solid lipid nanoparticles (SLNs) on improving the oral absorption and bioavailability of cinnamaldehyde (CA). Methods CA-SLNs were prepared by high-pressure homogenization and characterized by particle size, entrapment efficiency, and morphology, thermal behavior and attenuated total reflection Fourier transform infrared (ATR-FTIR). In vitro characteristics of release, stability experiments, cytotoxicity, uptake and transport across Caco-2 cell monolayer of CA-SLNs were studied as well. In addition, CA-SLNs underwent pharmacokinetic and gastrointestinal mucosal irritation studies in rats. Results CA-SLNs exhibited a spherical shape with a particle size of 44.57 ± 0.27 nm, zeta potential of −27.66 ± 1.9 mV and entrapment efficiency of 83.63% ± 2.16%. Differential scanning calorimetry (DSC) and ATR-FTIR confirmed that CA was well encapsulated. In vitro release of CA-SLNs displayed that most of the drug (90.77% ± 5%) was released in the phosphate buffer, and only a small amount of drug (18.55% ± 5%) was released in the HCl buffer. CA-SLNs were taken up by an energy-dependent, endocytic mechanism mediated by caveolae mediated endocytosis across Caco-2 cells. The CA permeation through Caco-2 cell was facilitated by CA-SLNs. The outcome of the gastrointestinal irritation test demonstrated that CA-SLNs had no irritation to the rats’ intestines. Compared with CA dispersions, incorporation of SLNs increased the oral bioavailability of CA more than 1.69-fold. Conclusions It was concluded that CA-SLNs improved the absorption across Caco-2 cell model and improved the oral administration bioavailability of CA in rats.

Silymarin loaded solid lipid nanoparticles for oral delivery: Development, characterization and cytotoxic effect on breast cancer cells

The current study aimed to develop a silymarin (SM) loaded solid lipid nanoparticles (SLNs). Further, silymarin loaded solid lipid nanoparticles (SM-SLNs) were characterized for different quality parameters. The SLNs were prepared by temperature modulated solidification technique. The glyceryl monostearate (GMS) was selected as lipid, tween 80 as surfactant and mannitol as cryoprotectant. The SM-SLNs were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), thermal behavior, and crystallinity. Further, the formulation was elucidated by MTT assay for cytotoxicity assessment. The particle size and PDI of the optimized formulation was found to be 178.6 ± 4.32 nm and 0.146, respectively. ZP (-36.4 mV) with a negative surface charge confirmed the physical stability of SLNs. Differential scanning calorimetry (DSC), X-ray diffraction (XRD) confirmed the transformation of lipid into SLNs through polymorphic transition of lipid crystallinity from β'-modification to α-modification and conversion of crystallinity of drug to amorphous state. The optimized formulation had an EE of 79.86%. The in-vitro drug release depicted a burst release for 1 h followed by fast release for 6 h and then sustained release over a duration of 24 h. SM-SLNs significantly reduced the growth of MCF-7 cells compared to silymarin. SM-SLNs exhibited small size in nanometer with narrow distribution, physically stable, and high entrapment efficiency. The developed nanoformulation could be used as a suitable drug delivery system for silymarin that has low water solubility, and a promising candidate for development of effective formulation in cancer therapy.

Preparation, Characterization and Optimization of Irbesartan Loaded Solid Lipid Nanoparticles for Oral Delivery

The purpose of this study was to develop and evaluate irbesartan (IS) loaded solid lipid nanoparticles (SLNs; IS-SLNs) that might enhance the oral bioavailability of IS. IS, an angiotensin-receptor antagonist, used to treat hypertension. However, poor aqueous solubility and poor oral bioavailability has limited therapeutic applications of IS. Components of the SLNs include either of trimyristin/tripalmitin/tristearin/trilaurate/stearic acid/beeswax, and surfactants (Poloxamer 188 and soylecithin). The IS-SLNs were prepared by hot homogenization followed by ultrasonication method and evaluated for particle size, poly dispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), drug content and in vitro drug release. The physical stability of optimized formulation was studied at refrigerated and room temperature for two months. The optimized IS-SLN formulation (F4) had a mean diameter of about 217.6±3.62 nm, PDI of 0.163±0.032, ZP of -28.5±4.12, assay of 99.8±0.51 and EE of 93.68±2.47%. The formulation showed sustained drug release compared with control formulation over 24 h. Optimized formulation was found to be stable over two months. IS-SLN showed nearly spherical in shape using and converted to amorphous form by DSC. Thus, the results conclusively demonstrated SLNs could be considered as an alternative delivery system for the oral bioavailability enhancement of IS.

Zotepine loaded lipid nanoparticles for oral delivery: development, characterization, and in vivo pharmacokinetic studies

BackgroundThe purpose of this work was to prepare and evaluate the zotepine (ZT) loaded solid lipid nanoparticles (SLNs) that might improve the oral bioavailability. ZT is an anti-psychotic drug used for the treatment of schizophrenia. Currently, it is available as parenteral and oral dosage form. But, ZT has a poor oral bioavailability of about 7–13% due to limited aqueous solubility and first-pass effect. ZT-SLNs were developed using homogenization method and characterized for optimal system based on physicochemical characteristics and in vitro release. The optimized ZT-SLNs were evaluated for permeation through rat intestine using evert sac method. The crystalline nature of the ZT-SLNs was studied using DSC and XRD analysis. Surface morphology studies were conducted using SEM. Physical stability of the optimized ZT-SLN was evaluated at refrigerator and room temperature over 2 months. Further, pharmacokinetic (PK) studies of ZT-SLN were conducted in male Wistar rats, in comparison with ZT coarse suspension (ZT-CS), in vivo.ResultsAmong all the developed ZT-SLN formulations, optimized formulation (F1) showed Z-avg, PDI, and ZP of 104.3 ± 1.6 nm, 0.17 ± 0.01, and − 30.5 ± 2.5 mV, respectively. In vitro release and permeation studies exhibited 82.9 ± 1.6% of drug release and 19.6 ± 2.1% of percentage drug permeation over 48 h and 120 min, respectively. DSC and XRD studies revealed the conversion of ZT to amorphous form. SEM studies showed spherical shape with improved PDI of ZT-SLN formulation. PK studies showed a significant (p < 0.05) improvement in AUC of about 1.3-fold, in comparison with ZT-CS in Wistar rats.ConclusionTherefore, the results concluded that SLNs could be considered as a new alternative delivery system for the enhancement of oral bioavailability of ZT.

Pharmacodynamic, pharmacokinetic and physical characterization of cilnidipine loaded solid lipid nanoparticles for oral delivery optimized using the principles of design of experiments

Cilnidipine (CND), an anti-hypertensive drug, is known to have low oral bioavailability due to its poor aqueous solubility, low dissolution rate and high gut wall metabolism. In the present study, CND loaded compritol based nanoparticles (CND-CMP-NPs) were prepared by emulsification-solvent evaporation method applying the concepts of design of experiments. Critical factors affecting particle size and loading efficiency (LE%) were assessed by hybrid design approach, comprising of Mini Run Resolution IV design followed by Box–Behnken design. Particle size, PDI, zeta potential and LE% of optimized formulations of CND-CMP-NPs were 207.1 ± 2.9 nm, 0.27 ± 0.1, −22.2 ± 1.9 mV and 15.9 ± 1.3% respectively. No significant changes were observed in physical stability of NPs when stored at 25 °C/60% RH over a period of three months. Pharmacokinetic studies revealed that Fabs of CND-CMP-NPs (0.66) was significantly higher than the free CND (0.27). The Cmax and AUC0–∞ of CND-CMP-NPs (572.4 ± 25.3 ng/mL and 5588.6 ± 229.5 ng/mL × h) were significantly higher (Pcal < 0.0001) as compared to free CND (363.6 ± 23.5 ng/mL and 2316.1 ± 163.6 ng/mL × h). MRT of CND-CMP-NPs (9.8 ± 0.9 h) was significantly higher (Pcal < 0.0001) as compared to free CND (5.7 ± 0.5 h). Pharmacodynamic studies showed a maximum of 38% decrease in systolic blood pressure with more than 20% drop in systolic blood pressure sustained for a total duration of 64 h in the case of CND-CMP-NPs as compared to free CND. CND-CMP-NPs not only provide higher and sustained plasma levels of CND but also higher and sustained antihypertensive therapy as compared to free CND.

Anti-angiogenic activity of uncoated- and N,O-carboxymethyl-chitosan surface modified-Gelucire® 50/13 based solid lipid nanoparticles for oral delivery of curcumin

The co-administration of anti-tumor and anti-angiogenesis agents represents a well-established strategy for cancer treatment. However, the clinical use of this “combined therapy” approach showed several limitations probably due to the inability of most angiogenic inhibitors to target tumor vessels. Herein, we evaluated the in vitro angiogenesis effects of N,O-carboxymethyl chitosan (N,O-CMCS) surface modified curcumin (CUR)-loaded solid lipid nanoparticles (SLN) intended for CUR oral administration. For this purpose, SLN formulations based on Gelucire® 50/13 were prepared and characterized for their physicochemical properties. From stability tests such SLN resulted useful to protect CUR from oxidative and hydrolytic degradation for a long period at 4 °C. Moreover, N,O-CMCS-c-CUR SLN (F4) displayed enhanced cytocompatibility with Caco-2 cells. Data from angiogenesis studies showed that the CUR-unloaded and surface unmodified SLN (b-SLN, F1) possess anti-angiogenic activity and, moreover, due to the features of the coating polysaccharide, F4 may constitute an anti-angiogenic delivery platform for CUR oral delivery and such delivery system seems promising in vascular angiogenesis inhibition.

Comparative study of nisoldipine-loaded nanostructured lipid carriers and solid lipid nanoparticles for oral delivery: preparation, characterization, permeation and pharmacokinetic evaluation

Nisoldipine (ND) has low oral bioavailability (5%) due to first-pass metabolism. Previously, solid lipid nanoparticles (SLNs) of ND were reported. In this study, nanostructured lipid carriers (NLCs) of ND are developed to enhance the oral bioavailability. ND-NLCs were prepared using hot homogenization-ultrasonication method, using oleic acid and trimyristate as liquid lipid and solid lipid, respectively. Prepared NLCs are evaluated for an optimal system using measuring size, zeta potential, entrapment efficiency, in-vitro release and in-situ absorption studies. Further, in vivo pharmacokinetic (PK) studies of NLC were conducted in rats comparison with SLN and suspension as controls. Size, ZP and EE of optimized NLCs were found to be 110.4 ± 2.95 nm, –29.4 ± 2.05 mV and 97.07 ± 2.27%, respectively. Drug loaded into NLCs was converted to amorphous form revealed by differential scanning calorimeter (DSC) and X-ray diffractometry (XRD) technique and nearly spherical in shape by scanning electron microscopy (SEM) studies. Drug release and absorption of ND were prolonged from ND-NLCs and ND-SLNs. From the PK results, NLCs showed 2.46 and 1.09-folds improvement in oral bioavailability of ND compared with suspension and SLNs formulations, respectively. Taken together, the NLCs and SLNs are used as carriers for the enhancement of oral bioavailability of the ND.

Development of Houttuynia cordata Extract-Loaded Solid Lipid Nanoparticles for Oral Delivery: High Drug Loading Efficiency and Controlled Release

Houttuynia cordata (H. cordata) has been used for diuresis and detoxification in folk medicine as well as a herbal medicine with antiviral and antibacterial activities. H. cordata extract-loaded solid lipid nanoparticles (H-SLNs) were prepared with various concentration of poloxamer 188 or poloxamer 407 by a hot homogenization and ultrasonication method. H-SLNs dispersion was freeze-dried with or without trehalose as a cryoprotectant. The physicochemical characteristics of H-SLNs were evaluated by dynamic laser scattering (DLS), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). Additionally, the in vitro release and in vitro cytotoxicity of H-SLNs were measured. Encapsulation efficiencies of H-SLNs (as quercitrin) were 92.9–95.9%. The SEM images of H-SLNs showed that H-SLNs have a spherical morphology. DSC and FT-IR showed that there were no interactions between ingredients. The increased extent of particle size of freeze-dried H-SLNs with trehalose was significantly lower than that of H-SLNs without trehalose. H-SLNs provided sustained release of quercitrin from H. cordata extracts. Cell viability of Caco-2 cells was over 70% according to the concentration of various formulation. Therefore, it was suggested that SLNs could be good carrier for administering H. cordata extracts.

Preparation of lipid nanoparticles with high loading capacity and exceptional gastrointestinal stability for potential oral delivery applications

Exploitation of lipid nanoparticles for oral delivery of nutrients and drugs is limited by their poor stability under gastrointestinal tract and low loading capacity, unless a high concentration of synthetic surfactants is formulated. The main objective of present study is to design a series of new formulations for solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) that are suitable for potential oral delivery applications, using natural biopolymers, i.e. sodium caseinate (NaCas) as emulsifier and pectin as coating, with minimal addition of a synthetic surfactant, Tween 80. Effects of pectin coating, concentration of Tween 80, thermal treatment (80°C for 30min), as well as two chemical cross-linkers on the particulate characteristics, stability, encapsulation efficiency, controlled release and drying feasibility were comprehensively investigated. The intermolecular interactions and cross-linking reactions were studied using Fourier transform infrared spectroscopy. Tween 80 at 0.15% (w/v) together with 0.15% (w/v) NaCas was proved effective to obtain stable cross-linked pectin-coated SLN (PSLN) under 200nm with high loading capacity for curcumin, while NLC prepared under the same condition failed to pass storage stability test. The 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) cross-linked PSLN exhibited superior characteristics than glutaradehyde (GA) cross-linked PSLN, especially for the stability and controlled release under simulated gastrointestinal conditions, with curcumin studied as a model compound. The feasibility of both nano spray drying and freeze-drying technologies were both investigated to transform of colloidal lipid nanoparticles into dry powders. Our results demonstrated a novel strategy to prepare small and homogenous SLN with exceptional GI stability and high loading capacity as a potential oral delivery system.

Self-Assembled Lipid Nanoparticles for Oral Delivery of Heparin-Coated Iron Oxide Nanoparticles for Theranostic Purposes.

Recently, solid lipid nanoparticles (SLNs) have attracted increasing attention owing to their potential as an oral delivery system, promoting intestinal absorption in the lymphatic circulation which plays a role in disseminating metastatic cancer cells and infectious agents throughout the body. SLN features can be exploited for the oral delivery of theranostics. Therefore, the aim of this work was to design and characterise self-assembled lipid nanoparticles (SALNs) to encapsulate and stabilise iron oxide nanoparticles non-covalently coated with heparin (Fe@hepa) as a model of a theranostic tool. SALNs were characterised for physico-chemical properties (particle size, surface charge, encapsulation efficiency, in vitro stability, and heparin leakage), as well as in vitro cytotoxicity by methyl thiazole tetrazolium (MTT) assay and cell internalisation in CaCo-2, a cell line model used as an indirect indication of intestinal lymphatic absorption. SALNs of about 180 nm, which are stable in suspension and have a high encapsulation efficiency (>90%) were obtained. SALNs were able to stabilise the heparin coating of Fe@hepa, which are typically unstable in physiological environments. Moreover, SALNs–Fe@hepa showed no cytotoxicity, although their ability to be internalised into CaCo-2 cells was highlighted by confocal microscopy analysis. Therefore, the results indicated that SALNs can be considered as a promising tool to orally deliver theranostic Fe@hepa into the lymphatic circulation, although further in vivo studies are needed to comprehend further potential applications.

Preparation, characterization, and in vivo study of rhein solid lipid nanoparticles for oral delivery.

In this study, rhein-SLNs were successfully produced by hot homogenization followed by ultrasonication. Precirol ATO5 in which rhein exhibited higher partition coefficient was selected for preparation of SLNs. In the dynamic light scattering, the rhein-SLNs showed a smaller size with a mean value of 120.8±7.9nm and with zeta potential of -16.9±2.3mV. SLNs exhibited a good stability during the period of 2months. The SLNs indicated faster drug release with a burst release within 2hr and followed by a sustained release with a biphasic drug-release pattern. Comparing with the same concentration (free drug), the cellular cytotoxicity of rhein-loaded SLNs increased significantly at the same incubation condition. In vivo, the AUC0-t of rhein in the form of SLNs was significantly increased and was 2.06-fold that of suspensions group. The results showed an increased oral absorption and improved the oral bioavailability of rhein by the formulation of SLNs.

Surface modification of solid lipid nanoparticles for oral delivery of curcumin: Improvement of bioavailability through enhanced cellular uptake, and lymphatic uptake

Curcumin has been reported to exhibit potent anticancer effects. However, poor solubility, bioavailability and stability of curcumin limit its in vivo efficacy for the cancer treatment. Solid lipid nanoparticles (SLN) are a promising delivery system for the enhancement of bioavailability of hydrophobic drugs. However, burst release of drug from SLN in acidic environment limits its usage as oral delivery system. Hence, we prepared N-carboxymethyl chitosan (NCC) coated curcumin-loaded SLN (NCC-SLN) to inhibit the rapid release of curcumin in acidic environment and enhance the bioavailability. The NCC-SLN exhibited suppressed burst release in simulated gastric fluid while sustained release was observed in simulated intestinal fluid. Furthermore, NCC-SLN exhibited increased cytotoxicity and cellular uptake on MCF-7 cells. The lymphatic uptake and oral bioavailability of NCC-SLN were found to be 6.3-fold and 9.5-fold higher than that of curcumin solution, respectively. These results suggest that NCC-SLN could be an efficient oral delivery system for curcumin.

Lacidipine Loaded Solid Lipid Nanoparticles for Oral Delivery: Preparation, Characterization and In vivo Evaluation

&#x0D; The objective of this study was to develop and evaluate lacidipine (LD) loaded solid lipid nanoparticles (LD-SLNs) for improving the oral bioavailability. LD-SLNs were prepared in two steps. First step was hot homogenization and next by ultrasonication method, using triglycerides (tripalmitin and tristearin), monoglyceride and surfactants (Poloxamer 188 and egg lecithin E80). The prepared LD-SLNs were characterized for particle size, PDI, zeta potential, drug content, entrapment efficiency (EE %). In vitro drug release studies using a dialysis bag method in 0.1N HCl and pH 6.8 phosphate buffer were conducted. In addition, long-term physical stability of the optimized SLNs was investigated at refrigerated and room temperature for 60 days. FTIR and DSC studies revealed that no interaction between the drug and lipids. LD-SLNs prepared with Dynasan-116 (F3), having the size of 141.86nm, PDI of 0.293, ZP of -22.3 m with 94.75% of EE was optimized and was stable for 60days. Scanning electron microscopic studies showed nearly spherical shaped particles. Further, pharmacokinetic studies were conducted in wistar rats. The relative bioavailability of LD in SLNs was 2.03 times when compared with that of the LD suspension. The results are indicative of SLNs as suitable lipid based carrier system for improving the oral bioavailability of LD.

Development and evaluation of insulin-loaded cationic solid lipid nanoparticles for oral delivery

Cationic solid lipid nanoparticles (cSLN) loaded with insulin for oral delivery were prepared by the so-called water-in-oil-in-water double emulsion technique. The lipid matrix was composed of glyceryl palmitostearate and 1,2-dioleoyl-3-trimethylammonium-propane as a cationic lipid. Depending on the formulation, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] was incorporated to decrease the adsorption of insulin onto the surface of the nanoparticles. This aimed to achieve a positive zeta potential to obtain bioadhesion properties. The cSLN were characterized by a Z-average lower than 300 nm and by a zeta potential higher than 33 mV. The loading efficiency was ranged between 30% and 42%. It was shown that all the nanoparticles developed were able to fix solubilized mucin, which was used to evaluate bioadhesion properties. The cSLN also allowed the encapsulated insulin to be protected from the enzymatic activity of both pepsin and trypsin. The dissolution profiles of the insulin from the cSLN were characterized by a biphasic release. There was an initial burst release in the first 30 min, followed by a sustained release of the peptide. Moreover, compared to free insulin in solution, the cSLN developed significantly increased the passage of the encapsulated insulin through a monolayer of co-cultured Caco-2/HT29 cells. This went from 1.16 ± 0.27% to 2.89 ± 0.39% after 4 h, for the free insulin and the cSLN respectively.

Lipid carriers for delivery of celecoxib: In vitro, in vivo assessment of nanomedicine in rheumatoid arthritis

Celecoxib loaded tristearin lipid nanoparticles (CEL‐TS‐LN) formulation was prepared by micro emulsion technique. The prepared CEL‐TS‐LN formulations were characterized by photon correlation spectroscopy (PCS), Zeta potential, transmission electron microscopy (TEM), in vitro release kinetics, In vivo toxicity and pharmacokinetics; and Freund's adjuvant‐induced arthritic studies were conducted. The mean diameter of the CEL‐TS‐LN was about 188 nm; the particles had spherical morphology and an amorphous nature. In vitro drug release study of CEL‐TS‐LN revealed sustained drug release of 62% for 36 hrs; and the drug release was found to follow zero order and Fickian diffusion mechanism. The biochemical and haematology reports of in vivo toxicity studies revealed that CEL‐TS‐LN does not exhibit any toxic symptoms on vital organs and could be safe. With 88% percent inhibition of edema, serum biochemical parameters of CEL‐TS‐LN treated animal groups showed significant difference (p &lt; 0.05) compared to arthritic control (without treatment). In conclusion, the results clearly suggested that CEL‐TS‐LN facilitated sustained release enhanced bioavailability and improved therapeutic efficiency of the encapsulated celecoxib drug.Practical applications: In this paper we stress the importance of solid lipid nanoparticles for oral delivery. We also discuss the feasibility of large scale production of celecoxib loaded tristearin lipid nanoparticles (CEL‐TS‐LN) by micro emulsion technique for industrial application. Celecoxib (CEL) has been recommended as oral use for the treatment of rheumatoid arthritis (RA). Low oral bioavailability and long term oral administration of CEL produces severe gastrointestinal side effects. CEL‐TS‐LN holds promise for safe, improved bioavailability and enhanced therapeutic efficiency in the treatment of RA.Successfully incorporated celecoxib into tristearin solid lipid Nanoparticles (CEL‐TS‐LN).The optimized CEL‐TS‐LN preparation was exhibited spherical morphology, amorphous nature, maximum entrapment efficiency and sustained release of celecoxib. CEL‐TS‐LN does not exhibit any toxic symptoms, enhanced bioavailability and therapeutic efficiency in In Vivo.

Solid Lipid Nanoparticles for Oral Delivery of Decitabine: Formulation Optimization, Characterization, Stability and Ex-Vivo Gut Permeation Studies

Solid Lipid Nanoparticles for Oral Delivery of Decitabine: Formulation Optimization, Characterization, Stability and <i>Ex-Vivo</i> Gut Permeation Studies

Surface-modified solid lipid nanoparticles for oral delivery of docetaxel: enhanced intestinal absorption and lymphatic uptake

Docetaxel is a potent anticancer drug, but development of an oral formulation has been hindered mainly due to its poor oral bioavailability. In this study, solid lipid nanoparticles (SLNs) surface-modified by Tween 80 or D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS 1000) were prepared and evaluated in terms of their feasibility as oral delivery systems for docetaxel. Tween 80-emulsified and TPGS 1000-emulsified tristearin-based lipidic nanoparticles were prepared by a solvent-diffusion method, and their particle size distribution, zeta potential, drug loading, and particle morphology were characterized. An in vitro release study showed a sustained-release profile of docetaxel from the SLNs compared with an intravenous docetaxel formulation (Taxotere®). Tween 80-emulsified SLNs showed enhanced intestinal absorption, lymphatic uptake, and relative oral bioavailability of docetaxel compared with Taxotere in rats. These results may be attributable to the absorption-enhancing effects of the tristearin nanoparticle. Moreover, compared with Tween 80-emulsified SLNs, the intestinal absorption and relative oral bioavailability of docetaxel in rats were further improved in TPGS 1000-emulsified SLNs, probably due to better inhibition of drug efflux by TPGS 1000, along with intestinal lymphatic uptake. Taken together, it is worth noting that these surface-modified SLNs may serve as efficient oral delivery systems for docetaxel.

Lipid nanoparticles for oral delivery of raloxifene: Optimization, stability, in vivo evaluation and uptake mechanism

Raloxifene HCl (RLX) shows low oral bioavailability (<2%) in humans due to poor aqueous solubility and extensive (>90%) metabolism in gut. Lipid nanoparticles (SLN) with glyceryl tribehenate were designed to enhance drug’s oral bioavailability. Box–Bhenken design was used to optimize manufacturing conditions. Optimized SLN had particle size of 167±3nm and high encapsulation efficiency (>92%). Oral bioavailability of RLX from SLN was improved by 3.24 folds compared to free RLX in female Wistar rats. Both clathrin and caveolae mediated endocytosis pathways were involved in the uptake of SLN. Lymphatic transport inhibitor, cycloheximide significantly reduced oral bioavailability of SLN.

Preparation and optimization of triptolide-loaded solid lipid nanoparticles for oral delivery with reduced gastric irritation.

Triptolide (TP) often causes adverse reactions in the gastrointestinal tract when it is administered orally. This study aimed to prepare and optimize triptolide-loaded solid lipid nanoparticles (TP-SLN) with reduced gastric irritation. The microemulsion technique was used to formulate TP-SLN employing a five-level central composite design (CCD) that was developed for exploring the optimum levels of three independent variables on particle size, encapsulation efficiency (EE) and drug loading (DL). Quadratic polynomial models were generated to predict and evaluate the three independent variables with respect to the three responses. The optimized TP-SLN was predicted to comprise fraction of lipid of 49.73%, surfactant to co-surfactant ratio of 3.25, and lipid to drug ratio of 55.27, which showed particle size of 179.8 ± 5.7 nm, EE of 56.5 ± 0.18% and DL of 1.02 ± 0.003% that were in good agreement with predicted values. In addition, the optimized nanoparticles manifested a sustained-release pattern in vitro and were stable during 3 h of incubation in simulated gastric fluids without significant size change and the majority (91%) of the drug was protected. Furthermore, the nanoparticles did not show obvious gastric irritation caused by oral administration of TP in rats.