Drug Release Profiles of Mitomycin C Encapsulated Quantum Dots–Chitosan Nanocarrier System for the Possible Treatment of Non-Muscle Invasive Bladder Cancer

Nanotechnology-based drug delivery systems are an emerging technology for the targeted delivery of chemotherapeutic agents in cancer therapy with low/no toxicity to the non-cancer cells. With that view, the present work reports the synthesis, characterization, and testing of Mn:ZnS quantum dots (QDs) conjugated chitosan (CS)-based nanocarrier system encapsulated with Mitomycin C (MMC) drug. This fabricated nanocarrier, MMC@CS-Mn:ZnS, has been tested thoroughly for the drug loading capacity, drug encapsulation efficiency, and release properties at a fixed wavelength (358 nm) using a UV–Vis spectrophotometer. Followed by the physicochemical characterization, the cumulative drug release profiling data of MMC@CS-Mn:ZnS nanocarrier (at pH of 6.5, 6.8, 7.2, and 7.5) were investigated to have the highest release of 56.48% at pH 6.8, followed by 50.22%, 30.88%, and 10.75% at pH 7.2, 6.5, and 7.5, respectively. Additionally, the drug release studies were fitted to five different pharmacokinetic models including pesudo-first-order, pseudo-second-order, Higuchi, Hixson–Crowell, and Korsmeyers–Peppas models. From the analysis, the cumulative MMC release suits the Higuchi model well, revealing the diffusion-controlled mechanism involving the correlation of cumulative drug release proportional to the function square root of time at equilibrium, with the correlation coefficient values (R2) of 0.9849, 0.9604, 0.9783, and 0.7989 for drug release at pH 6.5, 6.8, 7.2, and 7.5, respectively. Based on the overall results analysis, the formulated nanocarrier system of MMC synergistically envisages the efficient delivery of chemotherapeutic agents to the target cancerous sites, able to sustain it for a longer time, etc. Consequently, the developed nanocarrier system has the capacity to improve the drug loading efficacy in combating the reoccurrence and progression of cancer in non-muscle invasive bladder diseases.

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Nanomaterials for Targeted Delivery of Anticancer Drugs: An Overview

Current Nanomaterials ◽

10.2174/2405461506666210119095130 ◽

2021 ◽

Vol 06 ◽

Author(s):

Bhavna Choudhary ◽

Pubalee Sarmah

Keyword(s):

Drug Delivery ◽

Targeted Delivery ◽

Chemotherapeutic Agents ◽

Cancer Drug ◽

Cancer Treatments ◽

Area Of Interest ◽

Efficient Delivery ◽

Delivery Vehicles ◽

Materials Used ◽

Developing Area

: Application of nanomaterials in drug delivery is a rapidly developing area of interest. The main intention in the development of these drug delivery vehicles is to successfully know the targeted delivery-related efforts and carrying drugs to the required sites of therapeutic action with reduction in adverse side effects. The task for targeted drug delivery to reach pathological are-as has increased advances in nanomedicine. But the high toxicity of uncoated nanoparticles restricts the use in humans. So, to reduce toxicity, the encapsulation of nanoparticles is done with bio compatible materials. There are many efficient delivery systems thathave been developed in which nanoparticles are loaded with the cancer drug involvingbi-layer molecules. The ﬁelds of nanotechnology has always played a crucial role in electronics, biology and medicine. Its application can be ap-praised, as it involves the materials to be designed at atomic and molecular level.This article reviews different types of nano- materials used as delivery vehicles for chemotherapeutic agents and their mechanism of action that improve the therapeutic efficacy of the drugs. The recent scientiﬁc advances in the area of chemotherapy are also discussed with emphasizingthe fu-ture prospects in cancer treatments.

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Synthesis, Characterization and Safety Profiling of Eudragit-Based pHResponsive Hydrogels: A Promising Platform for Colonic Delivery of Losartan Potassium

Current Drug Delivery ◽

10.2174/1567201816666190208165511 ◽

2019 ◽

Vol 16 (6) ◽

pp. 548-564

Author(s):

Shabina Mahmood ◽

Manal Ali Buabeid ◽

Kaleem Ullah ◽

Ghulam Murtaza ◽

Abdul Mannan ◽

...

Keyword(s):

Drug Release ◽

Acrylic Acid ◽

Drug Loading ◽

Control Group ◽

Colonic Delivery ◽

Hydrophilic Drugs ◽

Promising Tool ◽

Inverse Results ◽

Efficient Delivery ◽

Prolonged Drug Release

Objective: The aim of the present study was to design an efficient delivery system with an anticipated swelling and drug release properties for a prolonged drug release as well as to target colon for various hydrophilic drugs. Methods: For this purpose, the pH-responsive hydrogel comprising a combination of Eudragit and acrylic acid was formed. The hydrogels were characterized for spectral (FTIR), thermal (TGA/DSC), structural (XRD), and morphological (SEM) investigations. Oral tolerability was assessed in rabbits for biocompatibility and oral use of the prepared hydrogels. Results: The results showed that an increased incorporation of Eudragit and cross-linking agent retorted the swelling, drug loading, and drug release properties at both acid (pH 1.2) and basic pH (pH 6.8 and 7.4) , while acrylic acid presented the inverse results. The oral tolerability and toxicity studies depicted that the developed hydrogels were safe up to 3800 mg/kg body weight and caused no hematological or histopathological changes when compared with the control group. Conclusion: Therefore, the newly developed formulations presented adequate swelling, drug loading, release behavior, and biocompatibility properties and thus can be used as a promising tool for the colonic delivery of various hydrophilic drugs.

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Transferrin/α-tocopherol modified poly(amidoamine) dendrimers for improved tumor targeting and anticancer activity of paclitaxel

Nanomedicine ◽

10.2217/nnm-2019-0128 ◽

2019 ◽

Vol 14 (24) ◽

pp. 3159-3176

Author(s):

Himanshu Bhatt ◽

Sri Vishnu Kiran Rompicharla ◽

Balaram Ghosh ◽

Vladimir Torchilin ◽

Swati Biswas

Keyword(s):

Epithelial Cells ◽

Cellular Uptake ◽

Delivery System ◽

Targeted Delivery ◽

Chemotherapeutic Agents ◽

Efficient Delivery ◽

Tocopheryl Succinate ◽

Cervical Epithelial Cells ◽

Poly Ethylene ◽

3D Spheroids

Aim: Transferrin anchored, poly(ethylene glycol) (PEG) and α-tocopheryl succinate (α-TOS) conjugated generation 4 dendrimer has been prepared in order to develop a tumor targeted delivery system of a hydrophobic chemotherapeutic agent, paclitaxel (PTX). Materials & methods: The dendrimers were characterized physicochemically for size, ζ and encapsulation ability. The cellular uptake, cytotoxicity potential and apoptosis of prepared nanoconstruct were evaluated in human cervical epithelial cells monolayer and 3D spheroids. Results & conclusion: G4-TOS-PEG-Tf demonstrated increased cellular uptake, cytotoxicity and apoptotic potential of PTX compared with free PTX and G4-TOS-PEG-PTX. G4-TOS-PEG-Tf-PTX inhibited growth of human cervical epithelial cells spheroids significantly. The newly developed dendrimers hold promise as an efficient delivery system for PTX or other hydrophobic chemotherapeutic agents for targeted delivery to tumors.

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Targeted Delivery of Methotrexate through pH-sensitive Hydrogel: To Treat Colon Pathology

10.20944/preprints202009.0510.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Muhammad Akhlaq ◽

Inam Ullah ◽

Asif Nawaz ◽

Muhammad Safdar ◽

Abul Kalam Azad ◽

...

Keyword(s):

Drug Release ◽

Targeted Delivery ◽

Phosphate Buffer ◽

Drug Loading ◽

Research Work ◽

Fickian Diffusion ◽

Diffusion Method ◽

Gravimetric Analysis ◽

Order Kinetic ◽

Pva Hydrogel

The purpose of current research work was to formulate and typify gelatin and poly(vinyl) alcohol (Gel/PVA) hydrogel which would be highly pH-responsive and can able to accomplish targeted delivery of methotrexate in order to treat the colo-rectal pathologies. The primed gel/pva hydrogel discs were subjected to various physicochemical techniques i.e. swelling, diffusion co-efficient, sol-gel analysis and porosity using three altered sorts of pH (1.2, 6.8 & 7.4) phosphate buffer solutions for assessment/evaluation, and their characterization was done through Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analysis (TGA). Shape alteration and controlled methotrexate of release of Gel/PVA hydrogel have been done using three type of pH (1.2, 6.8 & 7.4) phosphate buffer mediums. Methotrexate was loaded through in-situ drug loading method due to hydrophobicity. Different kinetic models (first order & zero order kinetic), Higuchi model and Krosmere peppas model/Power law were applied to manipulate the drug release data. Physicochemical evaluation tests and drug release profile results were found insignificant (p< 0.05) in various pH mediums and dependent upon polymers concentration pH of medium and cross-linker amount. Kinetic model disclosed that release of methotrexate from Gel/PVA hydrogel follow non-Fickian diffusion method. It became concluded from this research work that release of methotrexate Gel/PVA hydrogel in targeted colon area can be achieved for treating colo-rectal disorders.

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Bioavailability Enhancement of Vitamin E TPGS Coated Liposomes of Nintedanib Esylate Formulation Developed Using Quality by Design Approach

10.21203/rs.3.rs-1134521/v1 ◽

2022 ◽

Author(s):

Shabari Girinath Kala ◽

Santhivardhan Chinni

Keyword(s):

Drug Release ◽

Oral Bioavailability ◽

High Speed ◽

Drug Loading ◽

Physicochemical Characterization ◽

Amorphous State ◽

Male Rats ◽

Molar Ratio ◽

Pharmacokinetic Data

Abstract PurposeNintedanib esylate (NE) is a kinase inhibitor designated for the cure of non-small cell lung cancer suffers from first-pass metabolism which resulted in low oral bioavailability (~4.7%). The intent of this exploration was to increase the oral bioavailability of NE by means of TPGS coated liposomes. MethodsThe NE-loaded TPGS coated liposomes were formulated by high-speed homogenization by optimizing process parameters like phospholipids: cholesterol molar ratio, drug loading and sonication time through the design of experiments. The drug's behaviour was studied using a variety of techniques, including physicochemical characterization, in-vitro and in-vivo studies. ResultsThe NE-liposomes had a particle size of 125±6.68 nm, entrapment efficiency of 88.64±4.12% and zeta potential of +46±2.75 mV. X-ray diffraction analysis revealed that NE had been converted to an amorphous state, while transmission electron microscope images showed spherical shape and smooth coating of TPGS on surface of liposomes. The formulation showed Higuchi kinetics with sustained drug release of 88.72 ± 3.40% in 24 hours. Cellular uptake of C-6 labelled liposomes was observed in A-549 cells and cytotoxicity testing revealed that NE-liposomes were more effective than marketed formulation Ofev®. Formulation remained in simulated fluids and for three months in stability chamber and. Liposomal oral bioavailability was ~6.23 times greater in sprague dawley male rats compared to marketed formulation Ofev®, according to in-vivo pharmacokinetic data. ConclusionNE-Liposomal formulations are better for oral administration compared to the marketed capsules because of the prolonged drug release and increased oral bioavailability as a result, the developed formulation can become a successful strategy in cancer chemotherapy.

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Design, Formulation and Characterization of Microspheres containing Mesalamine for the Treatment of Ulcerative Colitis

Research Journal of Science and Technology ◽

10.52711/2349-2988.2021.00025 ◽

2021 ◽

pp. 165-169

Author(s):

Deepak Patel ◽

Sunil Kumar Shah ◽

Chandra Kishore Tyagi

Keyword(s):

Ulcerative Colitis ◽

Drug Release ◽

Targeted Delivery ◽

Drug Loading ◽

Polymer Concentration ◽

Entrapment Efficiency ◽

Simulated Gastric Fluid ◽

Simulated Intestinal Fluid ◽

Chitosan Microspheres ◽

Increase With Increase

The purpose of the present study was to prepare, characterize and evaluate the colon-targeted microspheres of mesalamine for the treatment and management of ulcerative colitis (UC). Microspheres were prepared by the ionic-gelation emulsification method using tripolyphosphate (TPP) as cross linking agent. The microspheres were coated with Eudragit S-100 by the solvent evaporation technique to prevent drug release in the stomach. The prepared microspheres were evaluated for surface morphology, entrapment efficiency, drug loading, micromeritic properties and in-vitro drug release. The microspheres formed had rough surface as observed in scanning electron microscopy. The entrapment efficiency of microspheres ranged from 43.72% - 82.27%, drug loading from 20.28% - 33.26%. The size of the prepared microspheres ranged between 61.22-90.41μm which was found to increase with increase in polymer concentration. All values are statistically significant as p<0.05. The release profile of mesalamine from eudragit-coated chitosan micro-spheres was found to be pH dependent. It was observed that Eudragit S100 coated chitosan microspheres gave no release in the simulated gastric fluid, negligible release in the simulated intestinal fluid and maximum release in the colonic environment. It was concluded from the study that Eudragit-coated chitosan microspheres were promising carriers for colon-targeted delivery of Mesalamine.

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Polymer-Lipid Hybrid Nanoparticles: A Next-Generation Nanocarrier for Targeted Treatment of Solid Tumors

Current Pharmaceutical Design ◽

10.2174/1381612826666200116150426 ◽

2020 ◽

Vol 26 (11) ◽

pp. 1206-1215 ◽

Cited By ~ 9

Author(s):

Md. Rizwanullah ◽

Meraj Alam ◽

Harshita ◽

Showkat R. Mir ◽

Mohd. M.A. Rizvi ◽

...

Keyword(s):

Drug Release ◽

Solid Tumors ◽

Targeted Delivery ◽

Therapeutic Potential ◽

Drug Loading ◽

Building Blocks ◽

Targeted Treatment ◽

Hybrid Nanoparticles ◽

Hybrid Architecture ◽

Chemotherapeutic Drugs

: At present, cancer is the most deadly disease and one of the most common causes of death worldwide providing different obstacles to chemotherapy including non-specific biodistribution of chemotherapeutic drugs, dose-related adverse effects, development of metastasis and chemoresistance. Nanoparticle-based targeted delivery of chemotherapeutics gained enormous attention in the treatment of solid tumors as they provide many significant advantages including prolonged drug release, enhanced systemic half-life, decreased toxicity and targeted drug delivery. Polymer–lipid hybrid nanoparticles (PLHNPs) are the most effective nanoplatform that develop from building blocks of polymers and lipids. PLHNPs combine the unique advantages of both lipid-based nanoparticles as well as polymeric nanoparticles. PLHNPs integrate biocompatible polymers and biomimetic lipids in their architecture, which imparts PLHNPs with wide versatility for delivering chemotherapeutic drugs of different physicochemical characteristics to their target site of action. The hybrid architecture of PLHNPs provides many exceptional advantages such as small particle size, encapsulation of more than one anticancer drugs, high drug loading capacity and modified drug release profile. Furthermore, the surface decoration of PLHNPs improves the therapeutic potential of the chemotherapeutic drug by selective targeting of tumor tissue and reduces the side effects by decreasing non-specific biodistribution. This review highlights the challenges in the treatment of solid tumors by using nanoparticles system, rationale and targeting strategies of PLHNPs in the targeted treatment of solid tumors, and current progress of PLHNPs in the management of different types of solid tumors.

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Enhanced intracellular delivery of Curcumin by Chitosan-Lipoic acid as reduction-responsive nanoparticles

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021999200727153513 ◽

2020 ◽

Vol 21 ◽

Author(s):

Somayeh Rezaei ◽

Soheila Kashanian ◽

Yadollah Bahrami ◽

Hossein Zhaleh ◽

Luis J. Cruz

Keyword(s):

Drug Release ◽

Lipoic Acid ◽

Anticancer Agents ◽

Drug Loading ◽

Normal Tissues ◽

Efficient Delivery ◽

Mean Size ◽

Anti Tumor Activity ◽

Assay Detection

Aim: Enhancement of anti-tumor activity of the chemotherapeutic agent CUR by redox-sensitive nanoparticle to get a deeper in-sight into cancer therapy. Background: Tumor targetability and stimulus are widely used to study the delivery of drugs for cancer diagnosis and treatment because poor cellular uptake and inadequate intracellular drug release lead to inefficient delivery of anticancer agents to tumor tissue. Objective: Studies distinguishing between tumor and normal tissues or redox-sensitive systems is using glutathione (GSH) as a significant signal. Methods: In this study, we designed Chitosan-Lipoic acid Nanoparticles (CS-LANPs) to improve drug delivery for breast cancer treatmentby efficient delivery of Curcumin (CUR). The properties of blank CS-LANPs were studied in detail. The size and the polydispersity index (PDI) of the CS-LANPs were optimized. Results: The results indicate the mean size and PDI of the blank CS-LANPs were around 249 nm and 0.125, respectively. However, the drug loading (DL) and encapsulation efficiency (EE) of the CS-LANPs were estimated to be about 18.22% and 99.80%, respectively. Com-pared to non-reductive conditions, the size of reduction-sensitive CS-LANPs increased significantly under reductive conditions. Therefore, the drug release of CS-LANPs in the presence of glutathione was much faster than that of non-GSH conditions .Moreover, the antitumor ef-fect of CS-LANPs on MCF-7 cells was determined in vitro by MTT assay, cell cytotoxicity, Caspase-3 Assay, detection of mitochondrial membrane potential and quantification of apoptosis incidence. Conclusion: CS-LANPs showed a remarkably increased accumulation in tumor cells and had a better tumor inhibitory activity in vitro. CS-LANPs could successfully deliver drugs to cancer cells and revealed better efficiency than free CUR.

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Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery

Medicines ◽

10.3390/medicines4040087 ◽

2017 ◽

Vol 4 (4) ◽

pp. 87 ◽

Cited By ~ 4

Author(s):

Francesco Petrella ◽

Isabella Rimoldi ◽

Stefania Rizzo ◽

Lorenzo Spaggiari

Keyword(s):

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Targeted Delivery ◽

Drug Loading ◽

Tumour Microenvironment ◽

Chemotherapeutic Agents ◽

Immunomodulatory Activity ◽

Neoplastic Cells

Mesenchymal stromal cells are a population of undifferentiated multipotent adult cells possessing extensive self-renewal properties and the potential to differentiate into a variety of mesenchymal lineage cells. They express broad anti-inflammatory and immunomodulatory activity on the immune system and after transplantation can interact with the surrounding microenvironment, promoting tissue healing and regeneration. For this reason, mesenchymal stromal cells have been widely used in regenerative medicine, both in preclinical and clinical settings. Another clinical application of mesenchymal stromal cells is the targeted delivery of chemotherapeutic agents to neoplastic cells, maximizing the cytotoxic activity against cancer cells and minimizing collateral damage to non-neoplastic tissues. Mesenchymal stem cells are home to the stroma of several primary and metastatic neoplasms and hence can be used as vectors for targeted delivery of antineoplastic drugs to the tumour microenvironment, thereby reducing systemic toxicity and maximizing antitumour effects. Paclitaxel and gemcitabine are the chemotherapeutic drugs best loaded by mesenchymal stromal cells and delivered to neoplastic cells, whereas other agents, like pemetrexed, are not internalized by mesenchymal stromal cells and therefore are not suitable for advanced antineoplastic therapy. This review focuses on the state of the art of advanced antineoplastic cell therapy and its future perspectives, emphasizing in vitro and in vivo preclinical results and future clinical applications.

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Contemporary Intravesical Treatment Options for Urothelial Carcinoma of the Bladder

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2006.0086 ◽

2006 ◽

Vol 4 (10) ◽

pp. 1027-1036 ◽

Cited By ~ 18

Author(s):

Stephen A. Brassell ◽

Ashish M. Kamat

Keyword(s):

Mitomycin C ◽

Treatment Options ◽

Chemotherapeutic Agents ◽

Systemic Absorption ◽

Interferon Α ◽

Maintenance Schedule ◽

Intravesical Treatment ◽

Carcinoma Of The Bladder ◽

Muscle Invasive ◽

Ideal Method

To provide a comprehensive review of intravesical treatment options for non–muscle-invasive bladder cancer, we performed a search of the PubMed database for articles between 1980 and 2006 that reported on intravesical agents for treating this disease. Data were compiled and analyzed, emphasizing findings from large multicenter trials, studies providing reproducible results, data that could be confirmed by cross-referencing the literature, and phase I or II studies for pertinent novel agents. A critical analysis of evidence shows that: 1) treatment with Bacillus Calmette-Guérin (BCG), including a maintenance schedule (with or without interferon-α), is the most effective therapy for limiting recurrence, is the only therapy that reduces the incidence of progression, and overall is superior to chemotherapy; 2) mitomycin C, gemcitabine, anthracyclines, and thiotepa provide similar benefits for preventing recurrence in patients with minimal effect on progression; and 3) using chemotherapeutic agents immediately after transurethral resection (when use of BCG is contraindicated because of the risk for systemic absorption) reduces the recurrence rate by up to 50% and seems to be the ideal method of chemotherapy. Although various clinical factors dictate which agent is most appropriate for an individual patient, the current literature supports a single perioperative dose of intravesical mitomycin C followed, in appropriate cases, by induction and maintenance therapy with intravesical BCG.

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