Displaying publications 1 - 20 of 198 in total

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  1. Effects of formulation development methods on the stability of model protein pharmaceuticals embedded in solid lipid matrices
    Tabbassum M, Zeeshan F
    Pharm Dev Technol, 2019 Jun;24(5):649-662.
    PMID: 30474456 DOI: 10.1080/10837450.2018.1551902
    This study was conducted to investigate the influence of formulation development methods on the stability (secondary structure, aggregation, and biological activity) of protein drugs embedded in lipid matrices. Catalase, horseradish peroxidase, and α-chymotrypsin were employed as model proteins, while Precirol® AT05 (glyceryl palmitostearate) was used as lipid matrix. Protein-loaded lipid matrices were prepared using melting and mixing and wet granulation methods. Attenuated total reflectance Fourier transform infrared (ATR FT-IR) spectroscopy, size exclusion chromatography (SEC) and biological activity analyses were performed. ATR FT-IR analysis indicated significant interference of the lipid with the protein amide-I band, which was eliminated using spectral subtraction. Wet granulation method induced more changes in protein secondary structure compared to melting and mixing method. SEC analysis gave evidence of protein aggregation for catalase upon adopting the wet granulation method. The biological activity of catalase was found to reduce significantly than other two proteins upon using wet granulation method, which might be ascribed to both secondary structure alterations and the formation of aggregates. Horseradish peroxidase and α-chymotrypsin did not form any soluble aggregates. In conclusion, melting and mixing method emerged as a better incorporation method compared to wet granulation because of better stability shown by the formulated proteins.
    Matched MeSH terms: Drug Liberation
  2. Evaluation of in vitro efficacy of docetaxel-loaded calcium carbonate aragonite nanoparticles (DTX-CaCO3NP) on 4T1 mouse breast cancer cell line
    Hammadi NI, Abba Y, Hezmee MNM, Razak ISA, Kura AU, Zakaria ZAB
    In Vitro Cell Dev Biol Anim, 2017 Dec;53(10):896-907.
    PMID: 28916966 DOI: 10.1007/s11626-017-0197-3
    Cockle shell-derived calcium carbonate nanoparticles have shown promising potentials as slow drug-releasing compounds in cancer chemotherapy. In this study, we evaluated the in vitro efficacy of docetaxel (DTX)-loaded CaCO3NP on 4T1 cell line. This was achieved by evaluating the following: cytotoxicity using MTT assay, fluorescence imaging, apoptosis with Annexin V assay, cell cycle analysis, scanning (SEM) and transmission electron microscopy (TEM), and scratch assay. Based on the results, DTX-CaCO3NP with a DTX concentration of 0.5 μg/mL and above had comparable cytotoxic effects with free DTX at 24 h, while all concentrations had similar cytotoxic effect on 4T1 cells at 48 and 72 h. Fluorescence and apoptosis assay showed a higher (p 
    Matched MeSH terms: Drug Liberation
  3. Formulation of a Sustained Release Docetaxel Loaded Cockle Shell-Derived Calcium Carbonate Nanoparticles against Breast Cancer
    Hammadi NI, Abba Y, Hezmee MNM, Razak ISA, Jaji AZ, Isa T, et al.
    Pharm Res, 2017 06;34(6):1193-1203.
    PMID: 28382563 DOI: 10.1007/s11095-017-2135-1
    PURPOSE: Here, we explored the formulation of a calcium carbonate nanoparticle delivery system aimed at enhancing docetaxel (DTX) release in breast cancer.

    METHODS: The designed nano- anticancer formulation was characterized thorough X-ray diffraction (XRD), Fourier transformed infrared (FTIR), transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM) and Brunauer-Emmett-Teller (BET) methods. The nano- anticancer formulation (DTX- CaCO3NP) was evaluated for drug delivery properties thorough in vitro release study in human body simulated solution at pH 7.4 and intracellular lysosomal pH 4.8.

    RESULTS: Characterization revealed the successful synthesis of DTX- CaCO3NP, which had a sustained release at pH 7.4. TEM showed uniformly distributed pleomorphic shaped pure aragonite particles. The highest entrapment efficiency (96%) and loading content (11.5%) were obtained at docetaxel to nanoparticles ratio of 1:4. The XRD patterns revealed strong crystallizations in all the nanoparticles formulation, while FTIR showed chemical interactions between the drug and nanoparticles with negligible positional shift in the peaks before and after DTX loading. BET analysis showed similar isotherms before and after DTX loading. The designed DTX- CaCO3NP had lower (p  0.05) effects at 48 h and 72 h. However, the DTX- CaCO3NP released less than 80% of bond DTX at 48 and 72 h but showed comparable effects with free DTX.

    CONCLUSIONS: The results showed that the developed DTX- CaCO3NP released DTX slower at pH 7.4 and had comparable cytotoxicity with free DTX at 48 and 72 h in MCF-7 cells.

    Matched MeSH terms: Drug Liberation
  4. Fulltext Pharmaco-Technical Evaluation of Statistically Formulated and Optimized Dual Drug-Loaded Silica Nanoparticles for Improved Antifungal Efficacy and Wound Healing
    Masood A, Maheen S, Khan HU, Shafqat SS, Irshad M, Aslam I, et al.
    ACS Omega, 2021 Mar 30;6(12):8210-8225.
    PMID: 33817480 DOI: 10.1021/acsomega.0c06242
    The current research aimed at designing mesoporous silica nanoparticles (MSNs) for a controlled coadministration of salicylic acid (SA) and ketoconazole (KCZ) to effectively treat highly resistant fungal infections. The sol-gel method was used to formulate MSNs, which were further optimized using central composite rotatable design (CCRD) by investigating mathematical impact of independent formulation variables such as pH, stirring time, and stirring speed on dependent variables entrapment efficiency (EE) and drug release. The selected optimized MSNs and pure drugs were subjected to comparative in vitro/in vivo antifungal studies, skin irritation, cytotoxicity, and histopathological evaluations. The obtained negatively charged (-23.1), free flowing spherical, highly porous structured MSNs having a size distribution of 300-500 nm were suggestive of high storage stability and improved cell proliferation due to enhanced oxygen supply to cells. The physico-chemical evaluation of SA/KCZ-loaded MSNs performed through powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA) indicates absolute lack of any interaction between formulation components and successful encapsulation of both drugs in MSNs. The EESA, EEKCZ, SA release, and KCZ release varied significantly from 34 to 89%, 36 to 85%, 39 to 88%, and 43 to 90%, respectively, indicating the quadratic impact of formulation variables on obtained MSNs. For MSNs, the skin tolerability and cell viability percentage rate were also having an extraordinary advantage over suspension of pure drugs. The optimized SA/KCZ-loaded MSNs demonstrated comparatively enhanced in vitro/in vivo antifungal activities and rapid wound healing efficacy in histopathological evaluation without any skin irritation impact, suggesting the MSNs potential for the simultaneous codelivery of antifungal and keratolyic agents in sustained release fashion.
    Matched MeSH terms: Drug Liberation
  5. Binding Characterization of Aptamer-Drug Layered Microformulations and In Vitro Release Assessment
    Tan KX, Danquah MK, Pan S, Yon LS
    J Pharm Sci, 2019 09;108(9):2934-2941.
    PMID: 31002808 DOI: 10.1016/j.xphs.2019.03.037
    Efficient delivery of adequate active ingredients to targeted malignant cells is critical, attributing to recurrent biophysical and biochemical challenges associated with conventional pharmaceutical delivery systems. These challenges include drug leakage, low targeting capability, high systemic cytotoxicity, and poor pharmacokinetics and pharmacodynamics. Targeted delivery system is a promising development to deliver sufficient amounts of drug molecules to target cells in a controlled release pattern mode. Aptameric ligands possess unique affinity targeting capabilities which can be exploited in the design of high pay-load drug formulations to navigate active molecules to the malignant sites. This study focuses on the development of a copolymeric and multifunctional drug-loaded aptamer-conjugated poly(lactide-co-glycolic acid)-polyethylenimine (PLGA-PEI) (DPAP) delivery system, via a layer-by-layer synthesis method, using a water-in-oil-in-water double emulsion approach. The binding characteristics, targeting capability, biophysical properties, encapsulation efficiency, and drug release profile of the DPAP system were investigated under varying conditions of ionic strength, polymer composition and molecular weight (MW), and degree of PEGylation of the synthetic core. Experimental results showed increased drug release rate with increasing buffer ionic strength. DPAP particulate system obtained the highest drug release of 50% at day 9 at 1 M NaCl ionic strength. DPAP formulation, using PLGA 65:35 and PEI MW of ∼800 Da, demonstrated an encapsulation efficiency of 78.93%, and a loading capacity of 0.1605 mg bovine serum albumin per mg PLGA. DPAP (PLGA 65:35, PEI MW∼25 kDa) formulation showed a high release rate with a biphasic release profile. Experimental data depicted a lower targeting power and reduced drug release rate for the PEGylated DPAP formulations. The outcomes from the present study lay the foundation to optimize the performance of DPAP system as an effective synthetic drug carrier for targeted delivery.
    Matched MeSH terms: Drug Liberation
  6. Novel docetaxel chitosan-coated PLGA/PCL nanoparticles with magnified cytotoxicity and bioavailability
    Badran MM, Alomrani AH, Harisa GI, Ashour AE, Kumar A, Yassin AE
    Biomed Pharmacother, 2018 Oct;106:1461-1468.
    PMID: 30119220 DOI: 10.1016/j.biopha.2018.07.102
    In the present study, docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) nanoparticles were successfully prepared and coated with chitosan (CS). The prepared nanoparticles (NPs) were evaluated for their particle size, zeta potential, particle morphology, drug entrapment efficiency (EE%), and in vitro drug release profile. The anticancer activity of DTX-loaded NPs was assessed in human HT29 colon cancer cell line utilizing MTT assay. The pharmacokinetics of DTX-loaded NPs was monitored in Wistar rats in comparison to DTX solution. The prepared NPs exhibited particle sizes in the range 177.1 ± 8.2-287.6 ± 14.3 nm. CS decorated NPs exhibited a significant increase in particle size and a switch of zeta potential from negative to positive. In addition, high EE% values were obtained for CS coated PCL NPs and PLGA NPs as 67.1 and 76.2%, respectively. Moreover, lowering the rate of DTX in vitro release was achieved within 48 h by using CS coated NPs. Furthermore, a tremendous increase in DTX cytotoxicity was observed by CS-decorated PLGA NPs compared to all other NPs including DTX-free-NPs and pure DTX. The in vivo study revealed significant enhancement in DTX bioavailability from CS-decorated PLGA NPs with more than 4-fold increase in AUC compared to DTX solution. In conclusion, CS-decorated PLGA NPs are a considerable DTX-delivery carrier with magnificent antitumor efficacy.
    Matched MeSH terms: Drug Liberation
  7. Erlotinib-loaded carboxymethyl temarind gum semi-interpenetrating nanocomposites
    Bera H, Abbasi YF, Lee Ping L, Marbaniang D, Mazumder B, Kumar P, et al.
    Carbohydr Polym, 2020 Feb 15;230:115664.
    PMID: 31887927 DOI: 10.1016/j.carbpol.2019.115664
    Erlotinib-loaded carboxymethyl temarind gum-g-poly(N-isopropylacrylamide)-montmorillonite based semi-IPN nanocomposites were synthesized and characterized for their in vitro performances for lung cancer therapy. The placebo matrices exhibited outstanding biodegradability and pH-dependent swelling profiles. The molar mass (M¯ c) between the crosslinks of these composites was declined with temperature. The solid state characterization confirmed the semi-IPN architecture of these scaffolds. The corresponding drug-loaded formulations displayed excellent drug-trapping capacity (DEE, 86-97 %) with acceptable zeta potential (-16 to -13 mV) and diameter (967-646 nm). These formulations conferred sustained drug elution profiles (Q8h, 77-99 %) with an initial burst release. The drug release profile of the optimized formulation (F-3) was best fitted in the first order kinetic model with Fickian diffusion driven mechanism. The mucin adsorption to F-3 followed Langmuir isotherms. The results of MTT assay, AO/EB staining and confocal analyses revealed that the ERL-loaded formulation suppressed A549 cell proliferation and induced apoptosis more effectively than pristine drug.
    Matched MeSH terms: Drug Liberation
  8. Design of oral intestinal-specific alginate-vitexin nanoparticulate system to modulate blood glucose level of diabetic rats
    Shaedi N, Naharudin I, Choo CY, Wong TW
    Carbohydr Polym, 2021 Feb 15;254:117312.
    PMID: 33357875 DOI: 10.1016/j.carbpol.2020.117312
    Vitexin of Ficus deltoidea exhibits intestinal α-glucosidase inhibitory and blood glucose lowering effects. This study designs oral intestinal-specific alginate nanoparticulate system of vitexin. Nanospray-dried alginate, alginate/stearic acid and alginate-C18 conjugate nanoparticles were prepared. Stearic acid was adopted to hydrophobize the matrix and minimize premature vitexin release in stomach, whereas C-18 conjugate as immobilized fatty acid to sustain hydrophobic effect and drug release. Nanoparticles were compacted with polyethylene glycol (PEG 3000, 10,000 and 20,000). The physicochemical, drug release, in vivo blood glucose lowering and intestinal vitexin content of nanoparticles and compact were determined. Hydrophobization of alginate nanoparticles promoted premature vitexin release. Compaction of nanoparticles with PEG minimized vitexin release in the stomach, with stearic acid loaded nanoparticles exhibiting a higher vitexin release in the intestine. The introduction of stearic acid reduced vitexin-alginate interaction, conferred alginate-stearic acid mismatch, and dispersive stearic acid-induced particle breakdown with intestinal vitexin release. Use of PEG 10,000 in compaction brought about PEG-nanoparticles interaction that negated initial vitexin release. The PEG dissolution in intestinal phase subsequently enabled particle breakdown and vitexin release. The PEG compacted nanoparticles exhibited oral intestinal-specific vitexin release, with positive blood glucose lowering and enhanced intestinal vitexin content in vivo.
    Matched MeSH terms: Drug Liberation
  9. In Vitro Drug Dissolution/Permeation Testing of Nanocarriers for Skin Application: a Comprehensive Review
    Sheshala R, Anuar NK, Abu Samah NH, Wong TW
    AAPS PharmSciTech, 2019 Apr 15;20(5):164.
    PMID: 30993407 DOI: 10.1208/s12249-019-1362-7
    This review highlights in vitro drug dissolution/permeation methods available for topical and transdermal nanocarriers that have been designed to modulate the propensity of drug release, drug penetration into skin, and permeation into systemic circulation. Presently, a few of USFDA-approved in vitro dissolution/permeation methods are available for skin product testing with no specific application to nanocarriers. Researchers are largely utilizing the in-house dissolution/permeation testing methods of nanocarriers. These drug release and permeation methods are pending to be standardized. Their biorelevance with reference to in vivo plasma concentration-time profiles requires further exploration to enable translation of in vitro data for in vivo or clinical performance prediction.
    Matched MeSH terms: Drug Liberation
  10. Fulltext Design of polysaccharidic nano-in-micro soft agglomerates as primary oral drug delivery vehicle for colon-specific targeting
    Musa N, Wong TW
    Carbohydr Polym, 2020 Nov 01;247:116673.
    PMID: 32829801 DOI: 10.1016/j.carbpol.2020.116673
    Microencapsulation of polysaccharidic nanoparticles is met with nanoscale and biological performance changes. This study designs soft agglomerates as nanoparticle vehicle without nanoparticles undergoing physical processes that alter their geometry. The nanoparticles were made of high molecular weight chitosan/pectin with covalent 5-fluorouracil/folate. Nanoparticle aggregation vehicle was prepared from low molecular weight chitosan. The nanoparticles and aggregation vehicle were blended in specific weight ratios to produce soft agglomerates. Nanoparticles alone are unable to agglomerate. Adding aggregation vehicle (< 2 μm) promoted soft agglomeration with nanoparticles deposited onto its surfaces with minimal binary coalescence. The large and rough-surfaced aggregation vehicle promoted nanoparticles deposition and agglomeration. A rounder vehicle allowed assembly of nanoparticles-on-aggregation vehicle into agglomerates through interspersing smaller between larger populations. Soft agglomeration reduced early drug release, and was responsive to intracapsular sodium alginate coat to further sustain drug release. The soft agglomerates can serve as a primary oral colon-specific vehicle.
    Matched MeSH terms: Drug Liberation
  11. Design of multi-particulate "Dome matrix" with sustained-release melatonin and delayed-release caffeine for jet lag treatment
    Razali S, Bose A, Chong PW, Benetti C, Colombo P, Wong TW
    Int J Pharm, 2020 Sep 25;587:119618.
    PMID: 32673769 DOI: 10.1016/j.ijpharm.2020.119618
    Multi-particulate Dome matrix with sustained-release melatonin and delayed-release caffeine was designed to restore jet lag sleep-wake cycle. The polymeric pellets were produced using extrusion-spheronization technique and fluid-bed coated when applicable. The compact and Dome module were produced by compressing pellets with cushioning agent. Dome matrix was assembly of modules with pre-determined compact formulation and drug release characteristics. The physicochemical and in vivo pharmacokinetics of delivery systems were examined. Melatonin loaded alginate/chitosan-less matrix exhibited full drug release within 8 h gastrointestinal transit with low viscosity hydroxypropymethylcellulose as cushioning agent. The cushioning agent reduced burst drug release and omission of alginate-chitosan enabled full drug release. Delayed-release alginate-chitosan caffeine matrix was not attainable through polymer coating due to premature coat detachment. Admixing of cushioning agent high viscosity hydroxypropylmethylcellulose and high viscosity ethylcellulose (9:1 wt ratio) with coat-free caffeine loaded particulates introduced delayed-release response via hydroxypropylmethylcellulose swelled in early dissolution phase and ethylcellulose sustained matrix hydrophobicity at prolonged phase. The caffeine was released substantially in colonic fluid in response to matrix polymers being degraded by rat colonic content. Dome matrix with dual drug release kinetics and modulated pharmacokinetics is produced to introduce melatonin-induced sleep phase then caffeine-stimulated wake phase.
    Matched MeSH terms: Drug Liberation
  12. Critical physicochemical and biological attributes of nanoemulsions for pulmonary delivery of rifampicin by nebulization technique in tuberculosis treatment
    Shah K, Chan LW, Wong TW
    Drug Deliv, 2017 Nov;24(1):1631-1647.
    PMID: 29063794 DOI: 10.1080/10717544.2017.1384298
    The study investigated aerosolization, pulmonary inhalation, intracellular trafficking potential in macrophages and pharmacokinetics profiles of rifampicin-oleic acid first-generation nanoemulsion and its respective chitosan- and chitosan-folate conjugate-decorated second and third-generation nanoemulsions, delivered via nebulization technique. The nanoemulsions were prepared by conjugate synthesis and spontaneous emulsification techniques. They were subjected to physicochemical, drug release, aerosolization, inhalation, cell culture and pharmacokinetics analysis. The nanoemulsions had average droplet sizes of 40-60 nm, with narrow polydispersity indices. They exhibited desirable pH, surface tension, viscosity, refractive index, density and viscosity attributes for pulmonary rifampicin administration. All nanoemulsions demonstrated more than 95% aerosol output and inhalation efficiency greater than 75%. The aerosol output, aerosolized and inhaled fine particle fractions were primarily governed by the size and surface tension of nanoemulsions in an inverse relationship. The nanoemulsions were found to be safe with third-generation nanoemulsion exhibiting higher cell internalization potential, reduced plasma drug concentration, and higher lung drug content.
    Matched MeSH terms: Drug Liberation
  13. Fulltext The Potential Anticancer Activity of 5-Fluorouracil Loaded in Cellulose Fibers Isolated from Rice Straw
    Yusefi M, Shameli K, Jahangirian H, Teow SY, Umakoshi H, Saleh B, et al.
    Int J Nanomedicine, 2020;15:5417-5432.
    PMID: 32801697 DOI: 10.2147/IJN.S250047
    INTRODUCTION: Green-based materials have been increasingly studied to circumvent off-target cytotoxicity and other side-effects from conventional chemotherapy.

    MATERIALS AND METHODS: Here, cellulose fibers (CF) were isolated from rice straw (RS) waste by using an eco-friendly alkali treatment. The CF network served as an anticancer drug carrier for 5-fluorouracil (5-FU). The physicochemical and thermal properties of CF, pure 5-FU drug, and the 5-FU-loaded CF (CF/5-FU) samples were evaluated. The samples were assessed for in vitro cytotoxicity assays using human colorectal cancer (HCT116) and normal (CCD112) cell lines, along with human nasopharyngeal cancer (HONE-1) and normal (NP 460) cell lines after 72-hours of treatment.

    RESULTS: XRD and FTIR revealed the successful alkali treatment of RS to isolate CF with high purity and crystallinity. Compared to RS, the alkali-treated CF showed an almost fourfold increase in surface area and zeta potential of up to -33.61 mV. SEM images illustrated the CF network with a rod-shaped structure and comprised of ordered aggregated cellulose. TGA results proved that the thermal stability of 5-FU increased within the drug carrier. Based on UV-spectroscopy measurements for 5-FU loading into CF, drug loading encapsulation efficiency was estimated to be 83 ±0.8%. The release media at pH 7.4 and pH 1.2 showed a maximum drug release of 79% and 46%, respectively, over 24 hours. In cytotoxicity assays, CF showed almost no damage, while pure 5-FU killed most of the both normal and cancer cells. Impressively, the drug-loaded sample of CF/5-FU at a 250 µg/mL concentration demonstrated a 58% inhibition against colorectal cancer cells, but only a 23% inhibition against normal colorectal cells. Further, a 62.50 µg/mL concentration of CF/5FU eliminated 71% and 39% of nasopharyngeal carcinoma and normal nasopharyngeal cells, respectively.

    DISCUSSION: This study, therefore, showed the strong potential anticancer activity of the novel CF/5-FU formulations, warranting their further investigation.

    Matched MeSH terms: Drug Liberation
  14. Kondogogu gum-Zn(+2)-pectinate emulgel matrices reinforced with mesoporous silica for intragastric furbiprofen delivery
    Bera H, Nadimpalli J, Kumar S, Vengala P
    Int J Biol Macromol, 2017 Nov;104(Pt A):1229-1237.
    PMID: 28688948 DOI: 10.1016/j.ijbiomac.2017.07.027
    Flurbiprofen (FLU), a non-steroidal anti-inflammatory drug, exhibits limited clinical response due to its poor physicochemical properties. This study aimed at developing reliable drug carriers for intrgastric FLU delivery with a view to improve biopharmaceutical characteristics of drug and modulate its release in a controlled manner. In this context, FLU-loaded kondogogu gum (KG)-Zn(+2)-low methoxyl (LM) pectinate emulgel matrices reinforced with calcium silicate (CS) were accomplished by ionotropic gelation technique employing zinc acetate as cross-linker and characterized for their in vitro performances. All the formulations demonstrated excellent drug encapsulation efficiency (DEE, 46-87%) and sustained drug release behavior (Q7h, 70-91%). These quality attributes were remarkably influenced by polymer-blend (LM pectin:KG) ratios, low-density oil types and CS inclusion. The drug release profile of the FLU-loaded optimized matrices (F-7) was best fitted in Korsmeyer-Peppas model with Fickian diffusion driven mechanism. It also conferred excellent in vitro gastroretention capabilities. Moreover, the drug-excipient compatibility, alteration of crystallinity and thermal behavior of drug and surface morphology of matrices were evidenced with the results of FTIR, XRD, DSC and SEM analyses, respectively. Thus, the newly developed matrices are appropriate for sustained intragastric FLU delivery and simultaneous zinc supplementation for effective inflammation and arthritis management.
    Matched MeSH terms: Drug Liberation
  15. Carboxymethyl fenugreek galactomannan-gellan gum-calcium silicate composite beads for glimepiride delivery
    Bera H, Mothe S, Maiti S, Vanga S
    Int J Biol Macromol, 2018 Feb;107(Pt A):604-614.
    PMID: 28916379 DOI: 10.1016/j.ijbiomac.2017.09.027
    Novel carboxymethyl fenugreek galactomannan (CFG)-gellan gum (GG)-calcium silicate (CS) composite beads were developed for controlled glimepiride (GLI) delivery. CFG having degree of carboxymethylation of 0.71 was synthesized and characterized by FTIR, DSC and XRD analyses. Subsequently, GLI-loaded hybrids were accomplished by ionotropic gelation technique employing Ca+2/Zn+2/Al+3 ions as cross-linkers. All the formulations demonstrated excellent drug encapsulation efficiency (DEE, 48-97%) and sustained drug release behaviour (Q8h, 62-94%). These quality attributes were remarkably influenced by polymer-blend (GG:CFG) ratios, cross-linker types and CS inclusion. The drug release profile of the optimized formulation (F-6) was best fitted in zero-order model with anomalous diffusion driven mechanism. It also conferred excellent ex vivo mucoadhesive property and considerable hypoglycemic effect in streptozotocin-induced diabetic rats. Furthermore, the beads were characterized for drug-excipients compatibility, drug crystallinity, thermal behaviour and surface morphology. Thus, the developed hybrid matrices are appropriate for controlled delivery of GLI for Type 2 diabetes management.
    Matched MeSH terms: Drug Liberation
  16. The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery
    Ma Y, Fuchs AV, Boase NR, Rolfe BE, Coombes AG, Thurecht KJ
    Eur J Pharm Biopharm, 2015 Aug;94:393-403.
    PMID: 26117186 DOI: 10.1016/j.ejpb.2015.06.014
    Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan-hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8h to 24h post-administration compared to the free NPs, due to a NP 'guarding' effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems.
    Matched MeSH terms: Drug Liberation
  17. In situ forming phase-inversion implants for sustained ocular delivery of triamcinolone acetonide
    Sheshala R, Hong GC, Yee WP, Meka VS, Thakur RRS
    Drug Deliv Transl Res, 2019 04;9(2):534-542.
    PMID: 29484530 DOI: 10.1007/s13346-018-0491-y
    The objectives of this study were to develop biodegradable poly-lactic-co-glycolic acid (PLGA) based injectable phase inversion in situ forming system for sustained delivery of triamcinolone acetonide (TA) and to conduct physicochemical characterisation including in vitro drug release of the prepared formulations. TA (at 0.5%, 1% and 2.5% w/w loading) was dissolved in N-methyl-2-pyrrolidone (NMP) solvent and then incorporated 30% w/w PLGA (50/50 and 75/25) polymer to prepare homogenous injectable solution. The formulations were evaluated for rheological behaviour using rheometer, syringeability by texture analyser, water uptake and rate of implant formation by optical coherence tomography (OCT) microscope. Phase inversion in situ forming formulations were injected into PBS pH 7.3 to form an implant and release samples were collected and analysed for drug content using a HPLC method. All formulations exhibited good syringeability and rheological properties (viscosity: 0.19-3.06 Pa.s) by showing shear thinning behaviour which enable them to remain as free-flowing solution for ease administration. The results from OCT microscope demonstrated that thickness of the implants were increased with the increase in time and the rate of implant formation indicated the fast phase inversion. The drug release from implants was sustained over a period of 42 days. The research findings demonstrated that PLGA/NMP-based phase inversion in situ forming implants can improve compliance in patient's suffering from ocular diseases by sustaining the drug release for a prolonged period of time and thereby reducing the frequency of ocular injections.
    Matched MeSH terms: Drug Liberation
  18. Fulltext Green Synthesized Montmorillonite/Carrageenan/Fe3O4 Nanocomposites for pH-Responsive Release of Protocatechuic Acid and Its Anticancer Activity
    Yew YP, Shameli K, Mohamad SE, Lee KX, Teow SY
    Int J Mol Sci, 2020 Jul 09;21(14).
    PMID: 32659939 DOI: 10.3390/ijms21144851
    Discovery of a novel anticancer drug delivery agent is important to replace conventional cancer therapies which are often accompanied by undesired side effects. This study demonstrated the synthesis of superparamagnetic magnetite nanocomposites (Fe3O4-NCs) using a green method. Montmorillonite (MMT) was used as matrix support, while Fe3O4 nanoparticles (NPs) and carrageenan (CR) were used as filler and stabilizer, respectively. The combination of these materials resulted in a novel nanocomposite (MMT/CR/Fe3O4-NCs). A series of characterization experiments was conducted. The purity of MMT/CR/Fe3O4-NCs was confirmed by X-ray diffraction (XRD) analysis. High resolution transmission electron microscopy (HRTEM) analysis revealed the uniform and spherical shape of Fe3O4 NPs with an average particle size of 9.3 ± 1.2 nm. Vibrating sample magnetometer (VSM) analysis showed an Ms value of 2.16 emu/g with negligible coercivity which confirmed the superparamagnetic properties. Protocatechuic acid (PCA) was loaded onto the MMT/CR/Fe3O4-NCs and a drug release study showed that 15% and 92% of PCA was released at pH 7.4 and 4.8, respectively. Cytotoxicity assays showed that both MMT/CR/Fe3O4-NCs and MMT/CR/Fe3O4-PCA effectively killed HCT116 which is a colorectal cancer cell line. Dose-dependent inhibition was seen and the killing was enhanced two-fold by the PCA-loaded NCs (IC50-0.734 mg/mL) compared to the unloaded NCs (IC50-1.5 mg/mL). This study highlights the potential use of MMT/CR/Fe3O4-NCs as a biologically active pH-responsive drug delivery agent. Further investigations are warranted to delineate the mechanism of cell entry and cancer cell killing as well as to improve the therapeutic potential of MMT/CR/Fe3O4-NCs.
    Matched MeSH terms: Drug Liberation/drug effects
  19. Fulltext In Vitro Performance of Dutasteride-Nanostructured Lipid Carriers Coated with Lauric Acid-Chitosan Oligomer for Dermal Delivery
    Noor NM, Abdul-Aziz A, Sheikh K, Somavarapu S, Taylor KMG
    Pharmaceutics, 2020 Oct 20;12(10).
    PMID: 33092119 DOI: 10.3390/pharmaceutics12100994
    Dutasteride, licensed as an oral medicine for the treatment of benign prostatic hypoplasia, has been investigated as a treatment for androgenic alopecia. In this study, the potential for dustasteride to be delivered topically in order to reduce systemic exposure, irritation of the skin, and also cytotoxicity was explored. Chitosan oligomer (CSO) was successfully synthesised with lauric acid as a coating for a dutasteride-loaded nanostructured lipid carriers (DST-NLCs) system. DST-NLCs were prepared using a combination of melt-dispersion and ultrasonication. These negatively charged NLCs (-18.0 mV) had a mean particle size of ~184 nm, which was not significantly increased (p > 0.05) when coated with lauric acid-chitosan oligomer (CSO-LA), whilst the surface charge changed to positive (+24.8 mV). The entrapment efficiency of DST-NLCs was 97%, and coated and uncoated preparations were physically stable for up to 180 days at 4-8 °C. The drug release was slower from DST-NLCs coated with CSO-LA than from uncoated NLCs, with no detectable drug permeation through full-thickness pig ear skin from either preparation. Considering the cytotoxicity, the IC50 values for the DST-NLCs, coated and uncoated with CSO-LA were greater than for dutasteride alone (p < 0.05). DST-NLCs and empty NLCs coated with CSO-LA at 25 µM increased the cell proliferation compared to the control, and no skin irritation was observed when the DST-NLC formulations were tested using EpiDerm™. The cell and skin uptake studies of coated and uncoated NLCs incorporating the fluorescent marker Coumarin-6 showed the time-dependent uptake of Coumarin-6. Overall, the findings suggest that DST-NLCs coated with CSO-LA represent a promising formulation strategy for dutasteride delivery for the treatment of androgenic alopecia, with a reduced cytotoxicity compared to that of the drug alone and lower irritancy than an ethanolic solution of dutasteride.
    Matched MeSH terms: Drug Liberation
  20. From formulation of acrylamide-based hydrogels to their optimization for drug release using response surface methodology
    Sabbagh F, Muhamad II, Nazari Z, Mobini P, Taraghdari SB
    Mater Sci Eng C Mater Biol Appl, 2018 Nov 01;92:20-25.
    PMID: 30184743 DOI: 10.1016/j.msec.2018.06.022
    This study conducted on the structure of modified acrylamide-based hydrogel by synthesizing the nano composites. The hydrogels employed in this study were provided through a combination of acrylamide monomers, sodium carboxymethyl cellulose (NaCMC) and magnesium oxide (MgO) nanoparticles by crosslinking polymerization. N,N,N',N'-tetramethylethylenediamine and ammonium persulfate as the initiator was applied in the structure of the polymer. Findings of the study considered the nano composites consisting of MgO have the highest swelling ratio compared to pure Aam hydrogels. Thus, MgO is an appropriate nanoparticle to be used in the nano composites. Response surface methodology (RSM) based on a central composite design (CCD Design) was applied to optimize the preparation variables of a hydrogel consisted of MgO, NaCMC. With the swelling ratio for acrylamide-based hydrogel as the response, the effects of two variables, i.e. MgO and NaCMC were investigated. The effects of pH, temperature, MgO, and NaCMC on the drug release were investigated using the CCD design. The predicted appropriate drug release conditions for the hydrogel at the highest rate of temperature (37.50 °C) and pH: 4.10, is at its highest value, while the lower drug release is at temperature 38 °C and pH 3.50. With the desired value of MgO (0.01 g) and amount of NaCMC (0.1 g).
    Matched MeSH terms: Drug Liberation
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