Sustained-release Delivery System Research Articles

Electrospun nanofibers using β-cyclodextrin grafted chitosan macromolecules loaded with indomethacin as an innovative drug delivery system

Electrospun nanofibers, as an innovative drug delivery system, provide selective, effective, and safe drug release. The present study aimed to fabricate nanofibers based on β-cyclodextrin grafted chitosan (β-CD-g-CS) macromolecules with incorporated drug via the blend electrospinning technique. The grafting of β-CD onto chitosan (CS) was confirmed by FT-IR, 1H NMR, TGA, XRD, and EDX analysis. Indomethacin was encapsulated in the β-CD-g-CS matrix as blend nanofibers using electrospinning in presence of polyvinyl alcohol (PVA). The SEM images revealed nanofibers with diameters at the nanoscale. The unique features of β-CD-g-CS/PVA as drug delivery system were investigated using indomethacin as a model drug molecule. Controlled release of indomethacin from nanofibers was studied in PBS solution by measuring the absorbance by UV–Vis spectrophotometer. The drug release profile exhibited that the rate of drug release can be tailored by polymer type and changing the drug/polymer ratio. The physicomechanical properties of the developed nanofibers were analyzed by tensile strength and water contact angle. The results demonstrated that β-CD-g-CS revealed enhanced wettability as well as favorable physicomechanical properties. In addition, the growth rate of the L929 cells on the CS and β-CD-g-CS nanofibers was not significantly inhibited and even improved cell proliferation. These findings indicated that β-CD-g-CS nanofibers could be appropriate as a smart drug delivery system for sustained release of indomethacin as an anti-inflammatory medicine in the wound healing and tissue engineering approaches in orthopedic applications.

4-Iodo-6-phenylpyrimidine (4-IPP) suppresses fibroblast-like synoviocyte- mediated inflammation and joint destruction associated with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic immune-mediated inflammatory disease that significantly impacts patients' quality of life. Fibroblast-like synovial cells (FLSs) within the synovial intima exhibit "tumor-like" properties such as increased proliferation, migration, and invasion. Activation of FLSs and secretion of pro-inflammation factors result in pannus formation and cartilage destruction. As an inhibitor of the cytokine, macrophage migration inhibitory factor (MIF), 4-Iodo-6-phenylpyrimidine (4-IPP) has been shown to reduce cell proliferation, migration, invasion, and the secretion of pro-inflammatory mediators in a variety of diseases. However, the usefulness of 4-IPP for RA treatment has not been assessed and was the purpose of this study. In vitro, 4-IPP was demonstrated to inhibit proliferation, migration, and invasion of RA FLSs, as well as the expression of pro-inflammatory cytokines. 4-IPP was also shown to inhibit MIF-induced phosphorylation of ERK, JNK, and p38, as well as reduce expression of COX2 and PGE2. In order to efficiently deliver 4-IPP to anatomical RA sites, we developed lactic-co-glycolic acid (PLGA) nanospheres, which not only protected 4-IPP from degradation but also controlled the release of 4-IPP. 4-IPP/PLGA nanospheres had potent anti-inflammatory activity and a high degree of biosafety. Results showed that local 4-IPP concentration was increased by nanosphere delivery, effectively reducing the inflammatory microenvironment as well as synovial inflammation, joint swelling, and cartilage destruction in a collagen-induced rheumatoid arthritis (CIA) rat model. Therefore, 4-IPP nanospheres are a sustained-release delivery system that may be an effective therapeutic strategy for RA treatment.

Thermosensitive Biodegradable Hydrogels for Local and Controlled Cerebral Delivery of Proteins: MRI-Based Monitoring of In Vitro and In Vivo Protein Release.

Hydrogels have been suggested as novel drug delivery systems for sustained release of therapeutic proteins in various neurological disorders. The main advantage these systems offer is the controlled, prolonged exposure to a therapeutically effective dose of the released drug after a single intracerebral injection. Characterization of controlled release of therapeutics from a hydrogel is generally performed in vitro, as current methods do not allow for in vivo measurements of spatiotemporal distribution and release kinetics of a loaded protein. Importantly, the in vivo environment introduces many additional variables and factors that cannot be effectively simulated under in vitro conditions. To address this, in the present contribution, we developed a noninvasive in vivo magnetic resonance imaging (MRI) method to monitor local protein release from two injected hydrogels of the same chemical composition but different initial water contents. We designed a biodegradable hydrogel formulation composed of low and high concentration thermosensitive polymer and thiolated hyaluronic acid, which is liquid at room temperature and forms a gel due to a combination of physical and chemical cross-linking upon injection at 37 °C. The in vivo protein release kinetics from these gels were assessed by MRI analysis utilizing a model protein labeled with an MR contrast agent, i.e. gadolinium-labeled albumin (74 kDa). As proof of principle, the release kinetics of the hydrogels were first measured with MRI in vitro. Subsequently, the protein loaded hydrogels were administered in male Wistar rat brains and the release in vivo was monitored for 21 days. In vitro, the thermosensitive hydrogels with an initial water content of 81 and 66% released 64 ± 3% and 43 ± 3% of the protein loading, respectively, during the first 6 days at 37 °C. These differences were even more profound in vivo, where the thermosensitive hydrogels released 83 ± 16% and 57 ± 15% of the protein load, respectively, 1 week postinjection. Measurement of volume changes of the gels over time showed that the thermosensitive gel with the higher polymer concentration increased more than 4-fold in size in vivo after 3 weeks, which was substantially different from the in vitro behavior where a volume change of 35% was observed. Our study demonstrates the potential of MRI to noninvasively monitor in vivo intracerebral protein release from a locally administered in situ forming hydrogel, which could aid in the development and optimization of such drug delivery systems for brain disorders.

Sirolimus-exuding core-shell nanofibers as an implantable carrier for breast cancer therapy: preparation, characterization, in vitro cell studies, and in vivo anti-tumor activity

Objective Breast cancer accounts for significant mortality worldwide. Here, we develop a localized, sustained-release delivery system for breast cancer therapy. Methods Sirolimus (SIR) core-shell nanofibers (NFs) are fabricated by coaxial electrospinning with poly(ε-caprolactone) (PCL) for the core and chitosan and PCL for the shell. The NFs were characterized by SEM, AFM, TEM, XRD, FTIR, water uptake, water contact angle, mechanical properties, drug content, and in vitro release. In vitro and in vivo anticancer effects were investigated. Results A sustained release behavior is observed during 480 h that is more extended compared to monoaxial NFs. In vitro cytotoxicity and Annexin V/propidium iodide assays indicate that SIR-loaded coaxial NFs are effective in inhibiting proliferation of 4T1 and MCF-7 cells. Implantation of SIR NFs in 4T1 breast tumor-bearing mice inhibits tumor growth significantly compared to free drug. Histopathological examination shows that suppression of tumor growth by SIR NFs is associated with apoptotic cell death. Furthermore, anti-cancer effects are also confirmed by decreased expression levels of Ki-67, MMP-2, and MMP-9. Histological observation of organs, serological analyses, and the lack of body weight changes indicate in vivo safety of SIR NFs. Conclusions Altogether, we show here that incorporation of SIR into core-shell NFs could act as an effective drug release depot and induce a sustained antitumor response.

Design and development of carboxymethylcellulose ester of curcumin as sustained release delivery system in liver

In the present work chemical transformation of carboxymethylcellulose with curcumin in ester form has led to the development of target specific sustained release delivery system for curcumin in presence of liver esterases. We here report synthesis, characterizations (FTIR, SEM and XRD) curcumin-carboxymethylcellulose ester (Cur-CMC ester) and its target specific hydrolysis to release curcumin. Cur-CMC ester has been found stable when simulated in-vitro in gastric fluid (pH 1.2) and in intestinal fluid (pH 6.8). On in-vitro simulation in liver homogenate curcumin is released from Cur-CMC ester after hydrolysis in a consistent amount (∼43 %) for 5 h. The release of curcumin from ester was highest at pH 8.0 in presence of liver enzymes. The present study suggested that modified CMC support can not only be used for the delivery of curcumin in liver but also acts as prodrug system and released free curcumin in presence of liver esterases.

Pharmacokinetic Evaluation of Thermosensitive Sustained Release Formulations Developed for Subcutaneous Delivery of Protein Therapeutics

Injectable, thermosensitive hydrogels, constructed from cross-linked polymers, can offset the limitations of other sustained release delivery systems, overcome constrains of available therapies, and improve patient compliance to chronic therapy. The goal of this project was to identify and evaluate such sustained release, in situ formulations that can help achieve prolonged exposure of protein therapeutics with a short systemic half-life. Natural polymers were used to develop injectable, thermosensitive in situ hydrogels and single-chain variable fragment (scFv) of trastuzumab was used as the model protein with a short half-life. The three polymer combinations tested were: (1) Chitosan and β-glycerophosphate, (2) Chitosan, β-glycerophosphate, and Hyaluronic Acid, and (3) Hyaluronic Acid and Dextran. In vitro drug release experiments were conducted, using different combinations of various polymer concentrations and different drug loading amounts, to identify optimal combinations with prolonged and controlled drug release while exhibiting minimal burst release effect. Select formulations were injected subcutaneously in normal mice to evaluate the pharmacokinetics of scFv for 14 days and identify drug release kinetics in vivo. A two-compartment PK model was also established to quantitatively characterize the release kinetics and disposition of scFv following in vivo administration of the hydrogels. The scFv was undetectable in plasma after 4 and 24 hours following intravenous and subcutaneous administration, respectively. However, all three hydrogel systems were found to provide controlled release of scFv in vivo and maintain detectable concentrations of scFv for at least 14 days. The results suggested that subcutaneous injection of thermosensitive in situ hydrogels may be used to achieve sustained exposure of protein therapeutics which have a very short half-life and thus require frequent administration.

Modeling of the effect of cerebrospinal fluid flow modulation on locally delivered drugs in the brain.

Cerebrospinal fluid (CSF) plays a vital role in maintaining brain homeostasis and recent research has focused on elucidating the role that convective flow of CSF plays in brain health. This paper describes a computational compartmental model of how CSF dynamics affect drug pharmacokinetics in the rat brain. Our model implements a local, sustained release approach for drug delivery to the brain. Simulation outputs highlight the potential for modulating CSF flow to improve overall drug pharmacokinetics in the central nervous system and suggest that concomitant CSF modulation and optimized drug release rates from implantable depots can be used to engineer the duration of action of chemotherapeutics. As an example, the tissue exposure of temozolomide, the standard of care treatment for glioblastoma, was modeled in conjunction with two CSF-modulating drugs: acetazolamide and verapamil. Simulations indicate that temozolomide exposure in the interstitial fluid is increased by 25% when using local sustained release delivery systems and concomitant acetazolamide delivery to reduce CSF production. This computational model can be used to produce insight on how to appropriately modulate CSF production and engineer drug release to tailor drug exposure in the brain while limiting off-target effects. As new research continues to elucidate the dynamic roles of CSF, this model can be further improved and leveraged to provide information on how CSF modulation may play a beneficial role in treating a wide variety of neurological disease.

Synthesis, Characterization, Isoconversional Analysis and Degradation Kinetics of Novel Acetate Coated Hydroxyethyl Starch: A New Candidate as a Drug Carrier

The hydroxethyl starch (HES) is very trending biopolymer in biomedical field. In recent research we have successfully synthesized a novel ester of HES, i.e., HES-acetate by acetylation of HES followed by investigation of its thermal behavior. The successful acetylation of HES was confirmed by Fourier Transform Infrared (FTIR) and Proton-Nuclear Magnetic Resonance (1H NMR) spectroscopic techniques. Thermal stability and thermal degradation kinetics of HES-acetate were investigated by thermo-gravimetric analysis. Flynn–Waal–Ozawa model was fitted to the thermal data to find the values of thermodynamic triplet (ΔS, ΔG and ΔE). Energy of activation (Ea) values of the major thermal degradation steps were found to be 242.85 and 287.17 kJ mol–1 for HES and HES-acetate, respectively. The order of degradation, integral procedural decomposition temperature (IPDT) and index of intrinsic thermal stability (ITS) were also taken into account. The results of the thermal analysis reveal that the HES-acetate gained significant thermal stability as compared to that of HES. This benign polysaccharide-based material was investigated for its potential in drug release studies by taking caffeine as a model drug. HES-acetate-based matrix tablets showed sustained release behavior of the drug indicating its potential for the development of oral delivery systems for sustained drug release.

Potential Combinatory Effect of Cannabidiol and Triclosan Incorporated into Sustained Release Delivery System against Oral Candidiasis.

Candida albicans is a common fungal pathogen. Biofilm formation on various surfaces is an important determinant of C. albicans pathogenicity. Our previous results demonstrated the high potential of cannabidiol (CBD) to affect C. albicans biofilms. Based on these data, we investigated the possibility of incorporating CBD and/or triclosan (an antimicrobial agent that is widely utilized in dentistry) in a sustained-release varnish (SRV) (SRV-CBD, SRV-triclosan) to increase their pharmaceutical potential against C. albicans biofilm, as well as that of the mixture of the agents into SRV (SRV-CBD/triclosan). The study was conducted in a plastic model, on agar, and in an ex vivo tooth model. Our results demonstrated strong antibiofilm activity of SRV-CBD and SRV-triclosan against C. albicans in all tested models. Both formulations were able to inhibit biofilm formation and to remove mature fungal biofilm. In addition, SRV-CBD and SRV-triclosan altered C. albicans morphology. Finally, we observed a dramatic enhancement of antibiofilm activity when combined SRV-CBD/triclosan was applied. In conclusion, we propose that incorporation of CBD or triclosan into SRV is an effective strategy to fight fungal biofilms. Importantly, the data demonstrate that our CBD/triclosan varnish is safe, and is not cytotoxic for normal mammalian cells. Furthermore, we propose that CBD and triclosan being in mixture in SRV exhibit complementary antibiofilm activity, and thus can be explored for further development as a potential treatment against fungal infections.

Polyhydroxyalkanoate Decelerates the Release of Paclitaxel from Poly(lactic-co-glycolic acid) Nanoparticles.

Biodegradable nanoparticles (NPs) are preferred as drug carriers because of their effectiveness in encapsulating drugs, ability to control drug release, and low cytotoxicity. Although poly(lactide co-glycolide) (PLGA)-based NPs have been used for controlled release strategies, they have some disadvantages. This study describes an approach using biodegradable polyhydroxyalkanoate (PHA) to overcome these challenges. By varying the amount of PHA, NPs were successfully fabricated by a solvent evaporation method. The size range of the NPS ranged from 137.60 to 186.93 nm, and showed zero-order release kinetics of paclitaxel (PTX) for 7 h, and more sustained release profiles compared with NPs composed of PLGA alone. Increasing the amount of PHA improved the PTX loading efficiency of NPs. Overall, these findings suggest that PHA can be used for designing polymeric nanocarriers, which offer a potential strategy for the development of improved drug delivery systems for sustained and controlled release.

Silk Fibroin Hydrogel Reinforced With Magnetic Nanoparticles as an Intelligent Drug Delivery System for Sustained Drug Release.

Due to the well-known biocompatibility, tunable biodegradability, and mechanical properties, silk fibroin hydrogel is an exciting material for localized drug delivery systems to decrease the therapy cost, decrease the negative side effects, and increase the efficiency of chemotherapy. However, the lack of remote stimuli response and active drug release behavior has yet to be analyzed comparatively. In this study, we developed magnetic silk fibroin (SF) hydrogel samples through the facile blending method, loaded with doxorubicin hydrochloride (DOX) and incorporated with different concentrations of iron oxide nanoparticles (IONPs), to investigate the presumable ability of controlled and sustained drug release under the various external magnetic field (EMF). The morphology and rheological properties of SF hydrogel and magnetic SF hydrogel were compared through FESEM images and rheometer analysis. Here, we demonstrated that adding magnetic nanoparticles (MNPs) into SFH decreased the complex viscosity and provided a denser porosity with a bigger pore size matrix structure, which allowed the drug to be released faster in the absence of an EMF. Release kinetic studies show that magnetic SF hydrogel could achieve controlled release of DOX in the presence of an EMF. Furthermore, the drug release from magnetic SF hydrogel decreased in the presence of a static magnetic field (SMF) and an alternating magnetic field (AMF), and the release rate decreased even more with the higher MNPs concentration and magnetic field strength. Subsequently, Wilms' tumor and human fibroblast cells were cultured with almost the same concentration of DOX released in different periods, and cell viability was investigated using MTT assay. MTT results indicated that the Wilms' tumor cells were more resistant to DOX than the human fibroblasts, and the IC50 values were calculated at 1.82 0.001 and 2.73 0.004 (μg/ml) for human fibroblasts and Wilms' tumor cells, respectively. Wilms' tumor cells showed drug resistance in a higher DOX concentration, indicating the importance of controlled drug delivery. These findings suggest that the developed magnetic SFH loaded with DOX holds excellent potential for intelligent drug delivery systems with noninvasive injection and remotely controlled abilities.

Towards innervation of bioengineered muscle constructs: Development of a sustained neurotrophic factor delivery and release system

Surgical implantation of biomanufactured skeletal muscle constructs has recently emerged as a promising strategy to treat volumetric muscle defects. However, due to the slow rate of neural regeneration and integration, timely innervation of the implanted constructs with the host peripheral nerves remains an unresolved challenge. This study aims to develop a sustained release neurotrophic factor (NF) delivery system to accelerate peripheral nerve regeneration and innervation of three-dimensional (3D) bioprinted skeletal muscle constructs. Poly (lactic-co-glycolic acid) (PLGA) microspheres were selected as a delivery system for efficient loading and sustained release of two potent NFs: ciliary neurotrophic factor (CNTF) and glial cell line-derived neurotrophic factor (GDNF). We demonstrate that the NFs can be loaded within the PLGA microspheres with a high encapsulation efficiency (75.4% ± 12.6%). The NF-loaded microspheres were incorporated into the fibrinogen-based bioink used to produce biomanufactured skeletal muscle constructs and tested for printability. The microspheres did not change the viscoelastic properties of the bioink, nor did they affect the viability of human muscle progenitor cells. The release kinetic test confirmed that the bioprinted muscle constructs with the NFs-loaded microspheres released the NFs in a sustained manner compared to the bioprinted muscle construct without microspheres. The released NFs maintained their biological activities. In an in vitro neurite outgrowth assay, the NFs released from the PLGA microspheres facilitated the neurite growth over a longer time scale than the NFs directly loaded in the hydrogel. These results demonstrate the feasibility of incorporating the microsphere-based NF delivery system for accelerating neural regeneration in future in vivo applications involving biomanufactured muscle constructs.

Preparation of layered beta-cypermethrin-carrying microcapsules from Pickering emulsion of hollow mesoporous silica nanoparticles

Microcapsules may be viable carriers in sustained-release delivery system for pesticides due to their attractive core structures and diverse wall materials. However, previous research on microcapsules loaded with fat-soluble pesticides was mainly concentrated on the single shell and core structure. In our study, benefiting from the stabilization mechanism of solid particles in Pickering emulsions, hollow mesoporous silica nanoparticles (HMSNs) were fully utilized to serve as pesticides-carrying carriers and enrich the structure of microcapsules. An oil-in-water (O/W) Pickering emulsion composed of a dichloromethane/water system was obtained at a concentration of HMSNs above 0.2% (w/v). An O/W emulsion with better stability was formed by adding gelatin aqueous dispersion (1 wt%) for co-emulsification. A novel layered beta-cypermethrin-carrying microcapsule was successfully prepared, in which HMSNs pre-loaded with a small amount of beta-cypermethrin were covered the shell surface of the microcapsules. Furthermore, the as-prepared microcapsules have good sustained-release performance, and the release behavior of beta-cypermethrin could be explained by first-order kinetic model and Korsmeyer-Peppas model. Bioassay results indicated that the content of microcapsules reached at 5 wt%, the prepared film has a better mosquito repellent effect. Hence, this study provided a simple preparation of functionalized layered sustained-release microcapsules carrying fat-soluble pesticides, and the prepared microcapsules could be used as the anti-mosquito coating additives.

Hemoglobin bio-adhesive nanoparticles as a colon-specific delivery system for sustained release of 5-aminosalicylic acid in the effective treatment of inflammatory bowel disease

A colonic drug delivery system was developed to specifically deliver 5-aminosalicylic acid (5-ASA) to the inflamed site by conjugating with hemoglobin nanoparticles (HbNPs). The 5-ASA-HbNPs (eight 5-ASA molecules per Hb molecule) with the size of 220 nm and zeta potential of −14.6 mV is a tailored nanoparticle able to pass through the mucus layer. The 5-ASA-HbNPs do not undergo chemical and enzymatic hydrolysis in the simulated gastrointestinal fluids over 6 h. Significantly higher cellular uptakes and prolonged release was seen for the 5-ASA-HbNPs in Caco-2 cells, compared to free 5-ASA over 72 h. In addition, 5-ASA-HbNPs revealed similar therapeutic effectiveness with free 5-ASA against tumor necrosis factor and showed less inhibitory concentration (IC50) for myeloperoxidase enzyme activity. In vivo imaging of mouse demonstrated the localization of drug in the descending colon after oral administration and about 15% of the administered dose was recovered as 5-ASA from urine in 6 h. The use of these nanoparticles with the mucus adhesion properties and permeability to intestinal epithelial cells can be a good candidate with potential application in the colonic drug delivery field.

Tramadol extended-release porous silicon microcarriers: A kinetic, physicochemical and biological evaluation

Thermally oxidized porous silicon particles have been widely studied as drug delivery systems for sustained release. In this work, TOPSip with different particle and pore dimensions were synthesized by electrochemical etching and used as microcarriers to sustain tramadol hydrochloride, a centrally acting opiate analgesic. The physicochemical and morphological properties of nanostructured TOPSip were fully characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectrometry and zeta potential. Modulation of the etching parameters allowed the control of the nano-pore size from 6 nm to 33 nm and particle size from 0.8 to 31 μm. Furthermore, TR loading capacity in TOPSip-OH was quantified by UV–Vis spectroscopy. TOPSip-OH with the smallest pore size exhibited a TR loading capacity of 10%. In contrast, TOPSip-OH with the highest pore dimensions showed an increase in the loading capacity of tramadol up to 31%. TR release was carefully studied in simulated gastric (pH 1.2) and intestinal fluids (pH 6.8). The released profiles demonstrated that microparticles with ∼6 nm pore size exhibited a sustained release up to 24 h with burst effect depending on pH. Release profiles of composites were compared with those obtained from a commercial extended-release tramadol formulation in both pH. It was observed that commercial composite released TR entirely after 1 h. TR cumulative release data were fitted using different mathematical models. Korsmeyer-Peppas fitted well for both simulated fluids. Through in vivo assessment, it was demonstrated that TR-loaded TOPSip sustains antinociceptive and anti-inflammatory effects compared to administration of tramadol at the same dose, which is a novel contribution of this work.

Spawning Performance and Sex Steroid Levels in Female Pikeperch Sander lucioperca Treated with Poly(lactic-co-glycolic acid) Microparticles.

Simple SummaryPikeperch Sander lucioperca is a promising candidate for intensive aquaculture. However, controlled reproduction has become the major bottleneck in pikeperch production. To improve and optimize its artificial reproduction, an effective method for hormone treatment is needed. The use of a poly(lactic-co-glycolic acid) microparticle-sustained-release system to administer gonadotropin-releasing hormone agonist to pikeperch resulted in acceptable reproductive output. Our results establish the potential of poly(lactic-co-glycolic acid) microparticle as a novel tool for hormone treatment in fish.Pikeperch Sander lucioperca is a piscivorous species considered a promising candidate for the diversification of intensive aquaculture. This study aimed to determine the effect of a sustained-release delivery system incorporating mammalian gonadotropin-releasing hormone agonist (mGnRHa) into poly(lactic-co-glycolic acid) (PLGA) microparticles on the sex steroid levels and aspects of artificial reproduction of pikeperch. Fish were divided into four groups and injected with 20 µg mGnRHa/kg, 5-day release microparticles encapsulated with 5 µg GnRHa/kg BW (PLGA 5), 20 µg GnRHa/kg (PLGA 20), or 1 mL/kg 0.9% NaCl (control). Cumulative percentage ovulation was 100% in the PLGA 5 group, significantly higher than in other tested groups. No differences among groups were observed in latency or fecundity. The level of 11-ketotestosterone (11-KT) peaked at 40 h post-injection, and was sustained during ovulation, in all treated groups. The 17β-estradiol (E2) concentration increased in the mGnRHa-only group immediately after hormone injection, while both PLGA groups showed a reduction in E2 after injection, continuing to decrease until ovulation. A low dose of mGnRHa in PLGA microparticles significantly improves induction of ovulation and results in acceptable reproductive performance, which may positively affect pikeperch production under controlled conditions.

Preparation and evaluation of ibuprofen loaded sodium alginate/sodium cmc mucoadhesive drug delivery system for sustained release

Preparation and evaluation of ibuprofen loaded sodium alginate/sodium cmc mucoadhesive drug delivery system for sustained release

Sustained Release of Risedronate from PLGA Microparticles Embedded in Alginate Hydrogel for Treatment of Bony Lesions

Background:Inflammatory bone resorption in periodontitis can lead to tooth loss. Systemic administration of bisphosphonates such as risedronate for preventing bone resorption can cause adverse effects. ALG and PLGA microparticles have been studied as drug delivery systems for sustained release of drugs. Therefore, the release pattern of risedronate from PLGA microparticles embedded with ALG was studied as a drug delivery system for sustained release of the drug, which can be used in local administrations. Methods:Risedronate-containing PLGA microparticles were fabricated using double emulsion solvent evaporation technique. Ionic cross-linking method was used to fabricate risedronate-loaded ALG. Risedronate-containing PLGA microparticles were then coated with ALG. The calibration curve of risedronate was traced to measure EE and study the release pattern. SEM imaging was carried out, and cell toxicity was examined using MTT assay. Statistical analysis of data was carried out using SPSS ver. 20 software, via one-way ANOVA and Tukey’s tests. Results:SEM imaging showed open porosities on ALGs. The mean EE of PLGA microparticles for risedronate was 57.14 ± 3.70%. Risedronate released completely after 72 h from ALG, and the cumulative release was significantly higher (p = 0.000) compared to PLGA microspheres coated with ALG, which demonstrated sustained released of risedronate until day 28. Risedronate-loaded ALG showed a significant decrease in gingival fibroblasts cell viability (p < 0.05). Conclusion: Alginate-coated PLGA microspheres could release risedronate in a sustained and controlled way and also did not show cell toxicity. Therefore, they seem to be an appropriate system for risedronate delivery in local applications.

Floating Microsphere of Curcumin as Targeted Gastro-retentive Drug Delivery System

Microspheres carrier system made from natural or synthetic polymers used in sustained release drug delivery system. The present study involves formulation and evaluation of floating microspheres of Curcumin for improving the drug bioavailability by prolongation gastric residence time. Curcumin, natural hypoglycemic agent is a lipophilic drug, absorbed poorly from the stomach, quickly eliminated and having short half-life so suitable to formulate floating drug delivery system for sustained release. Floating microspheres of curcumin were formulated by solvent evaporation technique using ethanol and dichloromethane (1:1) as organic solvent and incorporating various synthetic polymers as coating polymer, sustain release polymers and floating agent. The final formulation were evaluated various parameters such as compatibility studies, micrometric properties, In-vitro drug release and % buoyancy. FTIR studies showed that there were no interaction between drug and excipients. The surface morphology studies by SEM confirmed their spherical and smooth surface. The mean particles size were found to be 416-618µm, practical yield of microspheres was in the range of 60.21±0.052% - 80.87±0.043%, drug entrapment efficiency 47.4±0.065% - 77.9±0.036% and % buoyancy 62,24±0.161% - 88.63±0.413%. Result show that entraptmency increased as polymer (Eudragit RS100) conc. Increased. The drug release after 12 hrs. was 72.13% - 87.13% and it decrease as a polymer (HPMC, EC) concentration was decrease.

Prevention of abdominal adhesion by apolycaprolactone/phospholipid hybrid film containing quercetin and silver nanoparticles.

Aim: To develop quercetin-loaded poly(caprolactone) (PCL)/soybean phosphatidylcholine (PC) films coated with silver (Ag) to prevent the formation of postoperative adhesions (POA). Materials & methods: Films were prepared using thesolvent casting method, coated with Ag, and underwentin vitro tests. In vivo studies were conductedemploying an animal model of sidewall defect and cecum abrasion. Results: Films showed sustained release behavior of quercetin and Ag. Coating films with Ag improved their antimicrobial activity. In vivo studies confirmed superior antiadhesion properties of films compared with thecontrol groups evaluated by gross observation, histochemical stainingand immunohistochemistry analyses. Conclusion: Ag-Q-PCL-PC films are a potential candidate topreventPOA by acting as a sustained release delivery system andphysical barrier.