Delivery Of Indomethacin Research Articles

Tailoring pH-sensitive carboxymethyl tamarind kernel gum-based hydrogel for an efficient delivery of hydrophobic drug indomethacin

Polyacrylamide hydrogels have gained attention in the drug delivery field for their pH-dependent nature. Nevertheless, their limited degradability and lower entrapment efficiency for hydrophobic drugs hinder their utility in controlled drug release. This research aims to design a degradable pH-sensitive hydrogel for delivering the hydrophobic drug indomethacin to the colon. This work developed and optimized the hydrogels based on β-cyclodextrin, carboxymethyl tamarind kernel gum, and polyacrylamide with varying amounts of polyethylene glycol diacrylate. The optimized hydrogel exhibits 76.52 % gel fraction, 89.21 % porosity, 1000.27 % swelling, and 90.0 % equilibrium water content. The hydrogel was characterized using Attenuated Total Reflection-Fourier Transform Infrared spectroscopy, confirming the successful crosslinking of the synthesized hydrogel. Powder X-ray Diffraction revealed their amorphous nature while Scanning Electron Microscopy showed a porous surface morphology of the hydrogel. Moreover, rheology confirmed the hydrogel's elastic nature. Notably, the hydrogel demonstrated a drug release of 60.26 % at pH 7.4. Kinetic modelling of indomethacin release data indicated a Fickian diffusion release mechanism. Cytotoxicity tests on HCT-116 cells showed 79 % viability, and the hydrogel fully degraded within 10 days. These results confirmed the potential of synthesized β-CD/PAM/CMTKG hydrogel for controlled indomethacin delivery to the colon.

Indomethacin Delivery from PCL Nanofibrous Scaffolds Enhances Biomineralization and Cell Adhesion: Biocompatible Scaffold Model for Teeth Regeneration

Indomethacin Delivery from PCL Nanofibrous Scaffolds Enhances Biomineralization and Cell Adhesion: Biocompatible Scaffold Model for Teeth Regeneration

Biofabrication of 3D adipose tissue via assembly of composite stem cell spheroids containing adipo-inductive dual-signal delivery nanofibers

Reconstruction of large 3D tissues based on assembly of micro-sized multi-cellular spheroids has gained attention in tissue engineering. However, formation of 3D adipose tissue from spheroids has been challenging due to the limited adhesion capability and restricted cell mobility of adipocytes in culture media. In this study, we addressed this problem by developing adipo-inductive nanofibers enabling dual delivery of indomethacin and insulin. These nanofibers were introduced into composite spheroids comprising human adipose-derived stem cells (hADSCs). This approach led to a significant enhancement in the formation of uniform lipid droplets, as evidenced by the significantly increased Oil red O-stained area in spheroids incorporating indomethacin and insulin dual delivery nanofibers (56.9 ± 4.6%) compared to the control (15.6 ± 3.5%) with significantly greater gene expression associated with adipogenesis (C/EBPA, PPARG, FABP4, and adiponectin) of hADSCs. Furthermore, we investigated the influence of culture media on the migration and merging of spheroids and observed significant decrease in migration and merging of spheroids in adipogenic differentiation media. Conversely, the presence of adipo-inductive nanofibers promoted spheroid fusion, allowing the formation of macroscopic 3D adipose tissue in the absence of adipogenic supplements while facilitating homogeneous adipogenesis of hADSCs. The approach described here holds promise for the generation of 3D adipose tissue constructs by scaffold-free assembly of stem cell spheroids with potential applications in clinical and organ models.

Combination of Indomethacin with Nanostructured Lipid Carriers for Effective Anticancer Therapy.

The anticancer potential of indomethacin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in vitro, in vivo, and in clinical trials is well known and widely reported in the literature, along with their side effects, which are mainly observed in the gastrointestinal tract. Here, we present a strategy for the application of the old drug indomethacin as an anticancer agent by encapsulating it in nanostructured lipid carriers (NLC). We describe the production method of IND-NLC, their physicochemical parameters, and the results of their antiproliferative activity against selected cancer cell lines, which were found to be higher compared to the activity of free indomethacin. IND-NLC were fabricated using the hot high-pressure homogenization method. The nanocarriers were physicochemically characterized, and their biopharmaceutical behaviour and therapeutic efficacy were evaluated in vitro. Lipid nanoparticles IND-NLC exhibited a particle size of 168.1 nm, a negative surface charge (-30.1 mV), low polydispersity index (PDI of 0.139), and high encapsulation efficiency (over 99%). IND-NLC were stable for over 60 days and retained integrity during storage at 4 °C and 25 °C. The potential therapeutic benefits of IND-NLC were screened using in vitro cancer models, where nanocarriers with encapsulated drug effectively inhibited the growth of breast cancer cell line MDA-MB-468 at dosage 15.7 μM. We successfully developed IND-NLC for delivery of indomethacin to cancer cells and confirmed their antitumoral efficacy in in vitro studies. The results suggest that indomethacin encapsulated in lipid nanoparticles possesses high anticancer potential. Moreover, the presented strategy is highly promising and may offer a new alternative for future therapeutic drug innovations.

Cationic Dextran Stearate (Dex-St-GTMAC): Synthesis and Evaluation as Polymeric Micelles for Indomethacin Corneal Penetration.

Background Indomethacin as a non-steroidal anti-inflammatory drug (NSAID) is commonly used to treat some ocular inflammatory disorders. Unfortunately, indomethacin is a drug that is poorly soluble in water; therefore, it has low efficacy. An attractive approach is the targeted delivery of indomethacin to the cornea using cationic dextran stearate as a polymeric micelle drug carrier. Methods A dextran stearate-glycidyl trimethylammonium chloride (Dex-St-GTMAC) copolymer was prepared through the reaction of GTMAC, stearoyl chloride, and dextran. Then, Dex-St-GTMAC was characterized by Fourier transform infrared (FT-IR) spectroscopy and 1H NMR spectroscopy. Dex-St-GTMAC forms micelles in the presence of indomethacin. The prepared polymeric micelles were characterized for size, ζ-potential, drug loading, particle morphology, critical micelle concentration, and encapsulation efficiency. To study the irritation potential of the indomethacin-loaded Dex-St-GTMAC, Het-Cam and Draize tests have been performed. Prepared cationic micelles were subjected to the in vitro drug release and ex vivotrans-corneal permeation test. Results The dialysis method was used for the preparation of indomethacin-loaded micelles (10, 20, and 30%). Measurement of the particle size showed a mean diameter of 122.1 and 150.9 nm for the drug-loaded micelles. Scanning electron microscopy (SEM) images showed that the morphology of the particles is spherical. 10% formulation was chosen as the best formulation due to more surface charge and reasonable drug loading. ζ-potential measurement for the 10% drug-containing micelles showed a value of +39.1 mV. Drug loading efficiency and the encapsulation efficiency for 10% drug-containing micelles were 6.36 and 63.61%, respectively. The results of the Het-Cam and Draize tests indicated that the indomethacin-loaded Dex-St-GTMAC formulation had no toxicity to eye tissues. Based on our results, the prepared micelles (indomethacin-loaded Dex-St-GTMAC) exhibited a sustained drug release pattern compared to the control group. Indomethacin penetration from the micelles to the excised bovine cornea was 1.75-fold greater than the control (indomethacin 0.1% in phosphate-buffered saline (PBS)). Conclusions Data from the ζ-potential, SEM, drug loading capacity, and in vitro drug release studies indicated that cationic dextran stearate polymeric micelles are an appropriate carrier for the efficient penetration of indomethacin into cornea tissues.

K-Carrageenan/sericin-based multiparticulate systems: A novel gastro-resistant polymer matrix for indomethacin delivery

This study aimed to develop a natural and multiparticulate carrier of k-carrageenan (k-Car) and sericin (Ser) for encapsulation of indomethacin (IND) in order to minimize gastrointestinal effects caused by immediate-release. Increasing the amount of IND in the formulations subtly reduced the entrapment efficiency (EE) and drug loading (DL) due to matrix saturation. Sericin was essential to improve EE and DL when compared to pure k-Car (EE > 90 % and DL > 47 %) with suitable particle sizes (1.3461 ± 0.1891–1.7213 ± 0.1586 mm). The incorporation and integrity of IND in the particles were confirmed by analytical techniques of HPLC, XRD, FTIR, and SEM. Additionally, the k-Car/Ser matrix was pH-responsive with low IND release at pH 1.2 and extended-release at pH 6.8. The Weibull model had an adequate fit to the experimental data with R2aju 0.950.99 and AIC 82.4–24.9, with curves in parabolic profile (b < 1) and indicative of a controlled drug-release mechanism by diffusion. Besides, k-Car/Ser/IND and placebo were not cytotoxic (cell viability > 85 % at 150–600 μM) for the Caco-2 cell line. Therefore, the polymeric matrix is gastro-resistant, stable, and biocompatible to carry indomethacin and deliver it to the intestinal environment.

Hyaluronan-modified transfersomes based hydrogel for enhanced transdermal delivery of indomethacin

Hyaluronic acid (HA), as a hygroscopic and biocompatible molecule, has displayed unique permeation enhancement in transdermal delivery systems. Hence, indomethacin (IND) was encapsulated in HA-modified transfersomes (IND-HTs) to enhance transdermal IND delivery to reduce adverse effects in this study. The physiochemical properties of IND-HTs were characterized. Results showed that the prepared IND-HTs were spherical and revealed good entrapment efficiency (87.88 ± 2.03%), with a nanometric particle size (221.8 ± 93.34 nm). Then, IND-HTs were further incorporated into a carbopol 940 hydrogel (IND-HTs/Gel) to prolong retention capacity on the skin. The in vitro release and skin permeation experiments of IND-HTs/Gel were carried out with the Franz diffusion cells. It was found that IND-HTs/Gel exhibited sustained drug release, as well as superior drug permeation and flux across the skin. Confocal laser scanning microscopy showed improved penetration of HTs/Gel with a wider distribution and higher fluorescence intensity. The hematoxylin–eosin stained showed that HA improved the transdermal effect by changing the microstructure of skin layers and decreasing skin barrier function. In addition, IND-HTs/Gel showed significant analgesic activity in hot plate test and no potentially hazardous skin irritation. This study indicated that the developed IND-HTs/Gel could be a promising alternative to conventional oral delivery of IND by topical administration.

Hybrid Nanobeads for Oral Indomethacin Delivery.

The oral administration of the anti-inflammatory indomethacin (INDO) causes severe gastrointestinal side effects, which are intensified in chronic inflammatory conditions when a continuous treatment is mandatory. The development of hybrid delivery systems associates the benefits of different (nano) carriers in a single system, designed to improve the efficacy and/or minimize the toxicity of drugs. This work describes the preparation of hybrid nanobeads composed of nanostructured lipid carriers (NLC) loading INDO (2%; w/v) and chitosan, coated by xanthan. NLC formulations were monitored in a long-term stability study (25 °C). After one year, they showed suitable physicochemical properties (size < 250 nm, polydispersity < 0.2, zeta potential of −30 mV and spherical morphology) and an INDO encapsulation efficiency of 99%. The hybrid (lipid-biopolymers) nanobeads exhibited excellent compatibility between the biomaterials, as revealed by structural and thermodynamic properties, monodisperse size distribution, desirable in vitro water uptake and prolonged in vitro INDO release (26 h). The in vivo safety of hybrid nanobeads was confirmed by the chicken embryo (CE) toxicity test, considering the embryos viability, weights of CE and annexes and changes in the biochemical markers. The results point out a safe gastro-resistant pharmaceutical form for further efficacy assays.

Enzyme-Instructed Self-Assembly of Anticancer Peptide Facilitates Selective Cellular Delivery of Indomethacin

Enzyme-Instructed Self-Assembly of Anticancer Peptide Facilitates Selective Cellular Delivery of Indomethacin

Mixed Micelles Loaded Dissolving Microneedles for Enhanced and Sustained Transdermal Delivery of Indomethacin

Mixed Micelles Loaded Dissolving Microneedles for Enhanced and Sustained Transdermal Delivery of Indomethacin

The effects of iontophoresis and electroporation on transdermal delivery of indomethacin evaluated in vitro and in vivo

The objective of this study was to evaluate the transdermal delivery of indomethacin in vitro and in vivo enhanced by iontophoresis and/or electroporation through several barriers. Excised Wistar rat skin, pig skin, human epidermal membrane and cellulose membrane were tested for the in vitro indomethacin permeation, whereas drug concentration of in the plasma was analyzed to monitor the percutaneous absorption in Wistar rat in vivo. Iontophoresis enhanced the in vitro transdermal delivery of indomethacin as compared to the passive diffusion. Pulsing of high voltages, as known as electroporation, followed by iontophoresis did result in a synergistic effect in contrast to iontophoresis or electroporation alone. The in vitro result indicated that higher drug permeation could be induced during and after the application of iontophoresis. In some case, the permeation could benefit from the electroporation in term of cumulative amount within 12 hr. Furthermore, the combination of electroporation and iontophoresis resulted in a higher permeation amount than iontophoresis or electroporation alone did. Both iontophoresis and the combination protocol could reduce interspecies difference in vitro. The in vivo results were similar to that of in vitro ones. Iontophoresis and electroporation/iontophoresis resulted in higher AUC (area under curve) of blood concentration profiles of indomethacin. In addition, the combination protocol significantly induced higher transepidermal water loss (TEWL). It is concluded that the in vivo permeation results did correspond to the enhancement efficiency of the in vitro experiments.

Interpolymer Complexes of Eudragit® Copolymers as Novel Carriers for Colon-Specific Drug Delivery.

Interpolymer complexes (IPC) based on Eudragit® EPO and Eudragit® S100 were investigated as potential carriers for oral controlled drug delivery to the colon. IPC samples were prepared by mixing copolymer solutions in organic solvents (ethanol, isopropanol:acetone mixture (60:40, % v/v) and tetrahydrofuran). According to the data of elemental analysis, FTIR-spectroscopy, X-ray photoelectron spectroscopy and thermal analysis these IPCs have excess of anionic copolymer (Eudragit® S100) in their structure; they are stabilized by hydrogen and ionic intermacromolecular bonds and do not include free copolymer domains. IPC have pH-independent swelling properties in the media mimicking gastrointestinal tract (GIT) conditions and provide colon-specific delivery of indomethacin in buffer solutions (pH 1.2; 5.8; 6.8; 7.4) and in biorelevant media (fasted state simulated gastric fluid, fasted state simulated intestinal fluid—version 2 and fasted stated simulated colonic fluid).

DEVELOPMENT OF NANOEMULSION TO IMPROVE THE OCULAR BIOAVAILABILITY AND PATIENT COMPLIANCE IN POSTOPERATIVE TREATMENT USING INDOMETHACIN

Objective: To develop a new cationic nanoemulsion (NE) for ophthalmic delivery of indomethacin (IND) to improve the permeability and retention time of formulations, thereby improving the drug's ocular bioavailability.&#x0D; Methods: Based on the solubility profile of indomethacin in various solvents, captex 8000 was selected as oil phase, span 20 as a surfactant and tween 20 as co-surfactant to construct pseudo ternary phase diagrams and nanoemulsion region was recognized. Sonication was used as the method of NE preparation. Optimization was done using 32 factorial designs by considering the oil and the ratio of surfactant to co-surfactant (Smix) quantities as independent variables and evaluated for different physicochemical properties. Ex vivo transcorneal permeability was studied using bovine cornea, the In vivo drug pharmacokinetics of optimized NE and marketed formulation were assessed in rabbit aqueous humor and also in plasma.&#x0D; Results: The mean globule size, zeta potential, viscosity, refractive index, pH, surface tension and the osmolarity values for the prepared indomethacin nanoemulsions (IND-NEs) were found between 129.8±1.1 to 191.4±1.6 nm,+13.20±4.6 to+23.45±4.82, 15.3±0.1 to 32.7±0.0 mPas, 1.346±0.007 to 1.386±0.005, 5.5±0.4 to 6.9±0.9, 32.0±2.6 to 52.3±3.4 mN/m and 303-395 mOsm/l respectively and all these values found to be falling under the recommended values for ophthalmic use. From the In vitro release studies, it was found that the IND-NEs exhibited sustained drug release with 67.91±2.01 to 95.90±1.93 % drug release at 24h when compared to the drug solution which showed 99.81±5.21 % drug release within 2h. The Ex vivo drug permeation through the corneal membrane at 4h from the optimized NE and drug solution was found to be 524±1.5 µg/cm2 and 175±2.6 µg/cm2 respectively. Further, the optimized NE was found to be nonirritant with the lowest ocular irritation potential (Iirr) of 1 towards the rabbit's eyes. The area under the drug concentration vs. time curve for 24h (AUC (0–24h)) for optimized NE and the marketed formulation was found to be 1514.99 ng/ml/h and 974.14 ng/ml/h in aqueous humour; 2266.83 ng/ml/h and 778.15 ng/ml/h in plasma respectively.&#x0D; Conclusion: Due to its improved corneal absorption and prolonged drug release along with less systemic absorption, the optimized NE offers an effective postoperative treatment with increased ocular bioavailability and improved patient compliance with a decrease in the number of installations per day and a decrease or disappearance of systemic side effects of IND.

Ultrasound-Assisted Facile Synthesis of Nanostructured Hybrid Vesicle for the Nasal Delivery of Indomethacin: Response Surface Optimization, Microstructure, and Stability

This work is devoted to design a novel nanostructured hybrid vesicle (NHV) made of lecithin and an acrylate/C10-C30 alkyl acrylate for the nasal delivery of a model active indomethacin (IND), and further to probe its microstructure, intermolecular interactions, drug release behavior, ex vivo permeation, and stability. NHVs were prepared by cavitation technology employing RSM-based central composite design (CCD). Amount of lecithin (X1), power of ultrasound (X2), and sonication time (X3) were selected as three independent variables while the studied response included Z-Avg (nm), polydispersity index (PDI), and zeta potential (mV). The designed system (NHV) was investigated through dynamic (DLS) and electrophoretic light scattering (ELS), attenuated total reflectance (ATR-FTIR), oscillatory measurement (stress and frequency sweep), and transmission electron microscopy (TEM). CCD was found useful in optimizing NHV. An optimized formulation (S6) had Z-Avg 80nm, PDI 0.2, and zeta potential of - 43.26mV. Morphology investigation revealed spherical vesicles with smaller TEM diameters (the largest particle being 52.26nm). ATR analysis demonstrated significant intermolecular interactions among the drug (IND) and the components of vesicles. The designed vesicles had an elastic predominance and displayed supercase II (n > 1) type of drug release. Besides, the vesicles possessed potential to transport IND across the nasal mucosa with the steady-state flux (μg/cm2/h) and permeability coefficient (cm/h) of 26.61 and 13.30 × 10-3, respectively. NHV exhibited an exceptional stability involving a combination of electrostatic and steric interactions while the histopathology investigation confirmed their safety for nasal administration.

Effect of Shape on Mesoporous Silica Nanoparticles for Oral Delivery of Indomethacin.

The use of mesoporous silica nanoparticles (MSNs) in the field of oral drug delivery has recently attracted greater attention. However, there is still limited knowledge about how the shape of MSNs affects drug delivery capacity. In our study, we fabricated mesoporous silica nanorods (MSNRs) to study the shape effects of MSNs on oral delivery. MSNRs were characterized by transmission electron microscopy (TEM), nitrogen adsorption/desorption, Fourier transform infrared spectroscopy (FTIR), and small-angle X-ray diffraction (small-angle XRD). Indomethacin (IMC), a non-steroidal anti-inflammatory agent, was loaded into MSNRs as model drug, and the drug-loaded MSNRs resulted in an excellent dissolution-enhancing effect. The cytotoxicity and in vivo pharmacokinetic studies indicated that MSNRs can be applied as a safe and efficient candidate for the delivery of insoluble drugs. The use of MSNs with a rod-like shape, as a drug delivery carrier, will extend the pharmaceutical applications of silica materials.

Controlled Release Binary and Ternary HPMC-HPC-Gelucire® 50/13 Hybrids Based Solid Dispersions of Indomethacin: In vitro Evaluation and In vivo Anti-inflammatory Studies

Aim: The aim of this study is to formulate and evaluate solid dispersions of indomethacin based on Gelucire 50/13, Hydroxylpropyl methylcellulose and/or Hydroxylpropyl cellulose hybrid binary or ternary system, with a view of enhancing oral bioavailability, sustaining drug release with optimum anti-inflammatory activity and minimal side effects. Methodology: Solid dispersions were prepared by solvent-evaporation method at varying polymer ratios (with HPMC and Gelucire 50/13 at 1:1, 2:1, 3:1, 4:1, 1:2, 1:3, 1:4 and HPMC, HPC and Gelucire 50/13 at 1:1:1) with a constant concentration of indomethacin (100 mg). The formulations were characterized in terms of morphology, stability and drug content. The release profiles of indomethacin from the solid dispersions were examined in vitro using two different media i.e. SGF and SIF, without enzymes. The anti-inflammatory properties were evaluated. Results: The formulated solid dispersions were stable and almost spherical to irregularly-shaped. The drug content of the formulations was accepted according to the Pharmacopoeial limit. In vitro dissolution studies showed an increased dissolution rate at pH 7.4 compared to pH 1.2 for the various batches with solid dispersions showing a faster and sustained dissolution rate than the pure crystalline drug. The percentage inhibitions of edema produced by the formulations in the in vivo studies were significantly higher and sustained than the pure drug. Conclusion: Solid dispersions prepared with these biodegradable polymer hybrids, HPMC/HPC/Gelucire® 50/13, showed promising potential in clinical practice for enhancing the delivery of indomethacin.

Optimization of eugenol microemulsion for transdermal delivery of indomethacin

The aim was to optimize eugenol microemulsion for transdermal delivery of indomethacin (model drug). Pseudo-ternary phase diagrams were constructed using Tween 40 (surfactant) in presence and absence of ethanol or propylene glycol (PG) as co-surfactants. Microemulsion formulations containing eugenol at 10, 20 and 30% w/w with 60% w/w of surfactant or surfactant/co-surfactant were evaluated for indomethacin loading, release and transdermal delivery. Transdermal delivery was assessed using rabbit ear model. The phase diagrams reflected the ability of Tween 40 to form eugenol microemulsion with addition of ethanol or PG increasing the microemulsion zone. Indomethacin loading in microemulsion was increased by increasing eugenol concentration and in presence of co-surfactants. The release rate increased in presence of PG or ethanol. Indomethacin transdermal flux was greater from microemulsions containing high eugenol concentration with PG containing systems being superior. The study introduced eugenol microemulsion formulations for transdermal delivery and highlighted possible synergism with PG.

Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems

Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity.Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods.The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin.Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable indomethacin delivery system, with a great potential in industrial manufacturing.

Poly (ε-caprolactone) nanoparticles loaded with indomethacin and Nigella Sativa L. essential oil for the topical treatment of inflammation

Indomethacin has a high anti-inflammatory potential and an acceptable efficiency for external application. However, indomethacin can cause several side effects. It is crucial to reduce the employed indomethacin dosage and accordingly associated side effects. Therefore, topical delivery of indomethacin is as an interesting strategy. Thus, we designed poly (ε-caprolactone) based nanoparticles loaded with the Nigella Sativa L. Seeds Essential Oil (NSSEO) and indomethacin to enhance analgesic and anti-inflammatory effects of indomethacin. Nanoparticles were prepared by nanoprecipitation method. Prepared nanoparticles pre-stability study was also carried out. Nanoparticles size was ranged between 230 nm and 260 nm and zeta potential of nanoparticles was between – 20 mV and – 30 mV at pH around 6. Encapsulation efficiency of indomethacin and NSSEO within nanoparticles was respectively 70% and 84% while drug loading of indomethacin and NSSEO were 14% and 5.63% respectively. The size and zeta potential of nanoparticles was not changed significantly within 30 days of pre-stability investigation. Nanoparticles had a size in nano scale with round shape and a proper stability. Indomethacin and NSSEO were successfully encapsulated that would boost the anti-inflammatory and analgesic effects of indomethacin.

DEVELOPMENT AND CHARACTERIZATION OF INDOMETHACIN-LOADED MUCOADHESIVE NANOSTRUCTURED LIPID CARRIERS FOR TOPICAL OCULAR DELIVERY

Objective: To develop and characterize indomethacin loaded-nanostructured lipid carriers (IND-NLCs) for topical ophthalmic delivery with different particle sizes and polymer coating to improve the mucoadhesive property on the ocular surface.Methods: Nanostructured lipid carriers (NLCs) with different solid lipids and surfactants were prepared by the high-pressure homogenization technique. The optimized IND-NLCs was coated with polyethylene glycol 400 (PEG). The physicochemical properties and entrapment efficacy (EE) were examined. In vitro release studies were investigated using the shake-flask method. Ex vivo mucoadhesive studies were assessed by the wash-off test. In addition, the cytotoxicity was assessed by the short time exposure test.Results: IND-NLCs of ~300 and ~40 nm in diameter were successfully produced with a zeta potential of -30 mV and EE of 60–70 %. IND-NLCs prepared with Tween 80 as surfactant could be sterilized by autoclaving. The PEG coating of IND-NLCs did not affect either the particle size or EE. In vitro release showed a prolonged release for 360 min with a burst release of 50-60% occurring within 5 min. The smaller-sized IND-NLCs showed slightly faster release rates and better mucoadhesion to cornea compared to the larger IND-NLCs. PEG-coated IND-NLCs showed the highest mucoadhesion. In addition, IND-NLCs showed less cytotoxicity compared to IND alone. Conclusion: The small and PEG-coated NLCs represents a potentially useful carrier for safe delivery of indomethacin to the ocular surface with increased residence time.