Enhanced Drug Loading Capacity Research Articles

Biotin-stapled mixed micelles of lapatinib: Unleashing apoptosis power in triple-negative breast cancer

The treatment options currently offered for triple-negative breast cancer (TNBC) encounter numerous obstacles, including disappointing overall survival rates, unavoidable side effects, and the development of drug resistance. Additionally, there is a growing need for nutrients, like vitamins (e.g., biotin), to sustain the unregulated growth of TNBC cells. Hence, targeted therapy (LPT B-MM) for enhancing the treatment of TNBC was explored which encompassed hydrophobized [using α-TOS (α-Tocopheryl succinate] Pluronic-based mixed micelles having inherent sodium-dependent multivitamin transporter (SMVT) targeting (biotin-stapled) ability. LPT B-MM had optimal size (210.72± 25.88 nm), PDI (0.272± 0.023), and enhanced drug loading capacity (∼13.31± 2.12%). Transmission electron microscopy validated the spherical shape of these micelles. In vitro release studies demonstrated drug release in a sustained manner without the risk of hemolysis. Importantly, LPT B-MM displayed heightened cellular uptake, increased cytotoxicity, a lower IC50 value, elevated reactive oxygen species, induced mitochondrial membrane depolarization, and a greater apoptosis index in TNBC cell lines compared to free LPT. This study highlights the considerable potential of LPT B-MM to induce apoptosis, showcasing its promise in enhancing payload capabilities and enabling SMVT specific targeting within the context of TNBC. LPT B-MM demonstrated the synergistic effects of LPT and α-TOS in inducing apoptosis in TNBC cells, leading to enhanced therapeutic efficacy. This novel combination therapy offers a promising strategy for improving treatment outcomes in TNBC patients and represents a significant advancement in the field of TNBC therapy.

Injectable Inflammation-Responsive Hydrogels for Microenvironmental Regulation of Intervertebral Disc Degeneration.

Chronic local inflammation and excessive cell apoptosis in nucleus pulposus (NP) tissue are the main causes of intervertebral disc degeneration (IDD). Stimuli-responsive hydrogels have great potential in the treatment of IDD by facilitating localized and controlled drug delivery. Herein, an injectable drug-loaded dual stimuli-responsive adhesive hydrogel for microenvironmental regulation of IDD, is developed. The gelatin methacryloyl is functionalized with phenylboronic acid groups to enhance drug loading capacity and enable dual stimuli-responsive behavior, while the incorporation of oxidized hyaluronic acid further improves the adhesive properties. The prepared hydrogel exhibits an enhanced drug loading capacity for diol-containing drugs, pH- and reactive oxygen species (ROS)-responsive behaviors, excellent radical scavenging efficiency, potent antibacterial activity, and favorable biocompatibility. Furthermore, the hydrogel shows a beneficial protective efficacy on NP cells within an in vitro oxidative stress microenvironment. The in vivo results demonstrate the hydrogel's excellent therapeutic effect on treating IDD by maintaining water retention, restoring disc height, and promoting NP regeneration, indicating that this hydrogel holds great potential as a promising therapeutic approach for regulating the microenvironment and alleviating the progression of IDD.

Advancing apoptosis induction in triple negative breast cancer: Empowering treatment with tyrosine-stapled mixed micelles of lapatinib

The available treatment modalities for triple-negative breast cancer (TNBC) face several challenges, including discouraging overall survival outcomes, unavoidable toxicities, and the emergence of drug resistance. Further, there is an amplified requirement for various amino acids to support the uncontrolled proliferation of TNBC. Hence, targeted therapy for enhancing the treatment of TNBC was explored which encompassed hydrophobized (using α-linolenic acid) Pluronic-based mixed micelles having inherent L-type/Large neutral amino acid transporter 1 targeting (tyrosine-stapled) ability (LPT T-MM). LPT T-MM had optimal size (142.34 ± 30.23 nm), polydispersity index (0.224 ± 0.01), and enhanced drug loading capacity (∼10 %). Transmission electron microscopy confirmed their spherical shape. In vitro release studies showed sustained drug release without hemolysis risk. LPT T-MM had higher cellular uptake and cytotoxicity than free LPT. IC50 values for LPT T-MM were significantly reduced in MDA-MB-231 (∼1.64-fold) and 4 T1 (∼1.88-fold) cell lines; apoptosis index was superior in MDA-MB-231 (∼2.04-fold) and 4 T1 cell line (∼2.09-fold) compared to free LPT. LPT T-MM generated more reactive oxygen species and caused mitochondrial membrane depolarization, indicating increased cell death by apoptosis. Thus, LPT T-MM had the ability to promote apoptosis, showed promise in enhancing the payload capabilities and targeting in TNBC.

Unlocking apoptosis in triple negative breast cancer: Harnessing “glutamine trap” to amplify the efficacy of lapatinib-loaded mixed micelles

Certain aggressive cancers, such as triple-negative breast cancer (TNBC), heavily bank on glutamine for their proliferation and survival. In this context, TNBC functions as a “glutamine trap,” extracting circulating glutamine at a rate surpassing that of any other organ. Moreover, the overexpression of Alanine, Serine, Cysteine Transporter 2 (ASCT2), a key player in glutamine uptake, further underscores the significance of targeted therapy to enhance TNBC treatment. This led to the exploration of a novel approach involving hydrophobized Pluronic-based mixed micelles achieved through the use of docosahexaenoic acid and stapled with glutamine for displaying inherent ASCT2 targeting ability—a formulation termed LPT G-MM. LPT G-MM exhibited optimal characteristics, including a size of 163.66 ± 10.34 nm, a polydispersity index of 0.237 ± 0.083, and an enhanced drug loading capacity of approximately 15 %. Transmission electron microscopy validated the spherical shape of these micelles. In vitro release studies demonstrated drug release in a sustained manner without the risk of hemolysis. Importantly, LPT G-MM displayed heightened cellular uptake, increased cytotoxicity, a lower IC50 value, elevated reactive oxygen species, induced mitochondrial membrane depolarization, and a greater apoptosis index in TNBC cell lines compared to free LPT. The pharmacokinetic profile of LPT G-MM revealed a substantial rise in half-life (t1/2) by approximately 1.48-fold and an elevation in the area under the curve [AUC(0→∞)] by approximately 1.19-fold. Moreover, there was a significant reduction in the percentage of tumor volume by approximately 7.26-fold, along with decreased serum toxicity markers compared to free LPT. In summary, LPT G-MM demonstrated promising potential in boosting payload capacities and targeting specificity in the context of TNBC treatment.

Enhancing the drug delivery efficacy of nanodiamond (C20H22): A DFT-based study of doxorubicin and melphalan interaction on pristine and doped surfaces

In this study, density functional theory calculations were conducted to investigate the interaction and electronic properties of two anti-cancer drugs, doxorubicin and melphalan, using pristine and Cr-doped nanodiamonds. The interaction energies of doxorubicin and melphalan onto pristine nanodiamond were calculated to be −259.584 kJ/mol and −251.286 kJ/mol, respectively, indicating an exothermic process. Doping the nanodiamond with Cr enhanced the interaction, with energies of −297.786 kJ/mol for doxorubicin and −286.694 kJ/mol for melphalan. Chemical hardness, highest occupied molecular orbital, and lowest unoccupied molecular orbital analysis showed that both doped complexes with Cr were relatively soft, with nanodiamond-doxorubicin being softer than nanodiamond-melphalan. The high dipole moment of doped nanodiamond-Cr-doxorubicin 9.979 Debye compared to nanodiamond-doxorubicin 3.989 Debye suggests that doped nanodiamond-doxorubicin is more interaction. Thermodynamic calculations revealed the spontaneity and stability of these complexes. Overall, the results demonstrate the enhanced drug loading capacity of Cr-doped nanodiamonds and their potential as drug delivery carriers for doxorubicin and melphalan.

Enhanced drug loading capacity of graphene oxide nanoparticles by polyglycerol hyper branching and increasing the sensitivity of osteosarcoma cancer cells to doxorubicin

Enhanced drug loading capacity of graphene oxide nanoparticles by polyglycerol hyper branching and increasing the sensitivity of osteosarcoma cancer cells to doxorubicin

Design, development, and evaluation of docetaxel-loaded niosomes for the treatment of breast cancer

BackgroundDocetaxel (DTX) has been used to treat numerous types of cancers. Poor solubility, lower bioavailability, and serious side effects limit its use in cancer treatment. The objective of the present research work was to develop DTX-loaded niosomes to overcome these issues and investigate the anticancer effect on breast cancer. Niosomes of DTX were prepared and evaluated to estimate particle size, surface potential, morphology by TEM, %EE, in vitro drug release, %hemolysis, in vitro cytotoxicity, and stability. The cytotoxicity effect of plain DTX and DTX-loaded niosomes was performed on MCF-7 cell lines.ResultsThe mean particle size, zeta potential, and %EE of DTX-loaded niosomes were 244.9 nm, − 7.1 mV, and 97.43%, respectively. Besides, combining the DTX with polymers enhanced drug loading capacity. The TEM images confirmed spherical-shaped niosomes. The IR, DSC, and P-XRD studies indicate no chemical interaction between drug and excipients. The developed DTX niosomes showed a sustained release behavior and lower in vitro cytotoxicity when compared to plain DTX.ConclusionThe current research work demonstrates the suitability of co-loading of DTX in niosomes as a promising approach to enhance the efficiency of DTX.Graphical

Hydrogen Bond-Mediated Supramolecular Polymeric Nanomedicine with pH/Light-Responsive Methotrexate Release and Synergistic Chemo-/Photothermal Therapy.

Complete cancer cure and healing are still difficult, owing to its complexity and heterogeneity. Integration of supramolecular forces, for example, hydrogen bonds (H-bonds), to anti-cancer nanomedicine affords new scaffolds for biomedical material decoration, featuring the advantages of dynamic property and easier processability. Here, we target the construction of H-bond-mediated supramolecular polymer micelles, loaded with a chemotherapeutic drug along with a photothermal agent for synergistic chemo-/photothermal therapies (CT/PTT). To do so, we design and synthesize an amphiphilic ABA-type triblock copolymer, bearing H-bonding moiety (barbiturate, Ba) within the middle hydrophobic B block. The presence of pendant Ba moieties within the hydrophobic core promotes the loading capability of methotrexate (MTX) and transportation stability, benefitting from the formation of specific Ba/MTX H-bonding interactions. IR780, a photothermal agent, concomitantly encapsulated via hydrophobic interactions, facilitates the development of a synergistic CT/PTT modalities, where MTX can be released on demand owing to the dissociation of Ba/MTX H-bonding interactions induced by elevated temperature. Such H-bonding nanomedicine possesses enhanced drug loading capacity and transport performance and can also trigger stimuli-responsive drug release in the tumor zone. We believe that H-bonded nanomedicines provide a fine toolbox that is conducive to attaining biomedical requirements with remarkable values in theranostics that are highly promising in clinical applications.

Development of nanocubosomes co-loaded with dual anticancer agents curcumin and temozolomide for effective colon cancer therapy

Current research aimed to develop nanocubosomes co-loaded with dual anticancer drugs curcumin and temozolomide for effective colon cancer therapy. Drugs co-loaded nanocubosomal dispersion was prepared by modified emulsification method using glyceryl monooleate (GMO), pluronic F127 and bovine serum albumin (BSA) as a lipid phase, surfactant, and stabilizer, respectively. The resulting nanocubosomes were characterized by measuring hydrodynamic particle size, particle size distribution (PSD), drug loading capacity (DL), encapsulation efficiency (EE), colloidal stability and drug release profile. We also physiochemically characterized the nanocubosomes by transmission electron microscopy (TEM), Fourier transform infrared (FTIR), and x-rays diffraction (XRD) for their morphology, polymer drug interaction and its nature, respectively. Further, the in-vitro cell-uptake, mechanism of cell-uptake, in-vitro anti-tumor efficacy and apoptosis level were evaluated using HCT-116 colon cancer cells. The prepared nanocubosomes exhibited a small hydrodynamic particle size (PS of 150 ± 10 nm in diameter) with nearly cubic shape and appropriate polydispersity index (PDI), enhanced drug loading capacity (LC of 6.82 ± 2.03% (Cur) and 9.65 ± 1.53% (TMZ), high entrapment efficiency (EE of 67.43 ± 2.16% (Cur) and 75.55 ± 3.25% (TMZ), pH-triggered drug release profile and higher colloidal stability in various physiological medium. Moreover, the nanocubosomes showed higher cellular uptake, in-vitro cytotoxicity and apoptosis compared to free drugs, curcumin and temozolomide, most likely because its small particle size. In addition, BSA-stabilized nanocubosomes were actively taken by aggressive colon cancer cells that over-expressed the albumin receptors and utilized BSA as nutrient source for their growth. In short, this study provides a new and simple strategy to improve the efficacy and simultaneously overawed the adaptive treatment tolerance in colon cancer.

Evaluation of cephalexin-loaded PHBV nanofibers for MRSA-infected diabetic foot ulcers treatment

The delayed and compromised diabetic foot ulcers (DFUs) healing due to methicillin resistance staphylococcus aureus (MRSA) is an emerging threat to human health and life. Developing new strategies to clear bacteria from ulcerative regions can be helpful to treat DFUs. The current study was designed to fabricate poly (3-hydroxy butyric acid-co-3-hydroxy valeric acid, (PHBV)), nanofibers (PHBV NFs) loaded with cephalexin (CPL) by electrospining technique to improve the bioavailability of CPL at the wound site to inhibit the bacterial growth and trigger the ulcer healing process. Morphological analysis shown that the electrospun nanofibers exhibited smooth surface morphology with an average diameter ranges from 205 ± 25 to 450 ± 55 nm, depending on the cephalexin concentration. The prepared nanofibers showed an enhanced drug loading capacity (LC) and entrapment efficiency (EE) of about 12.1 ± 1.6% and 75.3 ± 2%, respectively. The successful drug loading was also confirmed by FTIR analysis. Moreover, the CPL-loaded PHBV NFs exhibited high water uptake and biodegradation rate compared to blank PHBV NFs. The drug-loaded NFs initially showed a burst drug release followed by a sustained drug release profile with a constant rate up to 48 h. In-vitro studies show that CPL-loaded PHBV NFs exhibited an enhanced antibacterial activity against MRSA strains and have no visible toxic effect against keratinocytes, L929 and HEK293T cell lines. Further, CPL-loaded PHBV NFs showed the enhanced in-vivo bacterial clearance from DFUs using NcZ10 diabetic mice model compared to free CPL. Collectively, our results demonstrated that CPL-loaded PHBV NFs can be applied as a favorable dressing material to treat MRSA-infected chronic DFUs.

Molecular Engineering of Surface Functional Groups Enabling Clinical Translation of Nanoparticle–Drug Conjugates

Antibody–drug conjugates (ADCs) have recently demonstrated impressive successes in targeted drug delivery. Ultrasmall (<10 nm) nanoparticle–drug conjugates (NDCs) share many similarities with ADCs, while their unique physicochemical properties can be further molecularly engineered to overcome the limitations of ADCs presented by tumor heterogeneity. Key challenges in NDC development include linkage chemistry design between nanoparticle carriers and cytotoxic drugs, as well as meeting the stringent criteria for manufacturing controls, stability, and drug release to enable successful clinical translation. Here, we report a robust chemical approach to covalently link both chemotherapeutic drugs and targeting moieties to a poly(ethylene glycol) (PEG)-coated (PEGylated) ultrasmall silica nanoparticle platform via precisely tailoring the particle surface chemistry. This approach employs the interstitial space between PEG chains on the particle surface to load drugs, enabling the significantly enhanced drug loading capacity as compared to ADCs while the favorable biodistribution and pharmacokinetics profiles are maintained. To achieve both high plasma stability and effective drug release in cancer, cyclopentadiene silane molecules are first inserted into the PEG layer of the particles and condensed with silanol groups on the silica core surface. Via the Diels–Alder reaction, the cyclopentadiene groups are then functionalized with groups enabling click chemistry, and cytotoxic payloads are finally clicked onto the particles via cleavable linkers for drug release within the cancer tissue. The targeted NDC resulting from the systematic screening strategy described here has recently advanced to a phase 1/2 human clinical trial.

Brinzolamide-loaded soft contact lens for ophthalmic delivery.

Aim: In this study, brinzolamide (BRZ) was loaded in balafilcon A silicone hydrogel soft contact lens to enhance delivery in glaucoma therapy. Materials & methods: BRZ-loaded soft contact lens was prepared by the soaking method with optimization of pH, temperatureand concentration of drug loading solution. Results: At pH 7.4, loading temperature and concentration of 32°C and 3mg/ml, respectively, enhanced drug loading capacity and release wereobserved. Diffusional experiments showed Higuchi model of release. BRZ loading brought no appreciable changes in the physical properties of soft contact lens, likewise, maintaining stability. Conclusion: The results demonstrated BRZ loading and delivery through silicone hydrogel soft contact lens which provides a potential alternative in glaucoma therapy.

Cytochalasin B Treatment and Osmotic Pressure Enhance the Production of Extracellular Vesicles (EVs) with Improved Drug Loading Capacity.

Extracellular vesicles (EVs) have been highlighted as novel drug carriers due to their unique structural properties and intrinsic features, including high stability, biocompatibility, and cell-targeting properties. Although many efforts have been made to harness these features to develop a clinically effective EV-based therapeutic system, the clinical translation of EV-based nano-drugs is hindered by their low yield and loading capacity. Herein, we present an engineering strategy that enables upscaled EV production with increased loading capacity through the secretion of EVs from cells via cytochalasin-B (CB) treatment and reduction of EV intravesicular contents through hypo-osmotic stimulation. CB (10 µg/mL) promotes cells to extrude EVs, producing ~three-fold more particles than through natural EV secretion. When CB is induced in hypotonic conditions (223 mOsm/kg), the produced EVs (hypo-CIMVs) exhibit ~68% less intravesicular protein, giving 3.4-fold enhanced drug loading capacity compared to naturally secreted EVs. By loading doxorubicin (DOX) into hypo-CIMVs, we found that hypo-CIMVs efficiently deliver their drug cargos to their target and induce up to ~1.5-fold more cell death than the free DOX. Thus, our EV engineering offers the potential for leveraging EVs as an effective drug delivery vehicle for cancer treatment.

Template-free construction of hollow mesoporous Fe3O4 nanospheres as controlled drug delivery with enhanced drug loading capacity

Monodisperse hollow mesoporous Fe3O4 nanospheres have been successfully synthesized via a template-free one-pot solvothermal method under the existence of iron chloride hexahydrate, polyvinylpyrrolidone and urea. A proposed gas-bubble-assisted Ostwald ripening mechanism was allowed to explain the possible fabrication of hollow nanostructures. The formed Fe3O4 nanospheres possessed a narrow particle size distribution with a average hydrodynamic diameter of 392 nm, superparamagnetic characteristics with high saturation magnetization of 74.9 emu/g, as well as the typical mesoporous structures with specific surface area of 27.3 m2/g. Furthermore, it was found that the bare hollow mesoporous Fe3O4 nanospheres showed an insignificant cytotoxicity, but exhibited obvious cytotoxic effects towards HeLa cells after being loaded with the anti-cancer drug of DOX, which could be recommended as a promising and effective drug delivery system with high drug loading capacity and pH-responsive feature. The determined maximum drug loading capacity of DOX on this kind of hollow mesoporous Fe3O4 nanospheres was as high as 0.36 ± 0.04 g/g, which can store and deliver effectively the anticancer drugs to induce death of cancer cells.

Biocompatibility, drug release, and anti‐tumor effect of pH‐sensitive micelles prepared from poly(2‐ethyl‐2‐oxazoline)‐poly(DL‐lactide) block copolymers

AbstractVarious ratios PEOz‐PDLLA diblock copolymers were synthesized through ring‐opening polymerization of DL‐lactide initiated by monohydroxyl terminated poly(2‐ethyl‐2‐oxazoline) (PEOz‐OH). The chemical composition and molar mass of the resulting copolymers were determined by using NMR and GPC. Spherical micelles with a diameter from 104 to 136 nm were obtained via self‐assembly of PEOz‐PDLLA in water, as evidenced by TEM and DLS. The CMC of copolymers was well below 0.01 mg/mL, and showed a decreasing trend with increase of PDLLA block length. A two‐step procedure was applied to encapsulate curcumin taken as a hydrophobic model drug. Copolymers with longer PDLLA block exhibit enhanced drug loading capacity. In vitro drug release was carried out in phosphate buffered saline (PBS) at physiological and slightly acidic pH values. A pH‐sensitive biphasic drug release behavior was detected with an initial burst release followed by slower prolonged release. Lower pH or shorter PDLLA block length leads to higher drug release rate because of faster degradation of micelles. Hemo‐ and cytocompatibility studies illustrated the excellent biocompatibility of PEOz‐PDLLA micelles. MTT assay showed a significant cytotoxicity of curcumin‐loaded micelles against A549 lung cancer cells. Therefore, it can be inferred that PEOz‐PDLLA block copolymers with outstanding biocompatibility, controllable drug loading performance, and prolonged drug release present a good potential as nano‐carrier of hydrophobic drugs.

Nanoemulsions: A Review on the Conceptualization of Treatment for Psoriasis Using a 'Green' Surfactant with Low-Energy Emulsification Method.

Psoriasis is a skin disease that is not lethal and does not spread through bodily contact. However, this seemingly harmless condition can lead to a loss of confidence and social stigmatization due to a persons’ flawed appearance. The conventional methods of psoriasis treatment include taking in systemic drugs to inhibit immunoresponses within the body or applying topical drugs onto the surface of the skin to inhibit cell proliferation. Topical methods are favored as they pose lesser side effects compared to the systemic methods. However, the side effects from systemic drugs and low bioavailability of topical drugs are the limitations to the treatment. The use of nanotechnology in this field has enhanced drug loading capacity and reduced dosage size. In this review, biosurfactants were introduced as a ‘greener’ alternative to their synthetic counterparts. Glycolipid biosurfactants are specifically suited for anti-psoriatic application due to their characteristic skin-enhancing qualities. The selection of a suitable oil phase can also contribute to the anti-psoriatic effect as some oils have skin-healing properties. The review covers the pathogenic pathway of psoriasis, conventional treatments, and prospective ingredients to be used as components in the nanoemulsion formulation. Furthermore, an insight into the state-of-the-art methods used in formulating nanoemulsions and their progression to low-energy methods are also elaborated in detail.

Formulating SLN and NLC as Innovative Drug Delivery Systems for Non-Invasive Routes of Drug Administration.

Colloidal carriers diverge depending on their composition, ability to incorporate drugs and applicability, but the common feature is the small average particle size. Among the carriers with the potential nanostructured drug delivery application there are SLN and NLC. These nanostructured systems consist of complex lipids and highly purified mixtures of glycerides having varying particle size. Also, these systems have shown physical stability, protection capacity of unstable drugs, release control ability, excellent tolerability, possibility of vectorization, and no reported production problems related to large-scale. Several production procedures can be applied to achieve high association efficiency between the bioactive and the carrier, depending on the physicochemical properties of both, as well as on the production procedure applied. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes Lipid-based nanocarriers (LNCs) versatile delivery system for various routes of administration. The route of administration has a significant impact on the therapeutic outcome of a drug. Thus, the non-invasive routes, which were of minor importance as parts of drug delivery in the past, have assumed added importance drugs, proteins, peptides and biopharmaceuticals drug delivery and these include nasal, buccal, vaginal and transdermal routes. The objective of this paper is to present the state of the art concerning the application of the lipid nanocarriers designated for non-invasive routes of administration. In this manner, this review presents an innovative technological platform to develop nanostructured delivery systems with great versatility of application in non-invasive routes of administration and targeting drug release.

Engineering MIL-100(Fe) on 3D porous natural diatoms as a versatile high performing platform for controlled isoniazid drug release, Fenton’s catalysis for malachite green dye degradation and environmental adsorbents for Pb2+ removal and dyes

Metal-organic frameworks (MOFs) emerged as one of the promising functional materials for broad applications. To improve the sustainability of their synthetic route and extend their applications are still demanding and challenging task. Herein, to address this problem, we report practical use of “eco-friendly” approach to create new type of hybrid materials by combining MOFs with naturally available hierarchical diatom biosilica (DE) acts as 3D porous scaffolds. This combination of high surface area, an unique 3D diatom architecture with 2D MOFs structure with specific chemical functionalities –OH, –COOH and Fe atoms confined in MIL-100(Fe)-DE hybrid materials and explored for a wide range of applications like drug delivery, catalyst support and environmental adsorbents. To prove drug delivery application for MIL-100(Fe)-DE, isoniazid (INH) anti-TBC (tuberculosis) drug is selected as typical drug model showing an enhanced drug loading capacity of 9.6 ± 1.6% and an extended in vitro controlled drug release performances over 23 days. This is significant improvement of short drug release characterstics and biological half life of INH (1–4 h) that limits to rich full therapeutic benefits for treatment of TBC. A heterogeneous Fenton’s catalysis study of MIL-100(Fe)-DE showed a rapid degradation of Malachite green (MG) dye within 60 min with degradation efficiency of 99.02 ± 1.3%. To prove environment remediation performances at 25 °C and in pH 6, MIL-100(Fe)-DE displayed efficient removal of Pb2+ with removal efficiency of 96.45 ± 2.1%, high adsorption capacity of 155 mg/g and the improved partition co-efficient (PC) was 87.32 mg.g−1.µM−1 for Pb2+ of (50 mg/L) with excellent reusability. Finally, MIL-100(Fe)-DE hybrid was tested for the removal of cationic dyes such as methylene blue (MB), rhodamine B (RhB) and anionic dyes like congo red (CR) and erichrome black T (EBT) showing 96.10 ± 1.3, 75.11 ± 1.95, 98.11 ± 1.7 and 76 ± 1.88% of removal efficiency respectively.

Structural Modification of Nanomicelles through Phosphatidylcholine: The Enhanced Drug-Loading Capacity and Anticancer Activity of Celecoxib-Casein Nanoparticles for the Intravenous Delivery of Celecoxib.

This study aims to stabilize loaded celecoxib (CX) by modifying the structure of casein nanoparticles through phosphatidylcholine. The results show that Egg yolk phosphatidylcholine PC98T (PC) significantly increased the stability of CX-PC-casein nanoparticles (NPs) (192.6 nm) from 5 min (CX-β-casein-NPs) to 2.5 h at 37 °C. In addition, the resuspended freeze-dried NPs (202.4 nm) remained stable for 2.5 h. Scanning electron microscopy indicated that PC may block the micropore structures in nanoparticles by ultrasonic treatment and hence improve the physicochemical stability of CX-PC-casein-NPs. The stability of the NPs was positively correlated with their inhibiting ability for human malignant melanoma A375 cells. The structural modification of CX-PC-casein-NPs resulted in an increased intracellular uptake of CX by 2.4 times than that of the unmodified ones. The pharmacokinetic study showed that the Area Under Curve (AUC) of the CX-PC-casein-NPs was 2.9-fold higher in rats than that of the original casein nanoparticles. When CX-PC-casein-NPs were intravenously administrated to mice implanted with A375 tumors (CX dose = 16 mg/kg bodyweight), the tumor inhibition rate reached 56.2%, which was comparable to that of paclitaxel (57.3%) at a dose of 4 mg/kg bodyweight. Our results confirm that the structural modification of CX-PC-casein-NPs can effectively prolong the remaining time of specific drugs, and may provide a potential strategy for cancer treatment.

Novel application of mixed solvency concept in the development of oral liquisolid system of a poorly soluble drug, cefixime and its evaluation

Application of mixed solvency has been employed in the present research work to develop a liquisolid system (Powder formulation) of poorly water soluble drug, cefixime (as model drug). Material and Methods: For poorly water soluble drug cefixime, combination of solubilizers such as sodium acetate, sodium caprylate and propylene glycol as mixed solvent systems were used to decrease the overall concentration of solubilizers required to produce substantial increase in solubility and thereby resulting in enhanced drug loading capacity of cefixime. The procured sample of cefixime was characterized by melting point, IR, UV and DSC studies. Stability studies of liquisolid system of cefixime were performed for two months at room temperature, 30˚C and 40˚C. All the formulations were physically, chemically, and microbiologically stable. Conclusion: Mixed solvency concept has been successfully employed for enhancing the drug loading of poorly water soluble drug, cefixime.&#x0D; Keywords: Solubility, cefixime, liquisolid system, mixed solvency concept.