scholarly journals A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy

Pharmaceutics ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 413 ◽  
Author(s):  
Hsiu-Chao Lin ◽  
Madonna Rica Anggelia ◽  
Chih-Chi Cheng ◽  
Kuan-Lin Ku ◽  
Hui-Yun Cheng ◽  
...  
Keyword(s):  
Immunosuppressive Therapy ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Immunosuppressive Agent ◽  
Sustained Delivery ◽  
Thermosensitive Hydrogel ◽  
Thermosensitive Hydrogels ◽  
Hydrogel System

Tacrolimus is an immunosuppressive agent for acute rejection after allotransplantation. However, the low aqueous solubility of tacrolimus poses difficulties in formulating an injection dosage. Polypeptide thermosensitive hydrogels can maintain a sustained release depot to deliver tacrolimus. The copolymers, which consist of poloxamer and poly(l-alanine) with l-lysine segments at both ends (P–Lys–Ala–PLX), are able to carry tacrolimus in an in situ gelled form with acceptable biocompatibility, biodegradability, and low gelling concentrations from 3 to 7 wt %. By adding Pluronic F-127 to formulate a mixed hydrogel system, the drug release rate can be adjusted to maintain suitable drug levels in animals with transplants. Under this formulation, the in vitro release of tacrolimus was stable for more than 100 days, while in vivo release of tacrolimus in mouse model showed that rejection from skin allotransplantation was prevented for at least three weeks with one single administration. Using these mixed hydrogel systems for sustaining delivery of tacrolimus demonstrates advancement in immunosuppressive therapy.

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

scholarly journals PLGA NANOPARTICLES LOADED MUCOADHESIVE AND THERMOSENSITIVE HYDROGEL AS A POTENTIAL PLATFORM FOR THE TREATMENT OF ORAL MUCOSITIS

2019 ◽  
Vol 11 (1) ◽  
pp. 106
Author(s):  
Gina S. El-feky ◽  
Gamal M. Zayed
Keyword(s):  
Oral Mucositis ◽  
In Vitro Release ◽  
Methyl Cellulose ◽  
Plga Nanoparticles ◽  
Complete Healing ◽  
Drug Release Profile ◽  
Thermosensitive Hydrogel ◽  
Hydrogel Matrix

Objective: The objective of this study was to design an effective topical treatment for oral mucositis.Methods: Poly-(DL-lactide-co-glycolide) (PLGA) nanoparticles (NPs) and Poloxamer407 (PLX)/Hydroxy propyl methyl cellulose (HPMC) hydrogel matrix (HG) were used as combined carriers for benzydamine HCL (BNZ). BNZ loaded PLGA nanoparticles were assessed for their particle size, PDI, zeta potential and entrapment efficiency. Scanning electron microscopy, thermosensitivity study, mucoadhesion study, in vitro release and in vivo investigation were used to characterize the combined BZN loaded PLGA NPs HG.Results: Negatively charged NPs with an average diameter of 139±4.92 nm were incorporated into PLX/HPMC HG bases. The gelation temperature of BZN-PLGA-NPs-HGs ranged between 31°C and 36.5°C. When diluted with saliva simulated fluid, BZN-PLGA-NPs-HGs preserved their gelation properties. Mucoadhesion was found lower for formulations prepared with PLX without HPMC. An increase in the concentrations of PLX from 10 to 30% resulted in an increase in adhesion. Both PLGA-NPs and PLGA-NPs-HG provided a biphasic drug release profile while BZN-HG provided monophasic zero order release pattern. The in vivo study showed that animal groups treated with BZN-HG and BZN-PLGA-NPs-HG showed a significantly higher reduction percentage in ulcer surface area compared to those treated with BZN-PLGA-NPs. BZN-PLGA-NPs-HG group needed 10 d of treatment to complete healing versus 16 d, 14 d and 12 d for the complete healing of groups with no treatment, treated with BZN-PLGA-NPs and treated with BZN-HG, respectively.Conclusion: BZN-PLGA-NPs-HG could represent a promising mean for the effective treatment of oral mucositis induced by cancer therapy.

scholarly journals Enhancement of Curcumin Anti-Inflammatory Effect via Formulation into Myrrh Oil-Based Nanoemulgel

Polymers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 577 ◽  
Author(s):  
Wafaa E. Soliman ◽  
Tamer M. Shehata ◽  
Maged E. Mohamed ◽  
Nancy S. Younis ◽  
Heba S. Elsewedy
Keyword(s):  
Ex Vivo ◽  
Skin Permeation ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Delivery Methods ◽  
Anti Cancer ◽  
Permeation Studies ◽  
Anti Inflammatory

Background: Curcumin (Cur) possesses a variety of beneficial pharmacological properties including antioxidant, antimicrobial, anti-cancer and anti-inflammatory activities. Nevertheless, the low aqueous solubility and subsequent poor bioavailability greatly limits its effectiveness. Besides, the role of myrrh oil as an essential oil in treating inflammatory disorders has been recently demonstrated. The objective of the current investigation is to enhance Cur efficacy via developing Cur nanoemulgel, which helps to improve its solubility and permeability, for transdermal delivery. Methods: The formulated preparations (Cur gel, emulgel and nanoemulgel) were evaluated for their physical appearance, spreadability, viscosity, particle size, in vitro release and ex vivo drug permeation studies. The in vivo anti-inflammatory activity was estimated using the carrageenan-induced rat hind paw edema method. Results: The formulated Cur-loaded preparations exhibited good physical characteristics that were in the acceptable range of transdermal preparations. The release of Cur from gel, emulgel and nanoemulgel after 12 h was 72.17 ± 3.76, 51.93 ± 3.81 and 62.0 ± 3.9%, respectively. Skin permeation of Cur was significantly (p < 0.05) improved when formulated into nanoemulgel since it showed the best steady state transdermal flux (SSTF) value (108.6 ± 3.8 µg/cm2·h) with the highest enhancement ratio (ER) (7.1 ± 0.2). In vivo anti-inflammatory studies proved that Cur-loaded nanoemulgel displayed the lowest percent of swelling (26.6% after 12 h). Conclusions: The obtained data confirmed the potential of the nanoemulgel dosage form and established the synergism of myrrh oil and Cur as an advanced anti-inflammatory drug.

scholarly journals Optimisation of a Microfluidic Method for the Delivery of a Small Peptide

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1505
Author(s):  
Felicity Y. Han ◽  
Weizhi Xu ◽  
Vinod Kumar ◽  
Cedric S. Cui ◽  
Xaria Li ◽  
...  
Keyword(s):  
Half Life ◽  
Drug Loading ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
The Body ◽  
Related Factors ◽  
Elimination Half ◽  
Therapeutic Peptides

Peptides hold promise as therapeutics, as they have high bioactivity and specificity, good aqueous solubility, and low toxicity. However, they typically suffer from short circulation half-lives in the body. To address this issue, here, we have developed a method for encapsulation of an innate-immune targeted hexapeptide into nanoparticles using safe non-toxic FDA-approved materials. Peptide-loaded nanoparticles were formulated using a two-stage microfluidic chip. Microfluidic-related factors (i.e., flow rate, organic solvent, theoretical drug loading, PLGA type, and concentration) that may potentially influence the nanoparticle properties were systematically investigated using dynamic light scattering and transmission electron microscopy. The pharmacokinetic (PK) profile and biodistribution of the optimised nanoparticles were assessed in mice. Peptide-loaded lipid shell-PLGA core nanoparticles with designated size (~400 nm) and a sustained in vitro release profile were further characterized in vivo. In the form of nanoparticles, the elimination half-life of the encapsulated peptide was extended significantly compared with the peptide alone and resulted in a much higher distribution into the lung. These novel nanoparticles with lipid shells have considerable potential for increasing the circulation half-life and improving the biodistribution of therapeutic peptides to improve their clinical utility, including peptides aimed at treating lung-related diseases.

scholarly journals Chitosan/Pluronic F127 Thermosensitive Hydrogel as an Injectable Dexamethasone Delivery Carrier

Gels ◽  
2022 ◽  
Vol 8 (1) ◽  
pp. 44
Author(s):  
Jomarien García-Couce ◽  
Miriela Tomás ◽  
Gastón Fuentes ◽  
Ivo Que ◽  
Amisel Almirall ◽  
...  
Keyword(s):  
Crosslinking Agent ◽  
Pluronic F127 ◽  
In Vivo Studies ◽  
Thermosensitive Hydrogel ◽  
Fluorescent Compound ◽  
Thermosensitive Hydrogels ◽  
Delivery Platform ◽  
Inflammatory Drugs

Intra-articular administration of anti-inflammatory drugs is a strategy that allows localized action on damaged articular cartilage and reduces the side effects associated with systemic drug administration. The objective of this work is to prepare injectable thermosensitive hydrogels for the long-term application of dexamethasone. The hydrogels were prepared by mixing chitosan (CS) and Pluronic-F127 (PF) physically. In addition, tripolyphosphate (TPP) was used as a crosslinking agent. Chitosan added to the mix increased the gel time compared to the pluronic gel alone. The incorporation of TPP into the material modified the morphology of the hydrogels formed. Subsequently, MTS and Live/Dead® experiments were performed to investigate the toxicity of hydrogels against human chondrocytes. The in vitro releases of dexamethasone (DMT) from CS-PF and CS-PF-TPP gels had an initial burst and took more time than that from the PF hydrogel. In vivo studies showed that hydrogels retained the fluorescent compound longer in the joint than when administered in PBS alone. These results suggest that the CS-PF and CS-PF-TPP hydrogels loaded with DMT could be a promising drug delivery platform for the treatment of osteoarthritis.

scholarly journals Iron Complexation to Histone Deacetylase Inhibitors SAHA and LAQ824 in PEGylated Liposomes Can Considerably Improve Pharmacokinetics in Rats

2015 ◽  
Vol 17 (4) ◽  
pp. 583 ◽  
Author(s):  
Yan Wang ◽  
Sheng Tu ◽  
Dana Steffen ◽  
May Xiong
Keyword(s):  
Encapsulation Efficiency ◽  
Histone Deacetylase Inhibitors ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Pegylated Liposomes ◽  
Pharmacokinetic Properties ◽  
Fe Complexes ◽  
Vitro Release

PURPOSE. The formulation of histone deacetylase inhibitors (HDACi) is challenging due to poor water solubility and rapid elimination of drugs in vivo. This study investigated the effects of complexing iron (Fe3+) to the HDACi suberoylanilide hydroxamic acid (SAHA) and LAQ824 (LAQ) prior to their encapsulation into PEGylated liposomes, and investigated whether this technique could improve drug solubility, in vitro release and in vivo pharmacokinetic (PK) properties. METHODS. The reaction stoichiometry, binding constants and solubility were measured for Fe complexes of SAHA and LAQ. The complexes were passively encapsulated into PEGylated liposomes and characterized by size distribution, zeta-potential, encapsulation efficiency (EE), and in vitro drug release studies. PC-3 cells were used to verify the in vitro anticancer activity of the formulations. In vivo pharmacokinetic properties of liposomal LAQ-Fe (L-LAQ-Fe) was evaluated in rats. RESULTS. SAHA and LAQ form complexes with Fe at 1:1 stoichiometric ratio, with a binding constant on the order of 104 M-1. Fe complexation improved the aqueous solubility and the liposomal encapsulation efficiency of SAHA and LAQ (29-35% EE, final drug concentration > 1 mM). Liposomal encapsulated complexes (L-HDACi-Fe) exhibited sustained in vitro release properties compared to L-HDACi but cytotoxicity on PC-3 cells was comparable to free drugs. The PK of L-LAQ-Fe revealed 15-fold improvement in the plasma t1/2 (12.11 h)and 211-fold improvement in the AUC∞ (105.7 µg·h/ml) compared to free LAQ (0.79 h, 0.5 µg·h/ml). Similarly, the plasma t1/2 of Fe was determined to be 11.83 h in a separate experiment using radioactive Fe-59. The majority of Fe-59 activity was found in liver and spleen of rats and correlates with liposomal uptake by the mononuclear phagocyte system. CONCLUSIONS. We have demonstrated that encapsulation of Fe complexes of HDACi into PEGylated liposomes can improve overall drug aqueous solubility, in vitro release and in vivo pharmacokinetic properties. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Preparation and Evaluation of Quercetin-Loaded MPEG-PLA Nanoparticles

2018 ◽  
Vol 14 (5) ◽  
pp. 366-376 ◽  
Author(s):  
Hiraku Onishi ◽  
Masashi Nakamura ◽  
Masanaho Sasatsu
Keyword(s):  
Organic Solvent ◽  
Therapeutic Potential ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
The Body ◽  
In Vivo Studies ◽  
Water Mixture ◽  
Biodistribution Studies

Background: Quercetin (QE) is one of the flavonoids with various biological functions such as anti-oxidation, anti-inflammatory and antitumor. However, the low aqueous solubility and short half-life in the body reduce its in vivo efficacy. Therefore, the appropriate delivery techniques to solve those problems have drawn much attention. In the present study, methoxypolyethylene glycol- poly-DL-lactic acid (MPEG-PLA) nanoparticles loaded with quercetin (QE), called NP, were prepared, and their antitumor characteristics were investigated in vitro and in vivo. Method: NPs were produced by evaporating organic solvent from the organic solvent-water mixture in four formulations. The particle characteristics and in vitro release were examined for the obtained preparations (NP1 – NP4). The antitumor features were investigated in vivo with different administration schedules using mice inoculated subcutaneously with murine Sarcoma 180. In addition, the efficacy of co-administration of NP with a strong antitumor chemotherapeutic agent, irinotecan hydrochloride (CPT-11), was examined. Biodistribution studies were performed using the same animal models. Result: The NP with the higher drug content (0.58 % (w/w)) and gradual release profile, Preparation NP4, were chosen and used as NP in the in vivo studies. NP suppressed tumor growth better than QE solution in various dosing schedules (total dose = 2 mg/kg). In the combination therapy with CPT-11, NP exhibited antitumor efficacy in a nearly additive manner. No decrease in body weight observed with any administration. NP markedly enhanced the systemic distribution and tumor localization. Conclusion: These results indicated that the present NP should promote the efficacy of QE, and might have useful therapeutic potential in the treatment of solid tumors.

Reliability of a Single β-Thromboglobulin Measurement in a Diabetic Population : Importance of PGE1 in Anticoagulant Mixture

1987 ◽  
Vol 57 (02) ◽  
pp. 201-204 ◽  
Author(s):  
P Y Scarabin ◽  
L Strain ◽  
C A Ludlam ◽  
J Jones ◽  
E M Kohner
Keyword(s):  
In Vitro Release ◽  
Mean Value ◽  
Reliable Estimate ◽  
Diabetic Patients ◽  
Single Measurement ◽  
Diabetic Population ◽  
The Difference ◽  
Vitro Release

SummaryDuring the collection of samples for plasma β-thromboglobulin (β-TG) determination, it is well established that artificially high values can be observed due to in-vitro release. To estimate the reliability of a single β-TG measurement, blood samples were collected simultaneously from both arms on two separate occasions in 56 diabetic patients selected for a clinical trial. From each arm, blood was taken into two tubes containing an anticoagulant mixture with (tube A) and without (tube B) PGE!. The overall mean value of B-TG in tube B was 1.14 times higher than in tube A (p <0.01). The markedly large between-arms variation accounted for the most part of within-subject variation in both tubes and was significantly greater in tube B than in tube A. Based on the difference between B-TG values from both arms, the number of subjects with artifically high B-TG values was significantly higher in tube B than in tube A on each occasion (overall rate: 28% and 14% respectively). Estimate of between-occasions variation showed that B-TG levels were relatively stable for each subject between two occasions in each tube. It is concluded that the use of PGEi decreases falsely high B-TG levels, but a single measurement of B-TG does not provide a reliable estimate of the true B-TG value in vivo.

Development, in vitro and in vivo Evaluations of Solid-Lipid Microparticles based on Solidified Micellar Carrier System for Oral Delivery of Cefepime

2017 ◽  
Vol 10 (1) ◽  
pp. 3582-3593
Author(s):  
Chukwuebuka Umeyor ◽  
Uchechukwu Nnadozie ◽  
Anthony Attama
Keyword(s):  
Oral Delivery ◽  
In Vitro Release ◽  
Carrier System ◽  
Solid Lipid ◽  
Solid Lipid Microparticles ◽  
Release Study ◽  
Lipid Microparticles ◽  
Vitro Release

This study seeks to formulate and evaluate a solid lipid nanoparticle-based, solidified micellar carrier system for oral delivery of cefepime. Cefepime has enjoyed a lot of therapeutic usage in the treatment of susceptible bacterial infections; however, its use is limited due to its administration as an injection only with poor patient compliance. Since oral drug administration encourage high patient compliance with resultant effect in improved therapy, cefepime was formulated as solid lipid microparticles for oral delivery using the concept of solidified micellar carrier system. The carrier system was evaluated based on particle yield, particle size and morphology, encapsulation efficiency (EE %), and thermal analysis using differential scanning calorimeter (DSC). Preliminary microbiological studies were done using gram positive and negative bacteria. In vitro release study was performed using biorelevant media, while in vivo release study was performed in white albino rats. The yield of solid lipid microparticles (SLM) ranged from 84.2 – 98.0 %. The SLM were spherical with size ranges of 3.8 ± 1.2 to 42.0 ± 1.4 µm. The EE % calculated ranged from 83.6 – 94.8 %. Thermal analysis showed that SLM was less crystalline with high potential for drug entrapment. Microbial studies showed that cefepime retained its broad spectrum anti-bacterial activity. In vitro release showed sustained release of cefepime from SLM, and in vivo release study showed high concentration of cefepime released in the plasma of study rats. The study showed that smart engineering of solidified micellar carrier system could be used to improve oral delivery of cefepime.

Formulation and Evaluation of Itopride Hydrochloride Floating Beads for Gastroretentive Delivery

2013 ◽  
Vol 6 (4) ◽  
pp. 2269-2280
Author(s):  
Nagratna Dhople ◽  
P N Dandag ◽  
A P Gadad ◽  
C K Pandey ◽  
Masthiholimath V S
Keyword(s):  
Sustained Release ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Sustained Release Formulation ◽  
Prokinetic Drug ◽  
Drug Entrapment Efficiency ◽  
Itopride Hydrochloride ◽  
Vitro Release

A gastroretentive sustained release system of itopride hydrochloride was formulated to increase the gastric residence time and modulate its release behavior. Itopride hydrochloride is a prokinetic drug used in the treatment of gastroeosophageal reflux disease, Non-ulcer dyspepsia and as an antiemetic. Hence, itopride hydrochloride beads were prepared by emulsion gelation method by employing low methoxy pectin and sodium alginate as sustained release polymers in three different ratios alone and in combination and sunflower oil was used to enable floating property to the beads. The effect of variation in polymer and their concentration was investigated. The beads were evaluated for production yield, particle size, swelling index, density measurement, buoyancy, drug content, drug entrapment efficiency, in vitro release characteristics and release kinetic study. Based on drug entrapment efficiency, buoyancy, swelling and in vitro release, F9 was selected as the optimized formulation. F9 was further subjected to surface morphology by SEM, in vitro release comparison with marketed formulation, in vivo floating study in rabbits and stability study for 90 days. In vitro release follows zero order and fitted in Korsmeyer peppas model (Non-Fickian release). Therefore, the rate of drug release is due to the combined effect of drug diffusion and polymer swelling. The in vivo X-ray studies revealed that the beads were floating in the rabbit stomach up to 10 hours. Thus, it was concluded that the sustained release formulation containing itopride hydrochloride was found to improve patient compliance, minimize the side effects and decrease the frequency of administration.

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