GSH-Responsive Drug Delivery System for Active Therapy and Reducing the Side Effects of Bleomycin

The study demonstrates the importance of the weight ratio of F127 and gelatin in forming size selective nanoconjugate through a thermal relaxation approach and its potential as an efficient drug delivery system of doxorubicin with reduced side effects.

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Nanotech drug delivery system: The perfect physio-Chemical deal for biological command

Journal of Pharmaceutical and Biological Sciences ◽

10.18231/j.jpbs.2021.010 ◽

2021 ◽

Vol 9 (2) ◽

pp. 73-80

Author(s):

Yogranjan Singh ◽

Kaustubh Gurnani ◽

G. K. Satpute

Keyword(s):

Drug Delivery ◽

Side Effects ◽

Drug Delivery System ◽

Delivery System ◽

Conventional Therapy ◽

Therapeutic Agents ◽

Prime Concern ◽

Key Techniques ◽

Near Future

The application of nanotechnology in drug delivery is offering several exhilarating possibilities not only in healthcare but also in agriculture. Nanoparticles combined with the therapeutic agents have a proven edge over problems associated with conventional therapy; however, some issues like side effects and toxicity are still under debate and are of prime concern in utilization in biological systems. Herein, we discuss the role of nanotech drug delivery system mostly in animal and plants- highlighting the comparative accounts of the key techniques for designing of drug in animals and plants, the challenges therein, the important nanoparticles being used in both the area and prospects of the field in the near future.

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Synergistic effect of folate-conjugated polymers and 5-fluorouracil in the treatment of colon cancer

Cancer Nanotechnology ◽

10.1186/s12645-021-00104-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Gabriela Siemiaszko ◽

Katarzyna Niemirowicz-Laskowska ◽

Karolina H. Markiewicz ◽

Iwona Misztalewska-Turkowicz ◽

Ewelina Dudź ◽

...

Keyword(s):

Drug Delivery ◽

Colon Cancer ◽

Folic Acid ◽

Side Effects ◽

Drug Delivery System ◽

Delivery System ◽

The Body ◽

Effective Therapy ◽

Controlled Polymerization ◽

Micellar Systems

Abstract Background In recent years, targeted drug delivery strategies have received special attention from the scientific world due to advantages such as more effective therapy and reduction of side effects. The principle of operation is delayed excretion from the bloodstream of the drug delivery system compared to the drug itself, as well as facilitated penetration into diseased cells thanks to the use of ligands recognized by appropriate receptors. Particularly interesting drug carriers are amphiphilic copolymers that form nano-sized micelles with a drug, which can release the drug at a specific place in the body under the influence of appropriate stimuli. Results We describe the synthesis of the diblock polymer, poly(2-hydroxyethyl acrylate)-b-poly(N-vinylcaprolactam) using RAFT/MADIX (Reversible Addition-Fragmentation chain Transfer/MAcromolecular Design by Interchange of Xanthate) controlled polymerization affording polymers with good dispersity according to SEC (Size-Exclusion Chromatography). Some post-modifications of the polymer with folic acid were then performed as evidenced by NMR (Nuclear Magnetic Resonance), UV–Vis (UltraViolet–Visible) and FT-IR (Fourier-Transform Infrared) spectroscopy, and TGA (ThermoGravimetric Analysis). The formation of stable micellar systems from polymers with and without the drug, 5-fluorouracil, was confirmed by DLS (Dynamic Light Scattering) and zeta potential measurements, and TEM (Transmission Eelectron Microscopy) imaging. Finally, the cloud point of the polymers was investigated, which turned out to be close to the temperature of the human body. Most importantly, these micellar systems have been explored as a drug delivery system against colon cancer, showing increased cytotoxicity compared to the drug alone. This effect was achieved due to the easier cellular uptake by the interaction of folic acid and its receptors on the surface of cancer cells. Conclusions The presented results constitute a solid foundation for the implementation of a nano-sized drug delivery system containing folic acid for practical use in the treatment of drug-resistant cancer, as well as more effective therapy with fewer side effects. Graphical Abstract

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A Review on Novel Drug Delivery System: Microsponges

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v7i04.10652 ◽

2017 ◽

Vol 7 (04) ◽

Author(s):

Soumya Singh ◽

Dherendra Sahu

Keyword(s):

Drug Delivery ◽

Side Effects ◽

Drug Delivery System ◽

Delivery System ◽

Active Ingredient ◽

Suspension Polymerization ◽

Rapid Evolution ◽

Active Agent ◽

Systemic Exposure ◽

Emulsion System

Recent research on idealizing drug delivery system which is progressing at a prodigious rate and aims at development of drug delivery system (DDS), with maximum therapeutic advantages of drug delivery, thus resulting in safe and effective management of disease. More and more developments in delivery systems are being integrated to optimize the efficacy and cost effectiveness of the therapy. New classes of pharmaceuticals, biopharmaceuticals are fueling the rapid evolution of drug delivery technology. Microsponge technology has been introduced in topical drug products to facilitate the controlled release of active drug into the skin in order to reduce systemic exposure and minimize local cutaneous reactions to active drugs. Microsponge consists of microporous beads loaded with active agent. When applied to the skin, the microsponge releases its active ingredient on a time mode and also in response to other stimuli (rubbing, temperature, pH etc.) that are used mostly for topical and recently for oral administration Microsponges are porous, polymeric microspheres that are mostly used for prolonged topical administration. Microsponges are designed to deliver a pharmaceutically active ingredient efficiently at minimum dose and also to enhance stability, reduce side effects, and modify drug release profiles. Microsponges are prepared by several methods utilizing emulsion system or by suspension polymerization in a liquid–liquid system. The most common emulsion system used is oil-in-water (o/w), with the microsponges being produced by the emulsion solvent diffusion (ESD) method. Microsponge delivery system (MDS) can provide increased efficacy for topically active agents with enhanced safety, extended product stability, enhanced formulation flexibility, reduced side effects and improved aesthetic properties in an efficient and novel manner. In addition these are non-irritating, non-mutagenic, non-allergenic, and nontoxic. The present review introduces microsponge technology in great detail.

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Immunoliposomes in Acute Myeloid Leukaemia Therapy: An Overview of Possible Targets and Obstacles

Current Medicinal Chemistry ◽

10.2174/0929867326666190517114450 ◽

2019 ◽

Vol 26 (28) ◽

pp. 5278-5292 ◽

Cited By ~ 1

Author(s):

Aditi Singh ◽

Nikolai Norevik Myklebust ◽

Sarah Marie Vie Furevik ◽

Ragnhild Haugse ◽

Lars Herfindal

Keyword(s):

Drug Delivery ◽

Stem Cells ◽

Bone Marrow ◽

Side Effects ◽

Acute Myeloid Leukaemia ◽

Myeloid Leukaemia ◽

Drug Delivery System ◽

Delivery System ◽

Target Cells ◽

Acute Myeloid

:Acute Myeloid Leukaemia (AML) is the neoplastic transformation of Hematopoietic Stem Cells (HSC) and relapsed disease is a major challenge in the treatment. Despite technological advances in the field of medicine and our heightened knowledge regarding the pathogenesis of AML, the initial therapy of “7+3” Cytarabine and Daunorubicin has remained mainly unchanged since 1973. AML is a disease of the elderly, and increased morbidity in this patient group does not allow the full use of the treatment and drug-resistant relapse is common.:Nanocarriers are drug-delivery systems that can be used to transport drugs to the bone marrow and target Leukemic Stem Cells (LSC), conferring less side-effects compared to the free-drug alternative. Nanocarriers also can be used to favour the transport of drugs that otherwise would not have been used clinically due to toxicity and poor efficacy. Liposomes are a type of nanocarrier that can be used as a dedicated drug delivery system, which can also have active ligands on the surface in order to interact with antigens on the target cells or tissues. In addition to using small molecules, it is possible to attach antibodies to the liposome surface, generating so-called immunoliposomes. By using immunoliposomes as a drug-delivery system, it is possible to minimize the toxic side effects caused by the chemotherapeutic drug on healthy organs, and at the same time direct the drugs towards the remaining AML blasts and stem cells.:This article aims to explore the possibilities of using immunoliposomes as a drug carrier in AML therapy. Emphasis will be on possible target molecules on the AML cells, leukaemic stem cells, as well as bone marrow constituents relevant to AML therapy. Further, some conditions and precautions that must be met for immunoliposomes to be used in AML therapy will be discussed.

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MAGNETIC MICROSPHERE AN EMERGING DRUG DELIVERY SYSTEM

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i6.17284 ◽

2017 ◽

Vol 10 (6) ◽

pp. 54 ◽

Cited By ~ 1

Author(s):

Diksha Sharma ◽

Abhishek Sharma

Keyword(s):

Drug Delivery ◽

Side Effects ◽

Drug Delivery System ◽

Delivery System ◽

Targeted Drug Delivery ◽

The Body ◽

Magnetic Microspheres ◽

Magnetic Microsphere ◽

Targeted Drug ◽

Novel Drug

The drug delivery system has been advanced to release the drug according to the body requirement during the entire period of treatment and also for the delivery at the targeted site. Several novel drug delivery systems have emerged encompassing different route of administration to achieve controlled and targeted drug delivery, magnetic microsphere carrier being one of them. Magnetic microsphere is an alternative to traditional radiation methods. As the traditional radiation methods use highly penetrating radiation that is absorbed throughout the body and cause side effects hence its use is limited. Therefore, a safe and effective alternate is needed like magnetic microsphere. The excessive circulating drug particles are minimized by this delivery system. Moreover, the aim of specific targeting is to enhance the effectiveness of drug delivery and at the same time to lessen the toxicity and side effects. Magnetic carriers receive magnetic responses to a magnetic field from incorporated materials that are used for magnetic microsphere are chitosan, dextran, etc. One of the most utilized magnetic microspheres is serum albumine whether from human or other suitable animals. Drug release from the albumin microsphere can be controlled by various stabilization procedures. Overall, the targeted magnetic microsphere is much valuable novel drug delivery system for what more work have to be done. By knowing the importance of all this, the present paper reviews the mechanism, preparation, and applications of magnetic microspheres. As the targeted drug delivery system implies selective and effective localization of drug into the target at therapeutic concentrations with limited access to non-target sites. Magnetic microspheres hold great promises for reaching the goal of controlled and site-specific drug delivery.

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pH-Responsive Alginate-Based Microparticles for Colon-Targeted Delivery of Pure Cyclosporine A Crystals to Treat Ulcerative Colitis

Pharmaceutics ◽

10.3390/pharmaceutics13091412 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1412

Author(s):

Murtada A. Oshi ◽

Juho Lee ◽

Jihyun Kim ◽

Nurhasni Hasan ◽

Eunok Im ◽

...

Keyword(s):

Ulcerative Colitis ◽

Drug Delivery ◽

Side Effects ◽

Drug Delivery System ◽

Delivery System ◽

Cyclosporine A ◽

Targeted Delivery ◽

Drug Loading ◽

Systemic Absorption ◽

Systemic Side Effects

Cyclosporine A (CsA) is a potent immunosuppressant for treating ulcerative colitis (UC). However, owing to severe systemic side effects, CsA application in UC therapy remains limited. Herein, a colon-targeted drug delivery system consisting of CsA crystals (CsAc)-loaded, Eudragit S 100 (ES)-coated alginate microparticles (CsAc-EAMPs) was established to minimize systemic side effects and enhance the therapeutic efficacy of CsA. Homogeneously-sized CsAs (3.1 ± 0.9 μm) were prepared by anti-solvent precipitation, followed by the fabrication of 47.1 ± 6.5 μm-sized CsAc-EAMPs via ionic gelation and ES coating. CsAc-EAMPs exhibited a high drug loading capacity (48 ± 5%) and a CsA encapsulation efficacy of 77 ± 9%. The in vitro drug release study revealed that CsA release from CsAc-EAMPs was suppressed under conditions simulating the stomach and small intestine, resulting in minimized systemic absorption and side effects. Following exposure to the simulated colon conditions, along with ES dissolution and disintegration of alginate microparticles, CsA was released from CsAc-EAMPs, exhibiting a sustained-release profile for up to 24 h after administration. Given the effective colonic delivery of CsA molecules, CsAc-EAMPs conferred enhanced anti-inflammatory activity in mouse model of dextran sulfate sodium (DSS)-induced colitis. These findings suggest that CsAc-EAMPs is a promising drug delivery system for treating UC.

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Ultrasound-Based Drug Delivery System

Current Medicinal Chemistry ◽

10.2174/0929867328666210617103905 ◽

2021 ◽

Vol 28 ◽

Author(s):

Wei-Wei Ren ◽

Shi-Hao Xu ◽

Li-Ping Sun ◽

Kun Zhang

Keyword(s):

Drug Delivery ◽

Side Effects ◽

Drug Delivery System ◽

Delivery System ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Research Progress ◽

Cancer Drugs ◽

Nano Drug Delivery ◽

Anti Cancer

: Cancer still represents a leading threat to human health worldwide. The effective usage of anti-cancer drugs can reduce patients’ clinical symptoms and extend the life span. Current anti-cancer strategies include chemotherapy, traditional Chinese medicine, biopharmaceuticals, and the latest targeted therapy. However, due to the complexity and heterogeneity of tumors, serious side effects may result from the direct use of anti-cancer drugs. Besides, the current therapeutic strategies failed to effectively alleviate metastasized tumors. Recently, an ultrasound-mediated nano-drug delivery system has become an increasingly important treatment strategy. Due to its ability to enhance efficacy and reduce toxic side effects, it has become a research hotspot in the field of biomedicine. In this review, we introduced the latest research progress of the ultrasound-responsive nano-drug delivery systems and the possible mechanisms of ultrasound acting on the carrier to change the structure or conformation as well as to realize the controlled release. In addition, the progress in ultrasound responsive nano-drug delivery systems will also be briefly summarized.

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Recent Advances in Nanocarrier-Assisted Therapeutics Delivery Systems

Pharmaceutics ◽

10.3390/pharmaceutics12090837 ◽

2020 ◽

Vol 12 (9) ◽

pp. 837 ◽

Cited By ~ 1

Author(s):

Shi Su ◽

Peter M. Kang

Keyword(s):

Drug Delivery ◽

Side Effects ◽

Drug Delivery System ◽

Delivery System ◽

Therapeutic Efficacy ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Stimuli Responsive ◽

Surface Stabilization ◽

Recent Advances

Nanotechnologies have attracted increasing attention in their application in medicine, especially in the development of new drug delivery systems. With the help of nano-sized carriers, drugs can reach specific diseased areas, prolonging therapeutic efficacy while decreasing undesired side-effects. In addition, recent nanotechnological advances, such as surface stabilization and stimuli-responsive functionalization have also significantly improved the targeting capacity and therapeutic efficacy of the nanocarrier assisted drug delivery system. In this review, we evaluate recent advances in the development of different nanocarriers and their applications in therapeutics delivery.

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Improved Safety and Anti-Glioblastoma Efficacy of CAT3-Encapsulated SMEDDS through Metabolism Modification

Molecules ◽

10.3390/molecules26020484 ◽

2021 ◽

Vol 26 (2) ◽

pp. 484

Author(s):

Hongliang Wang ◽

Lin Li ◽

Jun Ye ◽

Wujun Dong ◽

Xing Zhang ◽

...

Keyword(s):

Drug Delivery ◽

Gastrointestinal Tract ◽

Side Effects ◽

Drug Delivery System ◽

Delivery System ◽

Lymphatic Transport ◽

Pharmacokinetic Parameters ◽

Gastrointestinal Side Effects ◽

The Brain

13a-(S)-3-pivaloyloxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (CAT3) is a novel oral anti-glioma pro-drug with a potent anti-tumor effect against temozolomide-resistant glioma. 13a(S)-3-hydroxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (PF403) is the active in vivo lipase degradation metabolite of CAT3. Both CAT3 and PF403 can penetrate the blood–brain barrier to cause an anti-glioma effect. However, PF403, which is produced in the gastrointestinal tract and plasma, causes significant gastrointestinal side effects, limiting the clinical application of CAT3. The objective of this paper was to propose a metabolism modification for CAT3 using a self-microemulsifying drug delivery system (SMEDDS), in order to reduce the generation of PF403 in the gastrointestinal tract and plasma, as well as increase the bioavailability of CAT3 in vivo and the amount of anti-tumor substances in the brain. Thus, a CAT3-loaded self-microemulsifying drug delivery system (CAT3-SMEDDS) was prepared, and its physicochemical characterization was systematically carried out. Next, the pharmacokinetic parameters of CAT3 and its metabolite in the rats’ plasma and brain were measured. Furthermore, the in vivo anti-glioma effects and safety of CAT3-SMEDDS were evaluated. Finally, Caco-2 cell uptake, MDCK monolayer cellular transfer, and the intestinal lymphatic transport mechanisms of SMEDDS were investigated in vitro and in vivo. Results show that CAT3-SMEDDS was able to form nanoemulsion droplets in artificial gastrointestinal fluid within 1 min, displaying an ideal particle size (15–30 nm), positive charge (5–9 mV), and controlled release behavior. CAT3-SMEDDS increased the membrane permeability of CAT3 by 3.9-fold and promoted intestinal lymphatic transport. Hence, the bioavailability of CAT3 was increased 79% and the level of its metabolite, PF403, was decreased to 49%. Moreover, the concentrations of CAT3 and PF403 were increased 2–6-fold and 1.3–7.2-fold, respectively, in the brain. Therefore, the anti-glioma effect in the orthotopic models was improved with CAT3-SMEDDS compared with CAT3 in 21 days. Additionally, CAT3-SMEDDS reduced the gastrointestinal side effects of CAT3, such as severe diarrhea, necrosis, and edema, and observed less inflammatory cell infiltration in the gastrointestinal tract, compared with the bare CAT3. Our work reveals that, through the metabolism modification effect, SMEDDS can improve the bioavailability of CAT3 and reduce the generation of PF403 in the gastrointestinal tract and plasma. Therefore, it has the potential to increase the anti-glioma effect and reduce the gastrointestinal side effects of CAT3 simultaneously.

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