Drug Release In pH Research Articles

Improvement of Bioavailability of Sildenafil Citrate Through Taste Masked Orodispersible Film for Pulmonary Hypertension Management.

The oral bioavailability of sildenafil citrate is approximately 43%, primarily limited by the low aqueous solubility and first-pass effect. Considering the drug properties and biopharmaceutical considerations, this study aimed to develop an immediate release, taste masked orodispersible film (ODF) of sildenafil citrate for the efficient management of pulmonary arterial hypertension (PAH). The optimization was done by applying 32 full-factorial design. The drug-loaded film was prepared and evaluated for the physical and mechanical parameters like; thickness, disintegration time, tensile strength, elongation, swelling index, content uniformity, disintegration and in vitro drug release in pH 6.2 stimulated salivary fluid. The FTIR and DSC data proved excellent compatibility between the drug and polymers used. The time taken for disintegration by the optimized film was about 62.66s, while the drug release was observed ~ 96% in 10min. Pharmacokinetic studies exhibited better sildenafil plasma level (p < 0.05) and Cmax (p < 0.001) of orally disintegrating film which is significantly higher than the oral drug solution. The AUC0-8 (24874.425 ± 1234.45ng. h/mL) in the oromucosal application was 1.2-fold more (p < 0.0001) than the control. The presence of sweetening and flavoring agents in the formulation masked the drug bitterness, resulting in a higher intake of the formulation in rats compared to the unmasked drug solution, as observed with in vivo taste masking studies. The importance of ODF as a feasible, effective, and optimal approach for delivering sildenafil citrate via oromucosal administration for the treatment of PAH was successfully highlighted by these results.

Fabrication of Quercetin-Functionalized Morpholine and Pyridine Motifs-Laden Silk Fibroin Nanofibers for Effective Wound Healing in Preclinical Study.

Choosing suitable wound dressings is crucial for effective wound healing. Spun scaffolds with bioactive molecule functionalization are gaining attention as a promising approach to expedite tissue repair and regeneration. Here, we present the synthesis of novel multifunctional quercetin with morpholine and pyridine functional motifs (QFM) embedded in silk fibroin (SF)-spun fibers (SF-QFM) for preclinical skin repair therapies. The verification of the novel QFM structural arrangement was characterized using ATR-FTIR, NMR, and ESI-MS spectroscopy analysis. Extensive characterization of the spun SF-QFM fibrous mats revealed their excellent antibacterial and antioxidant properties, biocompatibility, biodegradability, and remarkable mechanical and controlled drug release capabilities. SF-QFM mats were studied for drug release in pH 7.4 PBS over 72 h. The QFM-controlled release is mainly driven by diffusion and follows Fickian's law. Significant QFM release (40%) occurred within the first 6 h, with a total release of 79% at the end of 72 h, which is considered beneficial in effectively reducing bacterial load and helping expedite the healing process. Interestingly, the SF-QFM-spun mat demonstrated significantly improved NIH 3T3 cell proliferation and migration compared to the pure SF mat, as evidenced by the complete migration of NIH 3T3 cells within 24 h in the scratch assay. Furthermore, the in vivo outcome of SF-QFM was demonstrated by the regeneration of fresh fibroblasts and the realignment of collagen fibers deposition at 9 days post-operation in a preclinical rat full-thickness skin defect model. Our findings collectively indicate that the SF-QFM electrospun nanofiber scaffolds hold significant capability as a cost-effective and efficient bioactive spun architecture for use in wound healing applications.

Quality-by-design-engineered mitochondrial targeted nanoparticles for glioblastoma therapy.

Glioblastoma (GB, IDH-wildtype) constitutes the most aggressive primary malignant neoplasm with limited treatment modalities due to the blood-brain barrier (BBB) often restricting drug delivery. It also has an overall low survival rate with no curative solution, reinforcing the need for innovative formulation development for effective management of GB. This study explores a novel approach using triphenylphosphonium (TPP+)-conjugated chitosan nanoparticles for targeted mitochondrial delivery of temozolomide (TMZ) to GB cells. The conjugated nanoparticles were designed to leverage chitosan's biocompatibility and TPP's mitochondrial targeting ability. TMZ-loaded chitosan nanoparticles were systematically developed and optimized employing a Quality-by-Design (QbD) approach with a screening of factors (Taguchi design) followed by optimization (Box-Behnken design). The optimized nanoparticles had an average particle size of 138.1 ± 5 nm, PDI of 0.242 ± 0.04, and entrapment efficiency of 93.59 ± 3%. Further, a conjugate chitosan-TPP+ (CS-TPP+) was synthesized and validated, employing varied techniques such as NMR, FTIR, HPLC, zeta potential, and EDAX analysis. In vitro drug release in pH 5 phosphate buffer showed a sustained release for nanoparticulate formulations compared to the free drug solution further indicating that conjugation did not alter the release pattern of nanoparticles. With regards to intranasal delivery of the formulation, an ex vivo study carried out on goat nasal mucosa demonstrated greater retention of conjugated chitosan nanoparticles on nasal mucosa than free drug solution, and a mucin interaction study also corroborated this finding. In vitro cell line studies indicated nanoparticles' cytotoxic potential compared to TMZ solution. Overall, this study highlights the potential of TPP+-conjugated chitosan nanoparticles developed strategically for the targeted delivery of TMZ to mitochondria.

A new theranostic pH-responsive niosome formulation for doxorubicin delivery and bio-imaging against breast cancer

As one of the newest generations of nanoplatforms, smart nanotheranostics have attracted signifivant attentions for medical applications, especially in oncology and cancer treatment. Indeed, their capability to provide treatment and diagnosis simultaneously leads to reduce time and side effects along with improving the performance. This study aims to introduce a novel smart nano-platform composed of doxorubicin-loaded pH-responsive stealth niosomes containing CdSe/ZnS Quantum dots as an imaging agent. Drug loaded nano-platform was fabricated via thin-film hydration method and then evaluated using different physicochemical tests. The entrapment efficiency and release profile of doxorubicin were assessed at three different pH (4, 6.5, and 7.4). Biological features and imaging ability of the nanoparticles were also evaluated by MTT assay, apoptosis assay, and fluorescence microscopy. Results showed that the fabricated nanoparticles were round-shaped, with a mean size of about 100 ± 10 nm, −2 mV surface charge, and about 87% entrapment efficiency. The drug release profile presented a pH-responsive behavior (80, 60, and 40% drug release in pH 4, 6.5, and 7.4, respectively). The bio-activity assessments showed nearly 55% cytotoxicity effects via inducing cell apoptosis. Besides, the uptake of samples by the cells was confirmed through fluorescence imaging. Based on the results, this new nanoformulation could be considered as a candidate for future cancer theranostic applications.

Dispersion Performances and Fluorescent Behaviors of Naphthalic Anhydride Doped in Poly(acrylic acid) Frameworks for pH-Sensitive Ibuprofen Delivery via Fractal Evolution.

The pH-responsive fluorescent P(1,8-naphthalic anhydride (NA)-acrylic acid (AA)) matrix was successfully prepared by a doping method using poly(acrylic acid) (PAA) as a pH-sensitive polymer and NA as a fluorescent tracer. The fluorescent behaviors of the used NA dispersed in PAA frameworks were demonstrated based on fractal features combined with various characterizations, such as small-angle X-ray scattering (SAXS) patterns, photoluminescence (PL) spectra, scanning electron microscope (SEM) images, thermogravimetry (TG) profiles, Fourier transform infrared (FT-IR) spectroscopy, and time-resolved decays. The effects of NA-doping on the representative fluorescent P(NA-AA) were investigated, in which the fluorescent performance of the doped NA was emphasized. The results indicated that aggregated clusters of the doped NA were gradually serious with an increase in NA doping amount or extension of NA doping time, accompanied by an increase in mass fractal dimension (Dm) values. Meanwhile, the doped NA presented stable fluorescent properties during the swelling-shrinking process of PAA. Ibuprofen (IBU) was used as a model drug, and fractal evolutions of the obtained P(NA-AA) along with the drug loading and releasing behaviors were evaluated via SAXS patterns, in which the drug-loaded P(NA-AA) presented surface fractal (Ds) characteristics, while the Dm value varied from 2.94 to 2.58 during sustained drug-release in pH 2.0, indicating occurrences of its structural transformation from dense to loose with extension of IBU-releasing time. Finally, the cytotoxicity and cellular uptake behaviors of the obtained P(NA-AA) were preliminarily explored. These demonstrations revealed that the resultant P(NA-AA) should be a potential intelligent-responsive drug carrier for targeted delivery.

Central Composite Design for Optimization of Mitomycin C-Loaded Quantum Dots/Chitosan Nanoparticles as Drug Nanocarrier Vectors

Cancer is one of the most devastating diseases that leads to a high degree of mortality worldwide. Hence, extensive efforts have been devoted to the development of drug nanocarrier vectors as a potential new cancer treatment option. The main goal of this treatment is to deliver an anticancer medicine successfully and effectively to the patient's cells using non-toxic nanocarriers. Here, we present a drug delivery system to emphasize the optimization of an anticancer drug-loaded formulation using Mitomycin C (MMC) encapsulated in chitosan nanocarrier conjugated with a bioimaging fluorescence probe of Mn:ZnS quantum dots (MMC@CS-Mn:ZnS). Additionally, the Response Surface Methodology (RSM), which uses a quadratic model to forecast the behaviour of the nano-drug delivery system, was used to assess the optimization of encapsulation efficiency. In this investigation, the core points of the Central Composite Design (CCD) model were used with 20 runs and 6 replications. The encapsulation efficiency (EE%) was measured using UV-Vis spectroscopy at 362 nm. The highest EE% is 55.31 ± 3.09 under the optimum parameters of incubation time (105 min), concentration of MMC (0.875 mg/mL), and concentration of nanocarriers (5.0 mg/mL). Physicochemical characterizations for the nanocarriers were accessed using a nanosizer and field-emission scanning electron microscopy (FESEM). Three independent variables for the evaluation of the encapsulation efficiency were used, in which the incubation time, concentration of MMC, concentration of nanocarriers, and correlation for each variable were studied. Furthermore, the MMC drug release efficiency was carried out in four different solution pHs of 5.5, 6.0, 6.5, 7.0, and pH 7.5, and the highest cumulative drug release of 81.44% was obtained in a pH 5.5 release medium, followed by cumulative releases of 68.55%, 50.91%, 41.57%, and 32.45% in release mediums with pH 6.0, pH 6.5, pH 7.0, and pH 7.5. Subsequently, five distinct mathematical models-pseudo-first-order, pseudo-second-order, Hixson-Crowell, Korsmeyer-Peppas, and Higuchi kinetic models-were used to fit all of the drug release data. The Korsmeyers-Peppas model was found to fit it well, highlighting its importance for the log of cumulative drug release proportional to the log of time at the equilibrium state. The correlation coefficient value (R2) was obtained as 0.9527, 0.9735, 0.9670, 0.9754, and 0.9639 for the drug release in pH 5.5, pH 6.0, pH 6.5, pH 7.0, and pH 7.5, respectively. Overall, from the analysis, the as-synthesized MMC nanocarrier (MMC@CS-Mn:ZnS) synergistically elucidates the underlying efficient delivery of MMC and leverages the drug loading efficiency, and all these factors have the potential for the simultaneous curbing of non-muscle invasive bladder cancer reoccurrence and progression when applied to the real-time disease treatment.

In vitro cytotoxicity and anti-cancer drug release behavior of methionine-coated magnetite nanoparticles as carriers.

A novel and specific drug delivery for in vitro cancer targeted are developed successfully by a simple one-step method. A CoFe2O4@Methionine core-shell nanoparticle was prepared by the reflux assay which amino acid in the surface makes ferrite biocompatible, enhances its chemical stability, and improves the drug-loading capacity. The synthesized nanoparticles were characterized using FTIR, TGA, XRD, SEM, TEM, and VSM which coating amino acid on the surface of CoFe2O4 was confirmed by XRD and TGA. The appearance of a new peak for C≡N confirms the formation of Letrozole-loaded carrier in the FTIR. The vibrating sample magnetometer of both bare CoFe2O4 and Methionine-coated CoFe2O4 nanoparticles exhibited room-temperature superparamagnetic behavior with a saturation value of 46emu/g and 16.8emu/g, respectively. The morphology and size of samples were characterized by SEM and TEM that the average size of the particle was around 28-29nm. The loading of Letrozole and the effect of pH (5, 7.4) on the release behavior of the carrier was studied. The result of the drug release in pH is equal to 5 was about 88% which higher than pH is equal to 7.4. Also, the preparation had been evaluated for determining its cytotoxicity using MCF-7, MDA-MB-231, and MCF10A cells as an in vitro model, and the result vitro experiments showed that CoFe2O4@Methionine could significantly reduce cancer in cells model. These results demonstrate that core-shell nanoparticle was prepared is biocompatible and have potential use as drug delivery.

Naringin as Sustained Delivery Nanoparticles Ameliorates the Anti-inflammatory Activity in a Freund's Complete Adjuvant-Induced Arthritis Model.

Naringin (NAR), a naturally occurring essential flavonoid, present in grapefruit and Chinese herbal medicines, creates great interest in researchers due to its diverse biological and pharmacological activities. However, further development of NAR is hindered due to its poor water solubility and dissolution rates in GIT. To address these limitations, in this study, we report polymeric nanoparticles (NPs) of NAR (NAR-PLGA-NPs) for enhancing the oral NAR efficiency, with a biodegradable polymer (PLGA) to improve its absorption and bioavailability. NAR-PLGA-NPs were fabricated by a modified solvent emulsification–evaporation technique. Physicochemical properties were evaluated by SEM, particle size distribution, entrapment efficiency, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). In vitro drug release and ex vivo permeation studies were carried out in phosphate buffer (pH 6.8) for 24 h. Furthermore, in vivo anti-arthritic studies were performed on a mouse model, and the results were compared with free NAR. The modulation of inflammatory mediators was also evidently supported by docking studies. Optimized nanoformulation FN4 (NAR-PLGA-NPs) prepared with acetone–ethanol (2:1) as a solvent system in a combination of stabilizers, i.e., poloxamer-188 and sodium deoxylate (1:1), along with 2% PVA solution, was prepared. From size characterization studies, it was observed that nanoformulations possessed a low particle size (179.7 ± 2.05 nm), a low polydispersity index (0.206 ± 0.001), and a negative zeta potential (−9.18 ± 0.78 mV) with a maximum entrapment efficiency (74 ± 3.61%). The drug release followed a Korsmeyer–Peppas release kinetic model (anomalous non-Fickian diffusion), providing greater NAR release after lyophilization (82.11 ± 3.65%) drug release in pH 6.8 phosphate buffer for 24 h. Ex vivo permeation analysis through an isolated goat intestinal membrane revealed 80.02 ± 3.69% drug release in 24 h. Encapsulation of a drug into PLGA is well described by the results of FTIR, DSC, and XRD. Finally, the therapeutic efficacy of optimized FN4 (NAR-PLGA-NPs) and its possible application on RA were further confirmed in a Freund’s complete adjuvant-induced rat arthritic model as against free NAR at a dose of 20 mg/kg body wt. Our findings demonstrate that sustained action of NAR from optimized FN4 NPs with a rate-controlling polymeric carrier system exhibited prolonged circulation time and reduced arthritic inflammation, hence indicating the possibility as a novel strategy to secure the unpropitious biological interactions of hydrophobic NAR in a gastric environment.

Hydroxyethyl starch-new indocyanine green conjugates for enhanced cancer photodynamic therapy

In the present work, hydroxyethyl starch-new indocyanine green (HES-IR-820) conjugates were developed for enhanced cancer photodynamic therapy. HES-IR-820 conjugates were prepared by the condensation reaction between IR-820 and amino groups modified HES. HES-IR-820 conjugates with IR-820 loading content of 2.0% (HES-IR-8202.0) and 3.2% (HES-IR-8203.2) were prepared and characterized by 1H NMR, FT-IR, HPLC, and UV–Vis. HES-IR-8202.0 and HES-IR-8203.2 are monomolecular nanosized particles with hydrodynamic diameters of around 10 nm. HES-IR-8202.0 and HES-IR-8203.2 exhibit significantly enhanced stability in pH 7.4 PBS buffer and pH 7.4 PBS buffer containing 10% fetal bovine serum as compared to free IR-820. HES-IR-8202.0 and HES-IR-8203.2 show limited drug release in pH 7.4 and pH 5.0 PBS buffer. HES-IR-8202.0 and HES-IR-8203.2 exhibit enhanced singlet oxygen generation under 808 nm laser irradiation and reduced cellular uptake amount as compared to free IR-820. The cellular uptake pathway study reveals that the lipid raft-mediated endocytosis and macropinocytosis are involved in the cellular uptake of HES-IR-8202.0 and HES-IR-8203.2. Compared to free IR-820, HES-IR-8202.0 and HES-IR-8203.2 show reduced cytotoxicity, enhanced in vitro antitumor effect under 0.3 W/cm2 808 nm laser irradiation, and similar in vitro antitumor effect under 0.6 W/cm2 808 nm laser irradiation. HES-IR-820 conjugates show significant potential for cancer photodynamic therapy.

Coconut oil-based resveratrol nanoemulsion: Optimization using response surface methodology, stability assessment and pharmacokinetic evaluation

Phytochemicals are widely studied for therapeutic applications and nanostructured delivery systems for phytochemicals are under spotlight. Resveratrol is a promising candidate for neurodegenerative disorders. In the present study, we aimed to formulate nanoemulsion of resveratrol by ultrasonication process using response surface methodology. The effect of both formulation and ultrasonication process factors were studied for the nanoemulsification process using coconut oil, Pluronic-P107, and Cremophor EL. The time, intensity, and power of ultrasonication were selected as process factors. The globule size, PDI, and zeta potential were the responses selected. The concentrations of oil and surfactant and the intensity were found to significantly influence the globule size. The concentration of resveratrol in the optimized nanoemulsion formulation was 2.6442 mg/ml. The in vitro drug release in pH 6.8 phosphate buffer as well as in vitro permeation study on goat nasal mucosa proved the superiority of the nanoemulsion formulation. On intranasal administration in the rat at a resveratrol dose of 2 mg/kg, the brain targeting efficacy of the nanoemulsion formulation was high. Overall, this research provides the benefit of intake of resveratrol containing fruits and, its incorporation into nanoemulsions system could be a promising alternative for the management of Alzheimer's disease.

Development of Budesonide Oral Colon Specific Drug Delivery System using Interpolymer Complexation Method

Abstract: Background: Oral bioavailability of Budesonide is 10% due to its extensive first pass metabolism, its high volume of distribution and 85-90% of protein binding. Protection of drug release in stomach and targeting drug to colon which is an absorption site of drug is an attempt to improve therapeutic efficacy. The objective of this study was to develop interpolymer complex microspheres of Budesonide for oral colon specific drug delivery. Methods: Emulsion solvent evaporation method was used in the preparation of microspheres. Microspheres prepared at different polymer ratio and surfactant concentration were analysed for its mean particle size, surface morphology, flow property, drug release, % encapsulation efficiency. Results: Microspheres prepared with 3:5 polymer ratios F4 was optimized with respect to its % EE, in vitro drug release and percentage yield. Drug release from formulated tablets containing microspheres of 3:5 polymer ratios showed an extended release up to 12 h in pH buffer 7.4. Interpolymer complexation was confirmed by FT-IR studies, compatibility of drug with excipients by DSC indicated no significant changes with drug. SEM studies revealed formation of round microspheres with pervious and uneven surface. In vitro release data from microspheres was analysed by kinetic model fitting for mechanism of drug release. Microspheres showed 5-10% of drug release in pH 1.2 which was further prevented by formulating coated tablets of microspheres using cellulose acetate phthalate. Conclusion: Targeted colon specific drug delivery of Budenoside with extended release up to 12 h was successfully achieved by formulation of tablets containing microspheres prepared by interpolymer complexation technique. Key words: Budesonide, Colon Specific Delivery, Interpolymer Complexation, Microspheres, Cellulose Acetate phthalate.

Doxorubicin Loaded PLGA Nanoparticle with Cationic/Anionic Polyelectrolyte Decoration: Characterization, and Its Therapeutic Potency.

Optimized Doxorubicin hydrochloride (DOX) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (DPN) were prepared by controlling the water/oil distribution of DOX at different pH solutions and controlling the electrostatic interaction between DOX and different terminated-end PLGAs. Furthermore, cationic polyethylenimine (PEI) and anionic poly (acrylic acid) (PAA) were alternately deposited on DPN surface to form PEI-DPN (IDPN) and PAA-PEI-DPN (AIDPN) to enhance cancer therapy potency. Compared to DPN, IDPN exhibited a slower release rate in physiological conditions but PEI was demonstrated to increase the efficiency of cellular uptake and endo/lysosomal escape ability. AIDPN, with the outermost negatively charged PAA layer, still retained better endo/lysosomal escape ability compared to DPN. In addition, AIDPN exhibited the best pH-dependent release profile with 1.6 times higher drug release in pH 5.5 than in pH 7.4. Therefore, AIDPN with the characteristics of PEI and PAA simultaneously was the most optional cancer therapy choice within these three PLGA nanoparticles. As the proposed nanoparticles integrated optimal procedure factors, and possessed cationic and anionic outlayer, our drug delivery nanoparticles can provide an alternative solution to current drug delivery technologies.

Bursting the Virulence Traits of MDR Strain of Candida albicans Using Sodium Alginate-based Microspheres Containing Nystatin-loaded MgO/CuO Nanocomposites.

IntroductionCandida albicans is a major opportunistic pathogen that causes a wide range of human infections. Currently available therapeutic agents are limited for treating these fungal infections due to multidrug resistance as well as their nonbiodegradability, poor biocompatibility and toxicity. In order to battle these limitations, we have synthesized a polymeric system as microcarriers to deliver the antifungal drug. The objective of the present study was to immobilize MgO/CuO nanocomposite and nystatin-loaded MgO/CuO nanocomposites in nontoxic, nonimmunogenic, biodegradable and biocompatible sodium alginate microspheres for the first time.Materials and MethodsNanoparticle-loaded sodium alginate microspheres were prepared by ionotropic gelation technique using calcium chloride as a cross-linker. Synthesized microspheres were characterized using standard characterization techniques and were evaluated for biological activity against MDR strain of C. albicans.ResultsCharacterization of microspheres by Fourier-transform infrared spectroscopy confirmed loading of Nys-MgO/CuO NPs, scanning electron microscopy (SEM) revealed rough spherical beads with a highly porous surface having an average size in the range of 8–10 µm. X-ray diffraction (XRD) analyzed its semicrystalline structure. Entrapment efficiency of Nys-MgO/CuO NPs was 80% and release kinetic study revealed sustained and prolonged release of drug in pH 5.5. Flow cytometry analysis showed yeast cell death caused by Nys-MgO/CuO MS exhibits late apoptotic features. In cytotoxicity assay 5–14 mg of microspheres did not cause hemolysis. Microspheres reduced virulence traits of C. albicans such as germ tube and biofilm formation were compromised at concentration of 5 mg/mL. Antimicrobial assessment results revealed a pronounced inhibitory effect against C. albicans.ConclusionThe in vitro experiments have shown promising results based on good stability, Nys-MgO/CuO NP-encapsulated microspheres can be used as a prolonged controlled release system against MDR pathogenic C. albicans.

Development of Nicotinic Acid Controlled Release Tablets with Natural Phenolic Anti-oxidant Polymer by Encapsulation Technique

Nicotinic Acid (NA) is a cholesterol lowering agent used to treat dyslipidemia. Proanthocyanidins (PC) was selected as a drug and encapsulation material in which the later has a dual property of being a polymer as well as cholesterol lowering agent. The encapsulation of NA with different concentrations of (PC) was carried out by solvent evaporation technique. The encapsulated NA was converted to granules which were then compressed into tablets by wet granulation method. It was subjected to many pre-compression parameters evaluation such as flow properties, drug content and encapsulation efficiency. The tablets were evaluated for thickness, hardness, friability, &lt;em&gt;in vitro&lt;/em&gt; release studies, release kinetics and stability studies. The evaluated parameters of the formulations showed compliance with pharmacopoeial standards. The encapsulation efficiency was 99.73% and 99.52% of drug content. The FT-IR spectrum did not show interaction between drug and polymer. The drug release in pH 1.2 was lesser than in pH 6.8 buffer. The encapsulated product released drug in controlled manner in alkaline medium. The drug release was 97.1% and release was extended up to 12 hrs. The optimized batch underwent stability studies as per ICH guidelines. It can be concluded that among all the formulations the F5 can be considered as optimized formulation. The optimized formulations showed non-fickian diffusion mechanism of release.

Thioether-terminated triazole-bridged covalent organic framework for dual-sensitive drug delivery application

A novel thioether-terminated triazole bridge-containing covalent organic framework (TCOF) was constructed via a simple click chemistry between alkyne and azide monomers for dual-sensitive [pH and glutathione (GSH)] anticancer drug delivery systems. The synthesized TCOFs were crystalline in nature with a pore size of approximately 10–30 nm, as confirmed by powder X-ray diffraction spectroscopy and Brunauer–Emmett–Teller technique. Owing to the flexible nature of the synthesized COF, polyethylene glycol (PEG) modification was easily performed to yield a stable TCOF (TCOF-PEG) colloidal solution. Doxorubicin (DOX)-loaded TCOF-PEG (TCOF-DOX-PEG) exhibited sensitivity to lysosomal pH 5 and GSH environments. DOX release was four times higher under GSH environment (relative to pH 7.4) and three times higher under pH 5 condition because of the dynamic nature of triazole. In contrast, DOX-loaded COF without the triazole ring (I-COF) did not show any significant drug release in pH 7.4 and acidic pH; however, drug release was observed in GSH environment. MTT drug internalization data demonstrated sustained release of DOX from TCOF-DOX-PEGs. Finally, we demonstrated the utility of TCOF-PEG as an in vitro drug delivery system in HeLa cells. TCOF-DOX-PEG exhibited time-dependent release of DOX followed by internalization. Thus, the novel TCOF system reported here opens a new window in COF research for sensitive drug carrier systems.

Enhancing delayed release characteristics of chapparada avare seed starch

This study aims to evaluate the effects of pregelatinization in improving delayed release characteristics of native chapparada avare starch. Physicochemical properties and drug release characteristics were evaluated for the native and pregelatinized starches using established methods. The moisture content decreased from 12.13 ± 0.15% to 8.73 ± 0.12%, whereas amylose content (6.91 ± 0.06–21.13 ± 0.03), swelling power and water holding capacity (211.04 ± 0.03–513.03 ± 0.03) showed steady rise with pregelatinization time. The result of X ray diffraction pattern for pregelatinized starch, showed absence of 18.4° and 23.2° 2θ peaks thereby indicating reducing crystallinity, compared to native starch, whereas FESEM micrograph showed complete disruption of granular structure due to pregelatinization of native starch. The in vitro dissolution studies conducted in gastric and intestinal pH showed that tablets prepared with both native (NPL) and modified starch (PG15, PG20, PG 25), are gastro protective with less than 25% drug release in pH 1.2. In pH 6.8, PG 20 and PG 25 showed optimum drug release of 21.23 ± 0.54% and 19.40 ± 0.48% respectively in 6 h compared to 42.52 ± 0.21% release of NPL formulation, thereby indicating time based delayed drug release characteristics of over its native counterpart.

Preparation, characterization, and in vitro drug release behavior of thiolated alginate nanoparticles loaded budesonide as a potential drug delivery system toward inflammatory bowel diseases

For site-specific drug delivery in inflammatory bowel disease, reducible sodium alginate nanoparticles cross-linked with disulfide linkage were developed. Nanoparticles were synthesized in deionized water through self-assembly of amphiphilic thiolated sodium alginate Alg-Cys and subsequently produced cross-linking of disulfide bonds. TEM image showed a spherical core-shell configuration with a size of about 430 nm for the nanoparticles. Dynamic light scattering (DLS) showed high stability, narrow size distribution, and pH-dependent swelling transition for the nanoparticles. Cytotoxicity study showed that there was no evident cell inhibition among the nanoparticles. Also, the size of the nanoparticles increased in 10 mM glutathione (GSH) solution due to the cleavage of disulfides within their network structures. Compared to that in GSH-free buffer, there was a remarkable increase in drug release in pH 7.4 buffer with GSH from drug-loaded nanoparticles, indicating that the nanoparticles could be used for colon-specific drug delivery.

AlCl&lt;sub&gt;3&lt;/sub&gt; Cross-Linked and Spray Dried Carboxymethyl Sago Cellulose Microspheres as Potential Carriers for the Enteric Delivery

A semisynthetic polymer of carboxymethyl sago cellulose (CMSC) was synthesized from Malaysian sago biomass and further used in the development of drug delivery system. Recently, we have reported spray-dried carboxymethyl sago cellulose (CMSC) microspheres for enteric release and dissolution enhancement of piroxicam. In the present investigation, an attempt has been made to improve the enteric release property of CMSC microspheres using aluminium chloride as a cross-linker in the spray drying process and prednisolone as a model drug. CMSC microspheres loaded with prednisolone were prepared using a cross-linker concentration of 0%, 0.01%, 0.025% and 0.05%. All the drug-loaded microspheres were found to have high drug entrapment efficiencies (DEE) ranging from 99% to 106.1%. FT-IR spectroscopy has confirmed the cross-linking in CMSC microspheres as well as intact and amorphous nature of the entrapped drug. Field Emission Scanning Electron Microscope (FESEM) results have shown agglomeration of microspheres and the presence of drugs on the surface. Cross-linked microspheres have shown better efficiency than the uncross-linked microspheres in restricting drug release in stomach pH. Only about 5% of the loaded drug was released from cross-linked microspheres at pH 1.2 while 10% of the drug was released from uncross-linked microspheres. Also, cross-linked microspheres have exhibited faster drug release in pH 6.8 than the uncross-linked microspheres. Spray-dried and AlCl3 cross-linked CMSC microspheres have shown promising results in enteric drug delivery as well as dissolution enhancement.

FORMULATION AND EVALUATION OF METFORMIN HYDROCHLORIDE LOADED FLOATING MICROSPHERES

Objective: The main objective of this study was to develop and evaluate the eudragit and HPMC coated metformin hydrochloride floating microspheres, in which HPMC helps in floating and eudragit as a coating material for a site-specific drug release in a controlled manner and the active moiety metformin used as anti-hyperglycemic agent.&#x0D; Methods: The floating microsphere was prepared by the solvent evaporation method incorporating metformin as a model drug. The prepared floating microsphere were characterized for particle size, %yield, drug loading and entrapment efficiency, compatibility study, %buoyancy, surface morphology and In vitro drug release and release kinetics.&#x0D; Results: The result metformin loaded floating microsphere was successfully prepared and the particle size range from 397±23.22 to 595±15.82 µm, the entrapment efficiency range from 83.49±1.33 to 60.02±1.65% and drug loading capacity range from 14.3±0.54 to 13.31±0.47% and %buoyancy range from 85.67±0.58 to 80.67±1.15%. The FT-IR and X-RD analysis confirmed that no any interaction between drug and excipient, and surface morphology confirmed those particles are sphere. The floating microsphere show maximum 96% drug release in pH 0.1N HCL and follow the Korsmeyer peppas model of the super case-2 transport mechanism.&#x0D; Conclusion: These results suggest that metformin loaded floating microspheres could be retain in stomach for long time and give site specific drug release in controlled manner.

Poly-amino acids coated gold nanorod and doxorubicin for synergistic photodynamic therapy and chemotherapy in ovarian cancer cells.

In this work, we have successfully designed and formulated a doxorubicin-loaded polypeptide-based multilayer assembled gold nanorod (DH-GNR). We have hypothesized that near-infrared (NIR) laser irradiation of DH-GNR will combine the benefits of chemotherapy and photothermal therapy. The GNR was surface functionalized with poly-glutamic acid (PGA) and poly-l-Lysine (PLL) with a final layer of hyaluronic acid (HA) that could also serve as a targeting ligand toward the overexpressed CD44 receptors in ovarian cancer cells. The zigzag ζ potential of nanoparticle is a proof of successful assembly of alternative polymers on the GNR surface. NIR irradiation exhibited a burst release of drug in pH 7.4 and pH 5.0 buffer conditions. The combination of doxorubicin (DOX)-based chemotherapy and GNR-based photothermal therapy exhibited a synergistic effect in killing the SKOV3 cancer cells. DH-GNR(+NIR) induced a 82.5% apoptosis (combined early and late apoptosis) compared with only 35.2 and 38.5% for DOX or DH-GNR(−NIR) treated cell group. Results clearly suggest that the excessive reactive oxygen species (ROS) generation in DH-GNR (+NIR) might be responsible for the cell apoptosis and cell death. The promising anticancer effect of DH-GNR will be of great potential in the treatment of ovarian cancers and worth further development for treating other malignant tumors.