Solvent Diffusion Technique Research Articles

PREPARATION AND IN VITRO CHARACTERIZATION OF SOLID LIPID MICROPARTICLES FOR PROTEIN DELIVERY

Objective: The aim of this research was to assess the effect of the process and formulation parameters during the preparation of solid lipid microparticles. Solid lipid microparticles (SLMs) have evident advantages such as biocompatibility, simplicity of production and characterization, prolonged release, and especially high protein loading capacity, despite being less investigated than lipid nanoparticles.Material and Method: SLMs were prepared via emulsion solvent diffusion technique using glyceryl tridecanoate (GTD) as a biocompatible and biodegradable lipid. The optimum formulation conditions for producing homogenous spherical microparticles were found and represented by a triangle phase diagram area. After optimizing the particle size and encapsulation efficiency by changing the formulation parameters, the microparticles were characterized by in vitro release, morphological analysis, thermal analysis and electrophoretic analysis on the selected formulations.Result and Discussion: The maximum drug loading efficiency was achieved by combining 100 mg of lipid, 60% triacetin and 3% emulsifier. The average microparticle size was observed as 8.9 μm. The in vitro drug release were analyzed in pH 7.4 phosphate buffer and were mainly completed at 8th hour.

Formulation and evaluation of orlistat loaded microsponges for the treatment of obesity

The motivation behind this investigation was to design novel drug delivery system containing orlistat micro sponges. Microsponges containing orlistat and Ethyl cellulose/ Eudragit RS 100 prepared by quasi emulsion solvent diffusion (Technique) method. The formulations were prepared step by step increases Drug: polymer ratio. The particle size (Malvern analyzer), Surface Morphology and structure examination (SEM) Production yield, Drug entrapment Efficiency and in vitro drug release studied of microsponges were examined. Shape or surface morphology and topography of the orlistat microsponges were examined by scanning electron microscopy. The drug orlistat disperse in GIT for better therapeutic effect as microsponges disperse freely in GIT. To improve absorption of orlistat so as to enhance bioavailability, micro sponges is used as delivery systems which show better absorption and bioavailability then other dosage form of orlistat. The particle size were prepared microsponges was observed in the range of 50.45 ± 0.85µm to 57.77 ± 1.35µm. The drug entrapment of the orlistat microsponges was observed in the range of 73.23 ± 0.23 to 83.41 ± 1.17 % The in vitro drug release study of the microsponges over 8 hour range from 59.28 ± 0.41% to 73.16 ± 0.89 %. The objective of this research work was to formulation and evaluation of orlistat loaded microsponges for management of obesity disease. Microsponges drug delivery system landscape have been highly and rapidly evolving. They are allowing for novel product form. Microsponges are safe biologically and extraordinary preferred position programmable release. This delivery system are being integrated to optimize the efficacy or free streaming effectiveness treatment.

Formulation and evaluation of polymeric microspheres of a poorly soluble drug celecoxib

The aim of this present work was to formulate microspheres of BCS Class II drug Celecoxib. The drug was identified by melting point study and FT-IR spectroscopy. Therapeutic success of a drug is greatly depended on its bioavailability. Majority of the recently discovered drugs shows poor solubility (BCS Class II) which decreases the bioavailability upon oral administration. Microspheres are a novel technique to circumvent this obstacle, which can increase bioavailability of drugs significantly. Polymeric microspheres with Polyvinylpyrrolidone and Eudragit L-100, prepared by Emulsion Solvent Diffusion and Evaporation technique, showed a range of drug release profile at intestinal pH 6.8. Different batches of microspheres were prepared by varying the drug-polymer ratio. Microparticulate systems like microspheres improve absorption which increases the bioavailability, ultimately leading to more efficient drug therapy. The microsphere system also provides protection to the gastric mucosa from GIT-irritant drugs thus decreasing toxic effects and sustained releases allows lower dosage frequency. Prepared microspheres were evaluated on various parameters like entrapment efficiency, %yield, particle size, scanning electron microscope analysis, and in-vitro drug release profile. Solid spherical microspheres were produced which showed good entrapment efficiency (43%-91%) and released 70-90% of the drug content in 10hrs.

Ocular Delivery of Atenolol Loaded Microsponge in-situ Gel: Development, Characterization and in-vitro Evaluation

Abstract: Aim/Background: The purpose of the study was to fabricate and evaluate atenolol loaded micro-sponge in-situ gel. Materials and Methods: Oil in Oil Emulsion Solvent Diffusion Technique was used for formulation of microsponges by using different levels of polymers such as Eudragit RS-100 and Ethyl Cellulose. The prepared micro-sponges were evaluated for optical microscopy, percentage yield, drug content, entrapment efficiency and surface morphology studies. The micro sponges were loaded into in-situ gel. The gel was characterized for pH, rheological behavior, in vitro gelling capacity and in vitro drug release study. Results: The smicrosponges were found in the size range of 7.43 to 9.26μm. The formulation F1 has smallest particle size while F9 has largest size. The product yield varies from 66.98% to 89.87 %.The drug content was found to be maximum for formulation F8 which is 94.19%. Similarly, the entrapment efficiency was found maximum for formulation F8 which is 93.89%. The gel was characterized for pH. The pH of drug loaded microsponge gel were found in range of 7.43±0.27 to 9.26±0.61.Similarly, viscosity ranges from 32 to 39 cps. The data of in-vitro release shows that 60.12% drug was released up to 24hr. Conclusion: The mirosponges laden in situ gel was effectively prepared by oil in oil emulsion solvent diffusion method (O/O ESDM). Further, the formulation will provide benefits in terms of sustained/controlled release, reduces dosing frequency and provides better compliance to the patient. Key words: Microsponge, Atenolol, Ethyl Cellulose, Eudragit RS-100, in situ gel.

Formulation and Evaluation of Lamotrigine Loaded Nanosponges

The main purpose of this investigation study is to fabricate nanosponges with good entrapment efficiency and percentage of yield to enhance the solubility and dissolution rate of poorly water soluble antiepileptic molecules of Lamotrigine, which belongs to BCS - II class. Lamotrigine nanosponges were prepared using emulsion solvent diffusion technique and the immediate release tablets of lamotrigine nanosponges were prepared by direct compression method. Nanosponges were formulated using different polymers ratio like EC and PVA. The optimized batch containing ratio 2:1:2 of drug, ethyl cellulose and PVA shows maximum entrapment efficiency and percentage of yield. The optimized nanosponges of lamotrigine (F1) were subjected for Practical yield, drug content, Saturation solubility, zeta potential, Fourier transform Infrared spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and Scanning electron microscopy(SEM). The optimized formulations (F1) of nanosponge based immediate release tablets compression parameters were also studied. The In-vitro dissolution was carried out by USP apparatus type II (Paddle Method) with 900 ml of 0.1 N HCl at 50 rpm. At definite time intervals, 5 ml of the receptor fluid were withdrawn, filtered and analyzed spectro-photometrically at wave length 265 nm. The compressed lamotrigine nanosponge shows 99.7% at the end of dissolution and it follows first order kinetics and best fit with Higuchi’s model. In this research solubility and dissolution demonstrated for nanosponge formulation.

Formulation and Evaluation of Gastroretentive Floating Microspheres of Rilpivirine Hydrochloride

Background: Systems of floating drug delivery have a bulk density less than gastric fluids and thus it remains buoyant in the stomach without having any effect on gastric emptying rate for prolonged period of time. Rilpivirine is an antiviral drug is used to treat human immunodeficiency virus (HIV), to combat the spread of (HIV), delivery of long acting; antiretroviral (ARV) drugs would be very beneficial for prevention and treatment. However the poor bioavailability of the drug requires attention in improving it and the technique of floating microspheres was investigated for the same objective. Methods: Floating microspheres of Rilpivirine are formulated by Emulsion – solvent diffusion technique using Ethyl cellulose and carbopol as polymers. The floating microspheres were subjected to evaluation for micrometric properties, percentage yield, particle size, drug polymer compatibility, scanning electron microscopy (SEM) and in vitro drug release studies and kinetics of drug release. Results: The results show that as the polymer concentration increases, the particle size, percentage yield, in vitro drug release was affected of floating microspheres. The micromeritic test was performed to confirm the particle size, and SEM results confirmed their hollow structure with smooth surface. Optimized formulation has shown good percentage yield, encapsulation efficiency, drug release was 98.25% at the end of 12 hr, the release was found to follow fickian diffusion with excellent drug release for long period of time. Conclusion: The results conclude that floating microspheres formulation of rilpivirine HCl could be effective tool in improving the bioavailability of drug for improved absorption.

Formulation Development and Evaluation of Colon Targeting Nanosponges of Deflazacort Using Box Behnken Design

Deflazacort is a glucocorticoid that is often used as an anti-inflammatory and immunosuppressant for patients suffering from Inflammatory Bowel Disease such as ulcerative colitis (UC) and Crohn's disease (CD). IBD is difficult to manage, and the most difficult issue for doctors is the recurrence. There are several regulated and colon focused medication delivery devices available for therapy, however they have a low success rate. The goal of this work was to create nanosponges loaded with deflazacort using the quasi-emulsion solvent diffusion technique using Eudragit S-100 and to investigate the influence of process factors on response using the Box-Behnken design. The effect of three independent parameters, Eudragit S100, PMMA, and PVA, on two dependent responses, particle size and percent drug entrapment, was investigated. Using the Box-behnken design, seventeen nanosponge formulations were created using the quasi-emulsion solvent diffusion technique and Eudragit S-100 (0.2 percent to 0.5 percent w/v), PMMA (0.2 percent to 0.5 percent w/v), and PVA (0.5 percent -1.5 percent w/v). Particle size, percent drug entrapment, shape and surface morphology, drug content determination, and in vitro drug release behaviour were all evaluated in the nanosponge formulations. The generated nanosponge was virtually spherical in form and spongy in character, with particle size 170.45 nm and a drug entrapment percentage of 73.42 percent. Over a 24-hour period, in vitro drug release of optimised formulations was shown to have a maximum drug release of 90.33.3 percent in colonic fluid with 4 percent w/v caecal content. The observed values of several assessment parameters were found to be in close agreement with the projected values using the Design expert programme. The nanosponge formulation obtained using Eudragit S-100 in low concentration, optimum concentration ratio of eudragit: PVA along with low stirring speed showed desired features. The mathematical models were further designed to develop nanosponge with required characteristics.

Preclinical evaluation from in-silico to in-vivo study of polyherbal microsponge sunscreen gel.

Electromagnetic spectrum of the UV region predominantly becomes the reason for skin's detrimental effects that give the genesis of innumerable skin ailments; because of this reason, the sunscreen products are required before condition in day to day lifestyle; products such as moisturizers, lotions, creams, shampoos, and other hair and skin preparations are accessible and accompanied by sunscreen properties, but they do not provide extended effect, also causes side effects due to harsh chemicals. The present study focuses on the effects of polyherbal extracts containing Microsponge gel for the protection of skin from ultraviolet rays. In the present research, already prepared Microsponge gel through quasi-emulsion solvent diffusion (QESD) technique was used for the HPLC, in-silico, in-vitro antioxidant activity, and in-vivo study. AdmetSAR software tool was utilized for the in-silico study, whereas for the in-vivo study, UV radiations are given on Albino rats using solarimeter. Results shown the active constituents are non-carcinogenic and non-toxic; IC50 values show good antioxidant activity and minimal effect of UV radiations after application of the gel formulation on animal skin. The results manifest prominent effects on animal skin further test for presence of ascorbic acid level and total protein in blood further verify the efficacy of the formulation. The study consequently established a strong ground for further extensive clinical studies.

ROSUVASTATIN CALCIUM NANOSPONGES IN THE FORMULATION OF EXTENDED RELEASE TABLETS

Cyclodextrin has been recognized as a linker molecule that can link with the various drug substances to produce a nano-porous structure called nanosponges (NS) and increase the dissolution rate of poorly soluble drug substances. This work aimed to load rosuvastatin calcium (RSC) with solubility enhancer’s β-cyclodextrin (β-CD) or polyvinyl alcohol (PVA). β-CD based RSC-NS were fabricated by the emulsion solvent diffusion technique; with solubilizer dichloromethane and different ratios of ethyl cellulose as a co-polymer. Characterization of the prepared nanosponges was done by various testing procedures that confirm its nanosize and particle size and drug release. RSC loading in NS was assessed by DSC, FTIR and SEM. Among all the formulations F5 has 78.23 % entrapment efficiency. 2-3 folds of increased solubility were obtained with RSC-NS. F1-F6 formulations released 76.35 % - 98.69 % of the drug at the end of 30 min. In the preparation of extended-release tablets, NS prepared from F5 formulation was used and the best tablet formulation was selected based on various evaluation tests. All the formulations except S3, S8 followed first-order release kinetics. S1 & S2 drug release mechanism is Higuchi while other formulations are Korsemeyer-Peppas, so the release mechanism for most of the formulations is erosion than diffusion.

Formulation and Evaluation of Kaempferol Loaded Nanoparticles against Experimentally Induced Hepatocellular Carcinoma: In Vitro and In Vivo Studies.

The present study was designed to prepare Kaempferol loaded nanoparticles (KFP-Np) and evaluate hepatoprotective and antioxidant effects in hepatocellular carcinoma models. KFP was encapsulated with hydroxypropyl methylcellulose acetate succinate (HPMC-AS) and Kollicoat MAE 30 DP polymers to prepare nanoparticles (Nps) by quasi-emulsion solvent diffusion technique (QESD). The prepared Nps were evaluated for different pharmaceutical characterization to select the optimum composition for the in vivo assessment. An animal model of cadmium chloride (CdCl2)-induced hepatocellular carcinoma in Male Sprague Dawley rats was used in vivo to test the antioxidant and hepatoprotective capacity of free and encapsulated KFP. The prepared Npsshowed nanometric size, low PDI, high drug load as well as encapsulation with a better drug release profile. There was a significant decrease in the increased serum levels of alanine transaminase (ALT), total bilirubin (TBiL), and aspartate transaminase (AST), and the lipid peroxidation’s (MDA) level was attenuated, and levels of markers of the cell antioxidant defence system were restored including Glutathione S-transferase (GST), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) via oral pre-treatment with KFP-Np (50 mg/kg b.w. (body weight), 6 weeks). KFP-Np significantly declines an mRNA expression of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) as well as decreased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein expression. It also upregulated the mRNA expression and protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). While comparing the protective effects of KFP encapsulated in Kollicoat MAE 30 DP and HPMC-AS, Nps was found to be betterthan free KFP. Insummary, result indicate that encapsulation of KFP in NPs provides a potential platform for oxidative stress induce liver injury.

Acetoxy DMU-loaded carboxymethylchitosan nanocapsules: preparation and in vitro release evaluation followed by an analytical methodology validation

ABSTRACT Acetoxy DMU (Ac.DMU – 1,2,3-trimethoxy-5-(4-acetoxystyryl) benzene) is a potential new drug, compared to resveratrol, due to its improved pharmacokinetic properties. Nanoencapsulation using Ac.DMU and carboxymethylchitosan (CMCh) polymer is a promising alternative for improving the bioavailability of drugs in human bodies. Nanocapsules (NCs) based on CMCh with Ac.DMU (Ac.DMU-NCs) by emulsion solvent diffusion technique in different drug-to-polymer ratios have been prepared with encapsulation efficiency of 69.4% and 51.5% and characterized by dynamic light scattering, ζ-potential, and infrared spectroscopy techniques. In vitro release experiments of free Ac.DMU and Ac.DMU-NCs showed an improvement in the solubility of Ac.DMU by NCs, enabling a fast drug release rate. In addition, the method was validated through analyses of specificity, linearity, limit of detection and quantification, accuracy, and precision according to the standards suggested by the International Conference on Harmonization. UV–Vis spectroscopy used to quantify Ac.DMU ensured reliable results for the amount of encapsulated Ac.DMU. The results suggest a promising potential of NCs as carriers of the hydrophobic drug Ac.DMU for controlled release.

Solubility Enhancement of Antihyperlipidemic Drug by Solvent Diffusion Technique

Poor aqueous solubility of drugs is major limiting factor with many new drugs in their successful launch in market in spite of their potential pharmacokinetic activity. Therefore, poor solubility is critical factor if the molecule is to survive the pharmaceutical development process. In the current work, it was planned to enhance the solubility of antihyperlipidemic drug by solvent diffusion technique. For this the drug clofibrate and excipients were procured and spherical agglomerates were prepared and evaluated. The findings of the study states the novelty the hypothesis.
 Keywords: Solubility, Diffusion, Agglomerates

Dapsone-Loaded Microsponge Gel for Acne Management: Preparation, Characterization and Anti-Microbial Activity

Background: Acne vulgaris is a chronic inflammatory disorder involving Propionibacterium acnes and activation of lymphocytes and neutrophils. Dapsone (sulfone drug) possesses potent anti-microbial activities and hence, it is used to cure multiple inflamed acne lesions. Howbeit, its therapeutic utility is hampered, owing to its poor solubility and side effects like mild irritation and dryness. These problems, along with orange-brown discoloration on skin, restrict the topical application of this drug. Objective: The objective of the present investigation was to address the above-mentioned limitations like irritation, dryness, and skin discoloration of dapsone via formulating microsponge based gel of this moiety. Methods: Dapsone microsponges were fabricated and embedded into a carbopol gel for topical application. The drug loaded ethylcellulose microsponges were crafted employing a quasi emulsion solvent diffusion technique. Besides routine characterization, these microformulations were assessed for entrapment, particle size analysis, and drug release. Furthermore, anti-acne potential was also evaluated against Propionibacterium acnes and Staphylococcus aureus to check their therapeutic efficiency. The prepared dapsone microsponge gel was assessed for its viscosity, spreadability, texture, and drug release. Results: Results revealed that dapsone loaded microsponges were successfully fabricated and found to possess good encapsulation efficiency (84.68 ± 5.73%), which is in micro-size range (88.06 ± 2.97 μm to 315.87 ± 1.99 μm) and showed cumulative drug release of 52.52 ± 0.2%. Field emission scanning electron microscopy illustrated spherical, uniform, and spongy microparticles. The developed micro formulation showed promising activity against the chosen acne bacterias and improved stability. Conclusion: The obtained results corroborate the premise that dapsone loaded microsponge gel can be an effective strategy for acne management.

Microsponges for controlled release and enhanced oral bioavailability of carbamazepine

The oral absorption and hence the oral bioavailability of carbamazepine (CBZ) is variable even after administration of rapidly dissolving formulation. This problem was attributed to supersaturation of CBZ and transformation to the less soluble carbamazepine dihydrate (CBD). Accordingly, formulation of sustained release products of CBZ is a promising approach to overcome this problem. Microsponges are an emerging formulation which can help in this direction. The aim of this work was to optimize the composition of microsponges for better encapsulation and sustained release of CBZ for oral administration. CBZ microsponges were prepared using quasi emulsion solvent diffusion technique with varying composition of ethyl cellulose and polyvinyl alcohol (PVA). Microsponges were evaluated using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction. Production yield, entrapment efficiency and surface morphology of microsponges were assessed in addition to drug release. Optimum formulation was administered orally to albino rabbits to evaluate the oral bioavailability with reference to unprocessed CBZ. The Instrumental analysis reflected the encapsulation of CBZ in amorphous or molecularly dispersed form in the microsponges. The size and entrapment efficiency of the microsponges increased with increasing polymer contents. This was associated with reduction in CBZ release. Optimum formulation enhanced the oral absorption of CBZ. This was manifested by 2.6-fold increase in the area under the plasma concentration versus time curve compared to that of unprocessed CBZ. The study introduced microsponges as promising carriers for sustained oral delivery of CBZ.

Development of a New Nanocarrier for Dietary Garcinol: Characterization and In Vitro Efficacy Evaluation Using Breast Cancer Stem Cells Grown in Hypoxia

Garcinol (GA), a polyisoprenylated benzophenone derivative, is one of the major phytochemicals found in a number of fruits of Garcinia. This study aimed to develop a new nanodelivery system comprising GA, hyaluronic acid (HA), and poly(lactic-co-glycolic acid) (PLGA) to actively target breast cancer stem cells (bCSCs) grown under hypoxic conditions. HA has been reported to show higher affinity for the cluster-determinant 44 receptor (CD44), while PLGA is an FDA-approved biodegradable polymer used in clinical applications. Nanoparticles (NPs) were prepared by emulsion solvent diffusion technique using DMAB as the emulsifier. Following preparation, particle size, surface charge, and polydispersity index of NPs were characterized. Antiproliferative effects of NPs were assessed by the WST-1 cell proliferation assay. Apoptotic effects of NPs were evaluated by the caspase-3/7 assay. Effects of prepared NPs on the expression of genes related to hypoxia-inducing factors (HIF-1α and HIF-2α) and notch ligands (DLL1 and Jagged1) were evaluated using real-time PCR. HA-coated garcinol-loaded NPs (HA-GA-NPs) showed greater antiproliferative effects in bCSCs grown under hypoxia. Moreover, HA-GA-NPs showed an improved cellular uptake via receptor-mediated endocytosis compared to non-HA-coated GA-NPs. Exposure to GA-HA-NPs resulted in a significant downregulation in hypoxia-inducing factors and notch pathway-related genes. Activation of caspase-3/7 confirmed the HA-GA-NPs can induce apoptosis in bCSCs. Overall findings of the study confirm that HA-GA-NPs can be considered as an effective nanodelivery system to target bCSCs grown under the hypoxic microenvironment.

Astaxanthin-Loaded Stealth Lipid Nanoparticles (AST-SSLN) as Potential Carriers for the Treatment of Alzheimer's Disease: Formulation Development and Optimization.

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with marked oxidative stress at the level of the brain. Recent studies indicate that increasing the antioxidant capacity could represent a very promising therapeutic strategy for AD treatment. Astaxanthin (AST), a powerful natural antioxidant, could be a good candidate for AD treatment, although its use in clinical practice is compromised by its high instability. In order to overcome this limit, our attention focused on the development of innovative AST-loaded stealth lipid nanoparticles (AST-SSLNs) able to improve AST bioavailability in the brain. AST-SSLNs prepared by solvent-diffusion technique showed technological parameters suitable for parenteral administration (<200 nm). Formulated nanosystems were characterized by calorimetric studies, while their toxicological profile was evaluated by the MTT assay on the stem cell line OECs (Olfactory Ensheathing Cells). Furthemore, the protective effect of the nanocarriers was assessed by a long-term stability study and a UV stability assay confirming that the lipid shell of the nanocarriers was able to preserve AST concentration in the formulation. SSLNs were also capable of preserving AST’s antioxidant capacity as demonstrated in the oxygen radical absorbance capacity (ORAC) assay. In conclusion, these preliminary studies outline that SSLNs could be regarded as promising carriers for systemic administration of compounds such as AST aimed at AD treatment.

Optimisation of PCL-HA laden biodegradable nanoparticles containing cyclosporine-A for the treatment of dry eye syndrome: in vitro-in vivo evaluation

The purpose of the present study is to develop polycaprolactone (PCL)-hyaluronic acid (HA) laden biodegradable nanoparticles containing cyclosporine-A (CsA) and sustained the release for ophthalmic delivery. The nanoparticles (NPs) were prepared by solvent diffusion technique followed lyophilisation. Optimisation of product variables for nanoparticles was done by central composite design (CCD) with particle size and entrapment efficiency as chosen responses. The developed formulation consisting 1.18% polycaprolactone and 0.16% hyaluronic acid showed 376.6 nm, −0.438 ± 0.137 mV and 40.945 ± 1.561% particle size, zeta potential and entrapment efficiency respectively. However, this formulation was efficient in controlling the drug release in-vitro as well, i.e., 92.59 ± 0.05% cyclosporine-A release at 24 hours. Surface morphology revealed nanoparticles were spherical in shape. Ocular irritancy study showed that formulation was safe and non-irritant. The Cmax of plain drug and biodegradable nanoparticles was found to be 15.802 mg at 6 hrs (mean residence time - MRT) and 19.447 mg at 8 hrs respectively. Area under the curve (AUC) was found to be 79.26 and 113.0 for plain drug and NPs formulation.

Mixed Micelles with Galactose Ligands for the Oral Delivery of Berberine to Enhance Its Bioavailability and Hypoglycemic Effects.

Diabetes mellitus (DM) has become an epidemic disorder that is an escalating public health risk. Currently, DM treatment is highly challenging due to temporary medical relief rather than a permanent cure. This article reports a ligand-anchored mixed micellar system formed by phospholipids and N -oleoyl-D-galactosamine aiming to enhance the oral bioavailability and hypoglycemic effects of berberine, an antidiabetic agent with poor absorption. Berberine-loaded mixed micelles (BBMMs) were prepared through a solvent diffusion technique. The resulting BB-MMs were characterized by particle size, potential, morphology, entrapment efficiency (EE) and in vitro release. The oral pharmacokinetics and hypoglycemic efficacy of BB-MMs were evaluated in rats and compared with a berberine suspension. As a result, BB-MMs prepared with the preferable formulation had a particle size of approximately 100 nm with an EE of over 85%. BB-MMs exhibited sustained drug release owing to the entrapment in the micelles. After oral administration, BB-MMs ameliorated the pharmacokinetic profile of berberine and significantly enhanced its oral bioavailability (317.17% relative to the suspension). The pharmacological effect (PE) of BB-MMs was approximately 3.44 times greater than that of the suspension. In addition, in situ single-pass intestinal perfusion and cellular testing results illustrated that BB-MMs had good intestinal permeability and cellular uptake. Our findings demonstrate that the oral bioavailability and hypoglycemic effects of berberine could be largely enhanced by encapsulation into mixed micelles with a galactose moiety. Thus, galactosylated micelles may be promising for developing berberine nanomedicines to fight DM.

Quercetin Covalently Linked Lipid Nanoparticles: Multifaceted Killing Effect on Tumor Cells.

The encapsulation of hydrophobic drugs is a problem that many researchers are working on. The goal of this study is to achieve the delivery of hydrophobic drugs by means of prodrugs and nanoformulations for a stronger tumor cell-killing effect and explore related killing mechanisms. Lipophilic quercetin (Qu) was covalently linked to glyceryl caprylate-caprate (Gcc) via disulfide bonds-containing 3,3′-dithiodipropionic acid (DTPA) to synthesize novel lipid Qu-SS-Gcc. Qu-SS-Gcc lipid nanoparticles (Qu-SS-Gcc LNPs) were fabricated using the solvent diffusion technique. The intracellular release of Qu by cleavage of nanocarriers was determined by liquid chromatography and compared with the uptake of free Qu. Detection methods, such as fluorescent quantitation, flow cytometry, and western blot were applied to explore the action mechanism induced by Qu. It was revealed that Qu-SS-Gcc LNPs could be cleaved by the high concentrations of reduction molecules in MCF-7/ADR (human multidrug-resistant breast cancer) cells, followed by the release of Qu. The intracellular Qu content produced by dissociation of Qu-SS-Gcc LNPs was higher than that produced by internalization of free Qu. The resulting release of Qu exerted superior cell-killing effects on MCF-7/ADR cells, such as P-gp inhibition by binding to P-gp binding sites, blocking the cell cycle in the G2 phase, and causing cell apoptosis and autophagy. Moreover, it was revealed autophagy triggered by a low concentration of Qu-SS-Gcc LNPs was beneficial to cell survival, while at a higher concentration, it acted as a cell killer. Qu-SS-Gcc LNPs can realize massive accumulation of Qu in tumor cells and exert a multifaceted killing effect on tumor cells, which is a reference for the delivery of hydrophobic drugs.

Polymeric Inserts Containing Eudragit® L100 Nanoparticle for Improved Ocular Delivery of Azithromycin.

Polymeric inserts containing azithromycin-loaded Eudragit® L100 nanoparticles were developed to sustain the drug release and enhance its ocular performance. The solvent diffusion technique was employed to prepare nanoparticles. The developed nanoparticles (NPs) were fully characterized and investigated. The solvent casting method was used to prepare azithromycin ocular inserts (azithromycin, AZM film) by adding hydroxypropyl methylcellulose (HPMC) or hydroxyethyl cellulose (HEC) solutions after the incorporation of AZM-loaded Eudragit® L100 nanoparticles into plasticized PVA (polyvinyl alcohol) solutions. The optimized nanoparticles had a particle size of 78.06 ± 2.3 nm, zeta potential around −2.45 ± 0.69 mV, polydispersity index around 0.179 ± 0.007, and entrapment efficiency 62.167 ± 0.07%. The prepared inserts exhibited an antibacterial effect on Staphylococcus aureus and Escherichia coli cultures. The inserts containing AZM-loaded nanoparticles showed a burst release during the initial hours, followed by a sustained drug release pattern. Higher cumulative corneal permeations from AZM films were observed for the optimized formulation compared to the drug solution in the ex-vivo trans-corneal study. In comparison to the AZM solution, the inserts significantly prolonged the release of AZM in rabbit eyes (121 h). The mucoadhesive inserts containing azithromycin-loaded Eudragit® L100 nanoparticles offer a promising approach for the ocular delivery of azithromycin (antibacterial and anti-inflammatory) to treat ocular infections that require a prolonged drug delivery.