ABSTRACT
Pluronic F-127 based dual-responsive (pH/temperature) hydrogel drug delivery system was developed involving polysaccharide-based nano-conjugate of hyaluronic acid and chitosan oligosaccharide lactate and applied for loading of gallic acid which is the principal component of traditional Chinese medicine Cortex Moutan recommended in the treatment of atopic dermatitis. The polysaccharide-based nano-conjugate was used as pH-responsive compound in the formulation and its amphiphilic character was determined colorimetrically. Microstructure analysis by SEM and TEM indicated highly porous hydrogel network and well-dispersed micellar structures, respectively, after modification with the nano-conjugate, and so, release property of the hydrogel for drug was significantly improved. Different pH-conditions were applied here to see pH-responsiveness of the formulation and increase in acidity of external environment gradually diminished mechanical stability of the hydrogel and that was reflected on the drug release property. Rheology was performed to observe sol-gel transition of the formulation and showed better rheological properties after modification with nano-conjugate. In this study, the cytotoxicity results of PF127 based formulations loaded with/without gallic acid showed cell viability of > 80.0 % for human HaCaT keratinocytes in the concentration range of 0.0-20.0 µg/ml.
Subject(s)
Chitin/analogs & derivatives , Hyaluronic Acid/chemistry , Hydrogels/chemistry , Nanoconjugates/chemistry , Cell Line , Cell Survival/drug effects , Chitin/chemistry , Chitin/toxicity , Chitosan , Drug Liberation , Gallic Acid/chemistry , Humans , Hyaluronic Acid/toxicity , Hydrogels/chemical synthesis , Hydrogels/toxicity , Hydrogen-Ion Concentration , Nanoconjugates/toxicity , OligosaccharidesABSTRACT
Multifunctional nanoconjugates possessing an assortment of key functionalities such as magnetism, florescence, cell-targeting, pH and thermo-responsive features were developed for dual drug delivery. The novelty lies in careful conjugation of each of the functionality with magnetic Fe3O4 nanoparticles by virtue of urethane linkages instead of silica in a simple one pot synthesis. Further ß-cyclodextrin (CD) was utilized to carry hydrophobic as well as hydrophilic drug. Superlative release of DOX could be obtained under acidic pH conditions and elevated temperature, which coincides with the tumor microenvironment. Mathematical modelling studies revealed that the drug release kinetics followed diffusion mechanism for both hydrophobic drug and hydrophilic drug. A number of fluorophores onto a single nanoparticle produced a strong fluorescence signal to optically track the nanoconjugates. Enhanced internalization due to folate specificity could be observed by fluorescence imaging. Further their accumulation driven by magnet near tumor site led to magnetic hyperthermia. in vitro studies confirmed the nontoxicity and hemocompatibility of the nanoconjugates. Remarkable cell death was observed with drug-loaded nanoconjugates at very low concentrations in cancer cells. The internalization and cellular uptake of poor bioavailable anticancer agent curcumin were found to be remarkably enhanced on dosing the drug loaded nanoconjugates as compared to free curcumin. Site specific drug delivery due to folate conjugation and subsequent significant suppression in tumor growth was demonstrated by in vivo studies.
Subject(s)
Antineoplastic Agents/therapeutic use , Drug Carriers/chemistry , Nanoconjugates/chemistry , Theranostic Nanomedicine/methods , beta-Cyclodextrins/chemistry , Animals , Carcinoma, Hepatocellular/drug therapy , Curcumin/chemistry , Curcumin/therapeutic use , Doxorubicin/chemistry , Doxorubicin/therapeutic use , Drug Carriers/chemical synthesis , Drug Carriers/toxicity , Drug Liberation , Female , Fluoresceins/chemical synthesis , Fluoresceins/chemistry , Fluoresceins/toxicity , Fluorescence , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/chemistry , Fluorescent Dyes/toxicity , HeLa Cells , Humans , Magnetite Nanoparticles/chemistry , Magnetite Nanoparticles/toxicity , Male , Mice, Inbred BALB C , Nanoconjugates/toxicity , beta-Cyclodextrins/chemical synthesis , beta-Cyclodextrins/toxicityABSTRACT
Gold nanoparticles (GNPs) are synthesized using the medicinal plant Leucas Aspera extract (LAE) and poly lactic acid-co-poly ethylene glycol-co-poly lactic acid (PLA-PEG-PLA) copolymer by water-in-oil (W/O) emulsion method. The proposed method of W/O emulsion technique involves synthesis of GNPs and loading of Leucas Aspera extract on to the PLA-PEG-PLA copolymer matrix simultaneously. The synthesized GNPs are characterized by Fourier transform infra-red (FTIR) spectroscopy, dynamic light scattering (DLS), X-ray diffractometry (XRD) and transmission electron microscopy (TEM). The GNPs-LAE loaded polymer NPs are examined for the in vitro cytotoxicity on South African green monkey's kidney cells. The GNPs-LAE loaded polymer nanoconjugates exhibit maximum up to 95% of cell viability with 100 µg concentration of GNPs in the sample. The GNPs-LAE loaded polymer NPs exhibit better anti-inflammatory activity when compared to the pure LAE.
Subject(s)
Blood/immunology , Drugs, Chinese Herbal/chemistry , Gold/toxicity , Lactates/chemistry , Metal Nanoparticles/toxicity , Nanoconjugates/toxicity , Polyethylene Glycols/chemistry , Absorption, Physicochemical , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/chemical synthesis , Blood/drug effects , Chlorocebus aethiops , Diffusion , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/toxicity , Gold/administration & dosage , Metal Nanoparticles/administration & dosage , Nanocapsules , Nanoconjugates/administration & dosage , Nanoconjugates/chemistry , Surface-Active Agents/chemistry , Vero CellsABSTRACT
Near-infrared dyes can be used as theranostic agents in cancer management, based on their optical imaging and localized hyperthermia capabilities. However, their clinical translatability is limited by issues such as photobleaching, short circulation times, and nonspecific biodistribution. Nanoconjugate formulations of cyanine dyes, such as IR820, may be able to overcome some of these limitations. We covalently conjugated IR820 with 6 kDa polyethylene glycol (PEG)-diamine to create a nanoconjugate (IRPDcov) with potential for in vivo applications. The conjugation process resulted in nearly spherical, uniformly distributed nanoparticles of approximately 150 nm diameter and zeta potential -0.4±0.3 mV. The IRPDcov formulation retained the ability to fluoresce and to cause hyperthermia-mediated cell-growth inhibition, with enhanced internalization and significantly enhanced cytotoxic hyperthermia effects in cancer cells compared with free dye. Additionally, IRPDcov demonstrated a significantly longer (P<0.05) plasma half-life, elimination half-life, and area under the curve (AUC) value compared with IR820, indicating larger overall exposure to the theranostic agent in mice. The IRPDcov conjugate had different organ localization than did free IR820, with potential reduced accumulation in the kidneys and significantly lower (P<0.05) accumulation in the lungs. Some potential advantages of IR820-PEG-diamine nanoconjugates may include passive targeting of tumor tissue through the enhanced permeability and retention effect, prolonged circulation times resulting in increased windows for combined diagnosis and therapy, and further opportunities for functionalization, targeting, and customization. The conjugation of PEG-diamine with a near-infrared dye provides a multifunctional delivery vector whose localization can be monitored with noninvasive techniques and that may also serve for guided hyperthermia cancer treatments.
Subject(s)
Antineoplastic Agents/chemistry , Diamines/chemistry , Indocyanine Green/analogs & derivatives , Nanoconjugates/chemistry , Optical Imaging/methods , Polyethylene Glycols/chemistry , Algorithms , Animals , Antineoplastic Agents/pharmacokinetics , Cell Line, Tumor , Cell Proliferation/drug effects , Diamines/toxicity , Humans , Hyperthermia, Induced , Indocyanine Green/chemistry , Indocyanine Green/pharmacokinetics , Indocyanine Green/toxicity , Mice , Nanoconjugates/toxicity , Nanotechnology , Polyethylene Glycols/toxicity , Surgery, Computer-Assisted , Tissue DistributionABSTRACT
Hyaluronan-cisplatin conjugate nanoparticles (HCNPs) were chosen as colon-targeting drug-delivery carriers due to the observation that a variety of malignant tumors overexpress hyaluronan receptors. HCNPs were prepared by mixing cisplatin with a hyaluronan solution, followed by dialysis to remove trace elements. The cells treated with HCNPs showed significantly lower viability than those treated with cisplatin alone. HCNPs were entrapped in Eudragit S100-coated pectinate/alginate microbeads (PAMs) by using an electrospray method and a polyelectrolyte multilayer-coating technique in aqueous solution. The release profile of HCNPs from Eudragit S100-coated HCNP-PAMs was pH-dependent. The percentage of 24-hour drug release was approximately 25.1% and 39.7% in pH 1.2 and pH 4.5 media, respectively. However, the percentage of drug released quickly rose to 75.6% at pH 7.4. Moreover, the result of an in vivo nephrotoxicity study demonstrated that Eudragit S100-coated HCNP-PAMs treatment could mitigate the nephrotoxicity that resulted from cisplatin. From these results, it can be concluded that Eudragit S100-coated HCNP-PAMs are promising carriers for colon-specific drug delivery.