An enzyme-mediated in situ hydrogel based on polyaspartamide derivatives for localized drug delivery and 3D scaffolds

As a widely used anticancer drug, doxorubicin (DOX) could induce cell death mainly via interfering with DNA activity; thus, DOX could perform therapeutic effects mainly in the cell nucleus. However, most of the reported drug delivery systems lacked the well localization in the nucleus and released DOX molecules into the cytoplasm. Due to formidable barriers formed in the nuclear envelope, only around 1% of DOX could reach the nucleus and keep active. Therefore, DOX molecules were inevitably overloaded to achieve the desired therapeutic efficacy, which would induce serious side effects. Herein, we developed a highly localized drug nanocarrier for in situ release of DOX molecules to their action site where they could directly interfere with the DNA activity. In this work, we used cationic polymer-modified upconversion nanoparticles (UCNPs) as the luminescence core and gene carrier, while aptamers served as the DNA nanotrain to load DOX. Finally, the prepared nanotheranostic agent displayed good targetability, high cell apoptosis ratio (93.04%) with quite lower concentration than the LC50 of DOX, and obvious inhibition on tumor growth.

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MMP-8-Responsive Polyethylene Glycol Hydrogel for Intraoral Drug Delivery

Journal of Dental Research ◽

10.1177/0022034519831931 ◽

2019 ◽

Vol 98 (5) ◽

pp. 564-571 ◽

Cited By ~ 9

Author(s):

J. Guo ◽

H. Sun ◽

W. Lei ◽

Y. Tang ◽

S. Hong ◽

...

Keyword(s):

Drug Delivery ◽

Polyethylene Glycol ◽

High Performance ◽

Oral Diseases ◽

On Demand ◽

Michael Type Addition ◽

Minocycline Hydrochloride ◽

Environmentally Sensitive ◽

Localized Drug Delivery

Currently available drug delivery systems for oral diseases suffer from short retention time and poor local concentrations at the target site. A biodegradable stimulus-responsive hydrogel was synthesized in the present study to evaluate its application as an environmentally sensitive carrier for on-demand intraoral drug delivery. The hydrogel was synthesized from diacrylate-containing polyethylene glycol–based scaffolds and a cysteine-terminated peptide crosslinker (CGPQG↓IWGQC) via a Michael-type addition reaction. Because CGPQG↓IWGQC can be cleaved by matrix metalloproteinase 8 (MMP-8), minocycline hydrochloride, bovine serum albumin, or an antibacterial peptide (KSL) was incorporated into the scaffolds to evaluate the MMP-8-responsive release behavior of the on-demand drug delivery system. Hydrogel characterization and gelation kinetics were examined with gel time, Fourier-transform infrared spectroscopy, scanning electron microscopy, and measurements of rheologic parameters. Degradation behavior and MMP-8-responsive drug release were performed by high-performance liquid chromatography and protein-specific assay. Biocompatibility evaluation indicated that the hydrogels were noncytotoxic. Antibacterial testing demonstrated that the released drugs were able to maintain bioactivity. Taken together, these results suggest that the MMP-8-sensitive hydrogel is a promising candidate for on-demand intraoral localized drug delivery. Because MMP-8 is one of the most important biomarkers for periodontitis, the MMP-8-responsive hydrogel has potential to be used for in situ adaptive degradation in response to chronic periodontitis and peri-implantitis. This notion has to be tested in animal models of periodontal disease.

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Formulation and Physical Characterization of Bio-Degradable Chitosan-Poloxamer Gel Base for Local Drug Delivery

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v10i4.4216 ◽

2020 ◽

Vol 10 (4) ◽

pp. 59-66 ◽

Cited By ~ 1

Author(s):

Prasanna T. Dahake ◽

Sudhindra M Baliga ◽

Triveni Punse ◽

Dinesh M Biyani ◽

Neha Raut ◽

...

Keyword(s):

Drug Delivery ◽

Physical Properties ◽

Physical And Mechanical Properties ◽

Local Drug Delivery ◽

Mechanical And Physical Properties ◽

In Situ Hydrogel ◽

The Mean ◽

Poloxamer Gel

Objective: Thermo-modulated in-situ hydrogel (TSHG) are formulated routinely utilizing poloxamer for extended drug release. However physical properties of such formulations may have some flaws, which can be rectified using a combination of polymers with better physical properties such as chitosan. The purpose of the present study was to fabricate biodegradable chitosan-poloxamer-based in-situ drug delivery systems and assessment of their physical properties. Methods: The present chitosan-poloxamer gel base was formulated using a two-stage method. Initially, chitosan gel was prepared by dissolving 1% w/w chitosan in glacial acetic acid. The poloxamer gel was prepared using “cold method”. The final chitosan-poloxamer gel base was prepared by mixing equal amounts of both solutions and evaluated for physical and mechanical properties. Result and Discussion: The DSC thermogram demonstrated no obvious interactions among ingredients or micellization temperature. The gelation temperature of the gel was between 27 and 330C. The pH was 7 with slight clarity. The viscosity of the gel ranged from 15.14 to 41.19 pa.s. The gel was syringable between 4-300C and biodegradable under physiological conditions. The mean particle size of the gel under SEM was found in the range of 300-554 nm. Conclusion: After the evaluation of the formulation, it can be concluded that all the ingredients in the gel showed good compatibility with each other, which could form a stable and homogeneous gel with favorable mechanical and physical properties. Keywords: chitosan, drug delivery system, hydrogels, poloxamer

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Connexin43 Mimetic Peptide-Loaded Light Responsive In Situ Forming Injectable Implants for Effective Drug Delivery to the Posterior Segment of the Eye

10.26226/morressier.57d6b2b6d462b8028d88dc20 ◽

2016 ◽

Author(s):

Rohit Bisht

Keyword(s):

Drug Delivery ◽

Posterior Segment ◽

Effective Drug ◽

Mimetic Peptide ◽

In Situ Forming

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Scaffolds for Drug Delivery in Tissue Engineering

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2008.1.2.1 ◽

2008 ◽

Vol 1 (2) ◽

pp. 113-123 ◽

Cited By ~ 2

Author(s):

Vikas V. Gaikwad ◽

Abasaheb B. Patil ◽

Madhuri V. Gaikwad

Keyword(s):

Drug Delivery ◽

Tissue Engineering ◽

Heart Diseases ◽

Cartilage Regeneration ◽

Tissue Growth ◽

The Body ◽

Patient Specific ◽

In Situ Gel ◽

Heart Muscle Cells

Scaffolds are used for drug delivery in tissue engineering as this system is a highly porous structure to allow tissue growth. Although several tissues in the body can regenerate, other tissue such as heart muscles and nerves lack regeneration in adults. However, these can be regenerated by supplying the cells generated using tissue engineering from outside. For instance, in many heart diseases, there is need for heart valve transplantation and unfortunately, within 10 years of initial valve replacement, 50–60% of patients will experience prosthesis associated problems requiring reoperation. This could be avoided by transplantation of heart muscle cells that can regenerate. Delivery of these cells to the respective tissues is not an easy task and this could be done with the help of scaffolds. In situ gel forming scaffolds can also be used for the bone and cartilage regeneration. They can be injected anywhere and can take the shape of a tissue defect, avoiding the need for patient specific scaffold prefabrication and they also have other advantages. Scaffolds are prepared by biodegradable material that result in minimal immune and inflammatory response. Some of the very important issues regarding scaffolds as drug delivery systems is reviewed in this article.

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A Strategy for Fabricating in Situ Topographical 3D Scaffolds Using 3D Printing and Pluronic F-127

SSRN Electronic Journal ◽

10.2139/ssrn.3455095 ◽

2019 ◽

Author(s):

JiUn Lee ◽

SooJung Chae ◽

Hyeongjin Lee ◽

GeunHyung Kim

Keyword(s):

3D Printing ◽

3D Scaffolds

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Drug Delivery Systems Based on Titania Nanotubes and Active Agents for Enhanced Osseointegration of Bone Implants

Current Medicinal Chemistry ◽

10.2174/0929867326666190726123229 ◽

2020 ◽

Vol 27 (6) ◽

pp. 854-902 ◽

Cited By ~ 5

Author(s):

Raluca Ion ◽

Madalina Georgiana Necula ◽

Anca Mazare ◽

Valentina Mitran ◽

Patricia Neacsu ◽

...

Keyword(s):

Drug Delivery ◽

Tio2 Nanotubes ◽

Therapeutic Agent ◽

Bone Defects ◽

Delivery Systems ◽

Antimicrobial Compounds ◽

Bone Implant ◽

Bioactive Agents ◽

Localized Drug Delivery ◽

Regeneration Of Bone

TiO2 nanotubes (TNTs) are attractive nanostructures for localized drug delivery. Owing to their excellent biocompatibility and physicochemical properties, numerous functionalizations of TNTs have been attempted for their use as therapeutic agent delivery platforms. In this review, we discuss the current advances in the applications of TNT-based delivery systems with an emphasis on the various functionalizations of TNTs for enhancing osteogenesis at the bone-implant interface and for preventing implant-related infection. Innovation of therapies for enhancing osteogenesis still represents a critical challenge in regeneration of bone defects. The overall concept focuses on the use of osteoconductive materials in combination with the use of osteoinductive or osteopromotive factors. In this context, we highlight the strategies for improving the functionality of TNTs, using five classes of bioactive agents: growth factors (GFs), statins, plant derived molecules, inorganic therapeutic ions/nanoparticles (NPs) and antimicrobial compounds.

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