Percent Drug Loading Research Articles

Lovastatin Loaded Solid lipid nanoparticles for Transdermal delivery: In vitro Characterization

Lovastatin-loaded solid lipid nanoparticles were prepared by using glyceryl monostearate as lipid by solvent emulsification diffusion technique. The prepared SLNs were evaluated for particle size, shape, polydispersity index,zeta potential, percent drug loading, and in vitro release profile.The results reveal that the optimized SLNs are spherical, with a smooth surface and having particle size 298±1.1 nm, the PDI and zeta potential of optimized formulation was 0.42±0.09 and -19.1±0.81 MeV, respectively, the percent drug loading was 49.81±0.87. The optimized formulation follows Higuchi’s kinetics for drug release.

The discovery of berberine erythrocyte-hemoglobin self-assembly delivery system: a neglected carrier underlying its pharmacokinetics

Berberine (BBR) has extremely low concentration and high tissue distribution. However, current pharmacokinetic studies predominantly focus on its concentration in plasma, which could hardly make a comprehensive understanding of its pharmacokinetic process. This study made a pioneering endeavor to explore the erythrocyte-hemoglobin (Hb) self-assembly system of BBR by exploring the interaction of BBR with erythrocyte and the combination of BBR with Hb. Results showed that BBR had a low bioavailability (C0 = 2.833 μg/mL via intravenous administration of 2.5 mg/kg BBR and Cmax = 0.260 μg/mL via oral administration of 400 mg/kg BBR). Besides, BBR achieved higher concentrations in erythrocytes than plasma, and the erythrocytes count and Hb content were significantly decreased after intravenous administration. Hemolysis rate indicated the BBR-erythrocyte system (with 2% erythrocytes) was relatively stable without hemolysis at the concentration of 1.00 mg/mL. And the maximum percentage of drug loading was 100% when the BBR-erythrocyte concentration was 0.185 μg/mL. Furthermore, incubation of BBR and erythrocytes resulted in internalization of the erythrocyte membrane and the formation of intracellular vacuoles. The thermodynamic parameters indicated that the binding process of bovine hemoglobin (BHB) and BBR was spontaneous. UV-vis absorption spectra, synchronous fluorescence, circular dichroism and Raman spectra collectively indicated that BBR showed strong binding affinity toward BHB and affected the molecular environment of residues like tryptophan and tyrosine in BHB, resulting in the conformational changes of its secondary and tertiary structure. Molecular docking indicated BBR interacted with Arg-141 residue of BHB via hydrogen bond with the bond length of 2.55 Å. The ΔG value of the BHB-BBR system was −31.79 kJ/mol. Molecular dynamics simulation indicated the root mean square derivation of BBR-BHB was <0.025 nm, suggestive of stable conformation. Cumulatively, there was an erythrocyte-Hb self-assembled drug delivery system after oral or intravenous administration of BBR, which conceivably gained novel insight into the discrepancy between the extremely low plasma concentration and relatively high tissue concentration of BBR.

Box-Behnken design optimized silibinin loaded glycerylmonooleate nanoliquid crystal for brain targeting

Silibinin (SIL) is a neuroprotective and amyloid aggregate inhibitor that showed therapeutic applications in preclinical studies of Alzheimer’s disease (AD). Due to poor aqueous solubility free SIL is unable to reach the brain after oral administration. Therefore SIL was encapsulated in nano-liquid crystals (NLCs) to increase payload in brain using glyceryl monooleate (GMO). The NLCs were prepared through the emulsification and probe sonication method. The optimization of SIL-NLCs was done using Box-Behnken design (BBD). BBD investigated the effect of independent variable such as GMO weight, pluronics-127 (PF-127) concentration, and sonication time on critical quality attributes such as particle size and percentage drug loading (%DL) for enhancement of drug availability at targeted site. The particle size of SIL-NLCs optimized by BBD was found to be 113.2 ± 3.3 nm particle size and 8.02 ± 0.4% DL. The FTIR and DSC characterization of SIL-NLCs showed SIL is dispersed in the GMO matrix in the amorphous form. TEM analysis confirmed the cubical and crystal-like shape of the NLCs having particle size less than 150 nm. After single oral gavage of a 30 mg/kg dosage of SIL in Wistar rats, the pharmacokinetic investigations revealed that the amount of SIL available in plasma of animals administered with NLCs showed AUC0-∞ = 19.61 µg mL−1 h compared to free SIL group having AUC0-∞ = 6.72 µg mL−1 h (P > 0.005). Brain uptake studies showed SIL-NLCs treated groups have 2.25 µg/g availability of SIL compared to 10.02 µg/g for the free SIL group. The outcomes of this investigation are promising in terms of potential use of SIL-NLCs in further studies as well as using SIL for the treatment of AD.

In vitro release and cytotoxicity study of encapsulated sulfasalazine within LTSP micellar/liposomal and TSP micellar/niosomal nano-formulations

The micelles/liposome formulation for the first time has been constructed via thin-film hydration method containing soy lecithin (L), tween 80 (T), squalene (S), and polyvinyl alcohol (P) (LTSP nanoparticles). Similar ingredients except for lecithin were used for preparing micellar/niosomal vesicular SSZ nanoformulation (TSP nanoparticles). The percent drug loading and encapsulation efficiency of SSZ was 7.39% and 98.5 ± 0.3 % for the 7.5:100 (w/w) ratio of SSZ: total weight of LTSP, while the percent drug loading and encapsulation efficiency of SSZ was 4.7% and 62.85 ± 0.3 % in the TSP nanoformulation. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results showed that both formulations formed spherical micelles and vesicles with globule sizes of 25 ± 1.2 nm and 100 ± 20.5 nm respectively. The cell toxicity evaluations showed that both LTSP and TSP nanoformulations without drug were nontoxic (at the range of this experiment) for Human Dermal Fibroblasts (HDF) as a normal cell line but SSZ loaded nanoformulation exhibited increased cell toxicity with half-maximal inhibitory concentration (IC50) of 940 µM for SSZ alone to near 240 µM for SSZ loaded nanoformulation (approximately four times). In vitro release experiments exhibited sustained release of SSZ from both nanoformulations. The LTSP micellar/liposomal and TSP micellar/niosomal nanoformulation for SSZ delivery can be considered as appropriate approaches for improving its bioavailability and probably they are good candidates for future clinical investigations.

Nanosized paclitaxel-loaded niosomes: formulation, in vitro cytotoxicity, and apoptosis gene expression in breast cancer cell lines.

In this study, the optimized niosomal formulation containing paclitaxel using non-ionic surfactants and cholesterol was designed and its cytotoxic effects against different breast cancer cell lines and apoptosis gene expression analysis were also investigated. Due to enhancing equation variables, the Box-Behnken method has been applied. Lipid/drug molar ratio, the amounts of Span 60, and cholesterol were selected as the target for optimization. The particle size of niosome loaded paclitaxel and entrapment efficiency proportion have been considered in the role of dependent variables. Then the cytotoxic activity of the optimized formulation was evaluated using an MTT assay against different breast cancer cell lines including MCF-7, T-47D, SkBr3, and MDA-MB-231. The expression level of Bax and Bcl-2 apoptosis genes was determined by Real-Time PCR. In this study, the optimized niosomal formulation revealed that the synthesized niosomes had a spherical appearance and had an average size of 192.73 ± 5.50nm so that the percentage of drug loading was 94.71 ± 1.56%. Moreover, this formulation showed a controlled and slowed release of paclitaxel at different pH (7.4, 6.5, and 5.4). The cytotoxicity results demonstrated that cell viability in all concentrations of niosome loaded paclitaxel had profound cytotoxic effects on all studied breast cancer cell lines compared to the free paclitaxel (p < 0.05). In addition, the expression of apoptosis genes was much higher than that of free paclitaxel indicating the susceptibility of cells to apoptosis. As a result, niosomal formulations containing paclitaxel can be used as a new drug delivery system to increase cytotoxicity and treatment of breast cancer in the upcoming future.

Development of β-cyclodextrin/polyvinypyrrolidone-co-poly (2-acrylamide-2-methylpropane sulphonic acid) hybrid nanogels as nano-drug delivery carriers to enhance the solubility of Rosuvastatin: An in vitro and in vivo evaluation.

The present study is aimed at enhancing the solubility of rosuvastatin (RST) by designing betacyclodextrin/polyvinypyrrolidone-co-poly (2-acrylamide-2-methylpropane sulphonic acid) crosslinked hydrophilic nanogels in the presence of crosslinker methylene bisacrylamide through free-radical polymerization method. Various formulations were fabricated by blending different amounts of betacyclodextrin, polyvinylpyrrolidone, 2-acrylamide-2-methylpropane sulphonic acid, and methylene bisacrylamide. The developed chemically crosslinked nanogels were characterized by FTIR, SEM, PXRD, TGA, DSC, sol-gel analysis, zeta size, micromeritics properties, drug loading percentage, swelling, solubility, and release studies. The FTIR spectrum depicts the leading peaks of resultant functional groups of blended constituents while a fluffy and porous structure was observed through SEM images. Remarkable reduction in crystallinity of RST in developed nanogels revealed by PXRD. TGA and DSC demonstrate the good thermal stability of nanogels. The size analysis depicts the particle size of the developed nanogels in the range of 178.5 ±3.14 nm. Drug loading percentage, swelling, solubility, and release studies revealed high drug loading, solubilization, swelling, and drug release patterns at 6.8 pH paralleled to 1.2 pH. In vivo experiments on developed nanogels in comparison to marketed brands were examined and better results regarding pharmacokinetic parameters were observed. The compatibility and non-toxicity of fabricated nanogels to biological systems was supported by a toxicity study that was conducted on rabbits. Efficient fabrication, excellent physicochemical properties, improved dissolution, high solubilization, and nontoxic nanogels might be a capable approach for the oral administration of poorly water-soluble drugs.

Preparation of magnetic methotrexate nanocarrier coated with extracted hydroxyapatite of sea urchin (Echinometra mathaei)

New polymer-coated magnetic nanocarrier using magnetic iron oxide nanoparticles coated with chitosan and nanohydroxyapatite extracted from Sea urchin that both have anti-cancer properties showed good ability to Methotrexate (MTX) delivery. Iron oxide nanoparticles and hydroxyapatite prepared by co-precipitation and hydrothermal methods respectively. To stabilize the nanoparticles and optimization of the nanoparticles with hydroxyapatite, 3-chloropropyltrioethoxysilane and chitosan were performed. The water-soluble anticancer drug Methotrexate was selected as the drug model. The drug loading percentage was % 86.66, loading efficiency was % 99.5 and the polydispersity of the nanoparticles was 0.01. The kinetic pattern of drug release is consistent with the Peppas equation and the results of the thermal analysis confirm the stability of the crystalline form of the drug. The FTIR results and FE-SEM images showed that the nanoparticles were successfully prepared and coated and their size ranged from 30 nm to 1.5μm. The VSM analysis confirms the magnetic properties of the nanoparticles and the magnetic indices for the magnetic nanocarrier and the magnetic nanocarrier carrying MTX are 23 and 19 emu/g–1, respectively. The present study demonstrates the potential of iron oxide nanoparticles for the design of new magnetic nanocarrier and for guiding Methotrexate drug therapy in cancer chemotherapy.

A mucoadhesive biodissolvable thin film for localized and rapid delivery of lidocaine for the treatment of vestibulodynia

Vestibulodynia (VBD), an idiopathic pain disorder characterized by erythema and pain of the vulvar vestibule (the inner aspect of the labia minora and vaginal opening), is the most common cause of sexual pain for women of reproductive age. Women also feel discomfort with contact with clothing and tampon use. As most women with this disorder only have pain with provocation of the tissue, topical anesthetics applied to the vestibule are the current first line treatment for temporary pain relief. Treatment options are limited due to anatomical constraints of the vestibular region, poor drug retention time, imprecise dosing, leakage, and overall product messiness. In this study we report a novel approach to treatment of VBD using thin film designed to fit the vulvar vestibule and deliver lidocaine locally. Two use cases for VBD treatment were identified 1) rapid drug release (<5 min), for use prior to intercourse and 2) long-acting release (≥120 min) for prolonged use and relief throughout the day. Cellulose-based mucoadhesive thin films were fabricated using a solvent casting method. Three polymers including hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), and hydroxypropylmethycellulose (HMPC), were selected owing to their biocompatibility and ideal properties for film casting. Films casted with HEC, HPC, and HPMC exhibited mucoadhesive properties relative to a control, with the highest mucoadhesive force recorded for films casted with HPC. Effect of media volume, pH, presence of mucin and presence of drug on film dissolution rates were investigated. Dissolution rates were independent of media volume, media pH or drug presence, whereas faster dissolution rates were obtained for all films in presence of mucin. In vitro lidocaine release kinetics were influenced by polymer type, percent drug loading and film casting thickness. Lidocaine release was based on a diffusion mechanism rather than through film dissolution and faster release (∼5 min) was observed for HEC films compared HPC films (∼120 min). Higher drug loading and film thickness resulted in slower and more prolonged release kinetics of lidocaine. All films were biocompatible and exhibited good mechanical properties. Two film formulations (9% w/w HPC with 12% w/w LHC, 5% w/w HEC with 6% w/w LHC) were optimized to meet the two use case scenarios for VBD treatment and moved into in vivo testing. In vivo testing demonstrated the safety of the films in BALB/c mice, and the pharmacokinetic analysis demonstrated the delivery of lidocaine primarily to the vaginal tissue. We demonstrate the ability to develop a mucoadhesive, biodissolvable thin film and fine-tune drug release kinetics to optimize local delivery of lidocaine to the vulva.

Co-Loading of Temozolomide and Curcumin into a Calix[4]arene-Based Nanocontainer for Potential Combined Chemotherapy: Binding Features, Enhanced Drug Solubility and Stability in Aqueous Medium.

The co-delivery of anticancer drugs into tumor cells by a nanocarrier may provide a new paradigm in chemotherapy. Temozolomide and curcumin are anticancer drugs with a synergistic effect in the treatment of multiform glioblastoma. In this study, the entrapment and co-entrapment of temozolomide and curcumin in a p-sulfonato-calix[4]arene nanoparticle was investigated by NMR spectroscopy, UV-vis spectrophotometry, isothermal titration calorimetry, and dynamic light scattering. Critical micellar concentration, nanoparticle size, zeta potential, drug loading percentage, and thermodynamic parameters were all consistent with a drug delivery system. Our data showed that temozolomide is hosted in the cavity of the calix[4]arene building blocks while curcumin is entrapped within the nanoparticle. Isothermal titration calorimetry evidenced that drug complexation and entrapment are entropy driven processes. The loading in the calixarene-based nanocontainer enhanced the solubility and half-life of both drugs, whose medicinal efficacy is affected by low solubility and rapid degradation. The calixarene-based nanocontainer appears to be a promising new candidate for nanocarrier-based drug combination therapy for glioblastoma.

Development of pH-Sensitive Chitosan-g-poly(acrylamide-co-acrylic acid) Hydrogel for Controlled Drug Delivery of Tenofovir Disoproxil Fumarate.

The present study aimed to develop a pH-sensitive chitosan-based hydrogel for controlled delivery of an anti-hepatitis B drug, tenofovir disoproxil fumarate (TDF). Free radical polymerization was utilized to graft acrylamide and acrylic acid using N,N-methylene bisacrylamide as the crosslinker. Physicochemical characterization confirmed the synthesis of thermally stable chitosan-g-poly(acrylamide-co-acrylic acid) hydrogels with well-defined pores within a fibrous surface. The prepared hydrogels exhibited pH and ionic strength sensitivity, with the swelling significantly lower under acidic and strong ionic strength conditions but higher in neutral and basic solutions. In addition, cytotoxicity studies on HeLa cell lines proved the cytocompatibility of the drug delivery material and its readiness for physiological applications. The encapsulation of TDF in the hydrogels was optimized and an encapsulation efficiency and a drug loading percentage of 96% and 10% were achieved, respectively. More interestingly, in vitro release studies demonstrated a pH-dependent release of TDF from hydrogels. The release at pH 7.4 was found to be up to five times higher than at pH 1.2 within 96 h. This further suggested that the newly developed hydrogel-loaded TDF could be proposed as a smart delivery system for oral delivery of anti-hepatitis B drugs.

Development, optimization, and in vitro evaluation of atorvastatin calcium and vinpocetine codelivery by solid lipid nanoparticles for cancer therapy

BackgroundThe main objective of the present study was to formulate, optimize and characterize solid lipid nanoparticles (SLNs) loaded with Atorvastatin Calcium (ATS) and Vinpocetine (VIN) as a potential drug delivery system to improve its solubility and assess its anti-tumor activity on cell lines. The SLNs were formulated by emulsification with high speed homogenization followed by probe sonication. Central composite design was selected for optimization. Drug: lipid ratio, surfactant: co-surfactant ratio and homogenization speed were considered critical process parameters (CPP) to study the effects on critical quality attributes (CQA) of SLNs i.e. particle size, percent entrapment efficiency (% EE) and percent drug loading (% DL).ResultsThe optimized (F3) SLNs formulations were characterized by transmission electron microscopy (TEM), X- ray diffraction (X-RD), in vitro drug release by dialysis bag method and stability studies. In vitro cell line studies were performed on HepG2, MCF 7 and melanoma B16 F10 cell line. The optimized F3 formulation showed a particle size of 323 ± 6 nm, poly dispersity index (PDI) 0.333 ± 0.02, Zeta potential (ZP) − 30.4 ± 0.66 emv with % EE 64.69 ± 1.1; 65.98 ± 0.91 of ATS and VIN respectively. In vitro release (F3) of ATS and VIN in PBS pH 7.4 was found to be 89.45% and 91.86%, respectively, up to 24 h.ConclusionsIn vitro cell line study demonstrated that SLNs enhanced the anti-cancer activity of ATS, VIN on all the stated cell lines when compared with free drugs. Combination index (CI) for HEPG2 was 0.8, which signified synergistic effect. The results exhibited that SLNs is effective, stable and had enhanced activity against HepG2, MCF 7 and melanoma B16 F10 cell lines.

Colon targeted dosage form of Capecitabine using folic acid anchored modified carbon nanotube: in vitro cytotoxicity, apoptosis and in vivo roentgenographic study

Objective Development of dosage form comprising of Capecitabine loaded carbon nanotubes for its targeted delivery to the colon. Method Single walled carbon nanotubes (SWCNT) were functionalized by -COOH and Chitosan along with Folic acid. Capecitabine was loaded in these SWCNT’s, and the system was analyzed by FTIR, SEM and Raman spectroscopy. Percent drug loading was assessed and the cytotoxicity (COLO320DM and HT29) was verified by using MTT and SRB assay. The apoptosis study was carried out by flowcytometry. The system was enclosed in an enteric coated capsule with pH sensitive polymers and characterized for invitro disintegration, dissolution and invivo roentgenographic studies. Results FTIR, Raman and XRD studies indicated the confirmation of attachments, whereas SEM exhibited size range of 200-500 nm. Drug loading capacity was observed to be 94.63 ± 1.07%. Cytotoxicity studies of Capecitabine and FA–CHI-F-SWCNT-Capecitabine against COLO320DM by using MTT assay showed that FA–CHI-F-SWCNT- Capecitabine exhibited 86.45 ± 0.5788% inhibition whereas pure Capecitabine showed 50.52 ± 0.3106% inhibition. Against HT29, the % inhibition was observed to be 82.76 ± 0.4668% and 56.41 ± 0.2316% respectively for FA–CHI-F-SWCNT-Capecitabine and pure Capecitabine. In case of SRB assay of COLO320DM, the FA–CHI-F-SWCNT-Capecitabine exhibited 89.62 ± 0.4095% inhibition and Capecitabine showed 84.36 ± 0.2559% inhibition, whereas against HT29, FA–CHI-F-SWCNT-Capecitabine showed 81.36 ± 0.2958% inhibition and Capecitabine exhibited 90.62 ± 0.4196% inhibition. Conclusion FA–CHI-F-SWCNT loaded system revealed better cytotoxicity as compared with pure Capecitabine against two different cell lines. Invivo studies revealed that the prepared capsule formulation remained intact in the stomach thereby preventing drug release in the gastric milieu.

A novel and oral colon targeted isoliquiritigenin delivery system: Development, optimization, characterization and in vitro evaluation

The aims of the study were to prepare oral colon targeted gel beads loaded with isoliquiritigenin (ISL) which exhibited a variety of biological activities with a low solubility and oral bioavailability. ISL loaded sodium alginate and pectin gel beads (SA-P gel beads) were prepared by ionic gel technique, and Uniform Design method was used to optimize the formulation. To decrease the leakage in simulated gastric juice and simulated intestinal juice, the Eudragit S-100, sodium alginate and pectin gel beads (EU-SA-P gel beads) were prepared based on the SA-P gel beads. The EU-SA-P gel beads were characterized for size, shape, morphology, encapsulation efficiency, drug loading percentage, swelling degree and in vitro release. The size and shape results showed that the EU-SA-P gel beads were yellow and spherical with a size of 1.22 ± 0.19 mm, and a roundness degree of 72.78% ± 8.25%. It could be confirmed by DSC and FTIR analysis that the drug was not chemically modified but physically dispersed in the gel beads. The swelling degree of EU-SA-P gel beads in simulated gastric juice was 1.13 ± 0.14 at 3 h and remained almost unchanged until 6 h indicating the beads would not dissolve in simulated gastric juice. In simulated intestinal juice, the swelling degree reached the maximum (22.73 ± 3.27) at 3 h which was 20.11 times of that in simulated gastric juice and decreased to 1.85 ± 0.19 at 6 h indicating the gel beads swelled in simulated intestinal juice. As for in simulated colonic juice, the maximum swelling degree was 16.63 ± 3.52 at 3 h which was 0.73 times of that in simulated intestinal juice, then the swelling degree decreased to 1.93 ± 2.33 at 6 h indicating the beads dissolved in simulated colonic juice. The results of in vitro evaluation tests revealed that the cumulative drug release percentage of EU-SA-P gel beads exposure to simulated gastric juice and simulated intestinal juice was only 12.74% ± 3.55% for 5 h. However, the cumulative drug release percentage in simulated colonic juice was 50.64% ± 2.22% from 5 h to 12 h which was 3.97 times of that in pre-colon. These results revealed that the EU-SA-P gel beads was a promising isoliquiritigenin delivery system for colon targeting.

Preparation, characterization, and in vivo evaluation of Rose damascene extract loaded solid lipid nanoparticles for targeted brain delivery.

According to a variety of experiments, Rose damascene may lead to memory enhancement and acetylcholine esterase inhibition. However, Rose damascene cannot pass through the blood-brain barrier due to its hydrophilic contents. Solid lipid nanoparticles (SLNs) are suitable carriers for brain drug delivery. Herein, SLNs were made by micro-emulsion method. Then, lactoferrin was covalently attached to the surface of the nanoparticles by amide bond interaction for targeted delivery. The nanoparticle properties and the amount of attached lactoferrin were calculated. The effect of the selected compounds on scopolamine-induced animals was also measured by Y-maze, passive avoidance test, elevated plus maze, and forced swim test. The results revealed that the size and zeta potential of nanoparticles were 52 nm and - 13 mV before conjugation, and 161 nm and - 16 mV after conjugation, respectively. The percentage of entrapment efficiency and drug loading before conjugation was 98 ,93.6 and, after conjugation, was 11.2, 15.9, respectively. According to Y-maze and passive avoidance test results, Rose damascene can enhance short-term memory and may also reduce anxiety and depression in scopolamine-induced animals.

Chronomodulated Drug Delivery System of Salmeterol Fluticasone Nlcs Loaded Tablets: Preparation, Characterization, Stability and Drug Release Studies for Management of Asthma

Objective: The purpose of this study was to develop salmeterol, fluticasone nano-lipid carriers to estimate as potentials of oral delivery system for poorly water soluble drugs. Nano-lipid carriers applied to chronomodulated pulsatile drug delivery system maintain the concentration level by releasing the drug at predetermined time interval throughout the management of asthma. Method: The particle size analysis revealed that all the formulations were within the nanometer range of 150.0±2.4nm. Percentage of entrapment efficiency and drug loading were found to be 69.5±4.4 - 85.3±1.3 and 9.358±2.2-10.45±8.1, respectively. The SLM-FCN nano-lipid carrier’s optimized formulation showed spherical morphology with smooth surface under the transmission electron microscope (TEM), the crystalline characterization of drug in NLC was investigated by X-ray diffraction and differential scanning calorimetric (DSC). The ex-vivo permeation study showed many folds increment in the SLM-FCN NLCs compared to powder SLM-FCN 96.0±2.55 and pulsing plugs in-vivo drug released effectively in pre-determine time intervals. Conclusion: The progression concludes that chronomodulated programming pulsatile release was achieved with modified pulsing bilayerd plugged of salmeterol, fluticasone propionate NLCs, formulation remarkably improved oral bioavailability. we promise that finding in this investigations suggest practicability of the dosage form system can be taken after at bedtime then it will be delivered in the early morning which maintains the drug concentration throughout to control asthma.

Electrostatic deposition assisted preparation, characterization and evaluation of chrysin liposomes for breast cancer treatment

Chrysin (CHR), a flavone found in multiple vegetables, fruits and mushrooms has been explored so far as a neurotropic, anti-inflammatory and anti-cancer biomolecule. Despite the stated therapeutic potential, low solubility and bioavailability limit its therapeutic benefit. To circumvent these drawbacks, development of chrysin liposomes (CLPs) is reported in the present investigation. The CLPs were developed by electrostatic deposition assisted film hydration method using chitosan/lecithin to protect chrysin in the nano-lipoidal shell. Developed CLPs were extensively characterized by DSC, XPRD, FE-SEM, TEM, particle size, polydispersity index, zeta potential, percent drug loading and encapsulation efficiency. These CLPs were further characterized by in vitro dissolution, in vivo bioavailability, in vitro anticancer and stability study. Suitable particle size, PDI and ZP implying stabilization of developed CLPs. The % DL and % EE was found to be 3.56 ± 0.13 and 90.5 ± 1.49 respectively. DSC and PXRD study revealed amorphous transition of CHR, which may help to increase its solubility and dissolution profile. In vivo pharmacokinetic study demonstrated more than 5-fold increase in relative bioavailability of CLPs. The in silico molecular docking study results demonstrated the electrostatic interaction between two polymers. The present study suggests that chitosan could protect and encapsulate chrysin which eventually enhances its cytotoxicity as well as bioavailability.

Development of Intranasal Levothyroxine Powder Delivery for Hypothyroidism

Background: Hypothyroidism affects 3-5% of the general population with oral levothyroxine (LT4) being the predominant replacement therapy. However, significant proportion of hypothyroid patients are unable to absorb oral replacement leading to therapeutic failure and may require injectable thyroxine. Objectives: To develop non-invasive, less costly, and patient-friendly LT4 nasal delivery alternative using mucoadhesive polymers: chitosan and hydroxypropylmethylcellulose (HPMC). Methods: Six nasal LT4 formulations were developed with either chitosan or hydroxypropyl methylcellulose as mucoadhesive. The formulations were prepared through freeze-drying by varying the drug to polymer ratio (1:1, 1:3, and 1:5). The percentage drug yield was calculated by analyzing the weight of the formulation pre- and post-freeze drying. HPLC analysis was conducted to determine the amount of LT4 loaded in each formulation. Furthermore, the surface morphology, particle size, zeta potential, differential scanning calorimetry, X-ray diffraction as well as the in vitro release were assessed to determine the physicochemical properties and release characteristics of the formulations, respectively. Results: Both percentage drug loading and yield were > 70% for all the formulations. The freeze-dried formulations displayed a compact needle-like surface morphology. LT4-chitosan formulations, 1:1, 1:3, and 1:5 had mean particle size of 2.45 ± 0.88 µm, 2.76 ± 1.38 µm, and 1.59 ± 0.27 µm, respectively. Mean particle sizes for 1:1, 1:3, and 1:5 LT4-HPMC formulations were 0.56 ± 0.02 µm, 0.22 ± 0.06 µm, and 0.46 ± 0.04 µm. Zeta potential for LT4-chitosan formulation 1:1, 1:3, and 1:5 were -18.7 ± 1.00 mV, -16.2 ± 0.79 mV, and -19.17 ± 1.01 mV, respectively. LT4-HPMC 1:1, 1:3, and 1:5 formulations had zeta charges of -11.66 ± 3.16 mV, -6.06 ± 3.92 mV, and -9.53 ± 1.68 mV, respectively. Differential calorimetric analysis confirmed drug-polymer integration in all formulations, and X-ray powder diffraction showed both chitosan and HPMC formulations as crystalline configuration. The formulations with the highest in vitro release were LT4-HPMC 1:3 and LT4-chitosan 1:5. Conclusions: Results of this study suggest that both chitosan and HPMC can be used as sustained release polymers for the intranasal delivery of LT4.

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies.

Solid lipid nanoparticles (SLNs) are being extensively exploited as topical ocular carrier systems to enhance the bioavailability of drugs. This study investigated the prospects of drug-loaded SLNs to increase the ocular permeation and improve the therapeutic potential of clarithromycin in topical ocular therapy. SLNs were formulated by high-speed stirring and the ultra-sonication method. Solubility studies were carried out to select stearic acid as lipid former, Tween 80 as surfactant, and Transcutol P as cosurfactant. Clarithromycin-loaded SLN were optimized by fractional factorial screening and 32 full factorial designs. Optimized SLNs (CL10) were evaluated for stability, morphology, permeation, irritation, and ocular pharmacokinetics in rabbits. Fractional factorial screening design signifies that the sonication time and amount of lipid affect the SLN formulation. A 32 full factorial design established that both factors had significant influences on particle size, percent entrapment efficiency, and percent drug loading of SLNs. The release profile of SLNs (CL9) showed ~80% drug release in 8 h and followed Weibull model kinetics. Optimized SLNs (CL10) showed significantly higher permeation (30.45 μg/cm2/h; p < 0.0001) as compared to control (solution). CL10 showed spherical shape and good stability and was found non-irritant for ocular administration. Pharmacokinetics data demonstrated significant improvement of clarithromycin bioavailability (p < 0.0001) from CL10, as evidenced by a 150% increase in Cmax (~1066 ng/mL) and a 2.8-fold improvement in AUC (5736 ng h/mL) (p < 0.0001) as compared to control solution (Cmax; 655 ng/mL and AUC; 2067 ng h/mL). In summary, the data observed here demonstrate the potential of developed SLNs to improve the ocular permeation and enhance the therapeutic potential of clarithromycin, and hence could be a viable drug delivery approach to treat endophthalmitis.

The PLGA Microspheres Synthesized by a Thermosensitive Hydrogel Emulsifier for Sustained Release of Risperidone

Risperidone is an important antipsychotic agent used for treatment of both acute and chronic schizophrenia. The drug has been effective in resolving the disease’s signs while keeping extrapyramidal side effects as low as possible. To achieve a sustained and gradual release of risperidone from PLGA microspheres, we utilized an emulsifying agent; PLGA-PEG-PLGA triblock (M-triblock), instead of PVA (M-PVA), applying ring-opening polymerization of the triblock via supercritical carbon dioxide (scCO2). PVA and PLGA-PEG-PLGA (as emulsifiers) were successfully employed to prepare risperidone-loaded PLGA microspheres. The scCO2 and microwave irradiation methods were used to construct PLGA-PEG-PLGA copolymers. The microspheres were subjected to various analyses to determine the particles’ sizes, morphological characteristics, and structure (via XRD) and in vitro drug release kinetics. Drug loading capacity and encapsulation percentage were also determined. The results showed a mean diameter of 43.34 ± 2.30 µm for M-PVA, and that of the M-triblock was 57.49 ± 1.21 µm. Risperidone encapsulation percentages were 72.8 ± 2.09 for M-PVAs and 73.4 ± 2.41 for the M-triblock. Particle size, risperidone distribution, and drug loading and encapsulation percentages were similar between M-PVAs and the M-triblock. In scanning electron microscopy (SEM), the morphology of the triblock emulsifier was more uniform than PVAs. The triblock emulsifier showed slower initial drug release than PVAs due to the precipitation of the triblock hydrogel around PLGA microspheres. Overall, the triblock used here can be a good alternative to PVA.

Native and Modified Oryza glaberrima Steud Starch Nanocrystals: Solid-state characterization and Anti-tumour drug release studies

In a bid to explore new biodegradable sourced materials for drug delivery, Oryza glaberrima starch was extracted, modified, and characterized. Nanocrystalstarch (NS) and acetylated nanocrystal starch (ANS) were produced from the native starch (S). The physicochemical properties, scanning electron microscopy(SEM), X-ray diffraction (XRD), Differential scanning calorimetry (DSC) and Fourier Transform Infra-red spectroscopy (FTIR) were done. The loading and release studies of Doxorubicin-loaded starches were carried out. The density, solubility, swelling capacity, and hydration capacity of the starch increased after modification whereas the amylose content was reduced. SEM revealed no change in morphology with sizes of the starch granules to be 5-15µm and the shape to be polyhedral. Modification of the starch increased the percentage drug loading capacity (DLC) and loading efficiency (LE). The drug release kinetics of the Dox-loaded S and ANS was the first-order release, while Dox-loaded NS was Korsemeyer-Peppas model. Improvement in the physicochemical properties of the NS and ANS made them useful carriers to sustain and control drug release.