scholarly journals Accelerating thrombolysis using a precision and clot-penetrating drug delivery strategy by nanoparticle-shelled microbubbles

2020 ◽  
Vol 6 (31) ◽  
pp. eaaz8204
Author(s):  
Siyu Wang ◽  
Xixi Guo ◽  
Weijun Xiu ◽  
Yang Liu ◽  
Lili Ren ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Drug Release ◽  
Controlled Delivery ◽  
Drug Penetration ◽  
Ultrasound Stimulation ◽  
Tissue Plasminogen ◽  
Residual Thrombus ◽  
Time Critical ◽  
Target Side

Conventional thrombolytic drugs for vascular blockage such as tissue plasminogen activator (tPA) are challenged by the low bioavailability, off-target side effects and limited penetration in thrombi, leading to delayed recanalization. We hypothesize that these challenges can be addressed with the targeted and controlled delivery of thrombolytic drugs or precision drug delivery. A porous and magnetic microbubble platform is developed to formulate tPA. This system can maintain the tPA activity during circulation, be magnetically guided to the thrombi, and then remotely activated for drug release. The ultrasound stimulation also improves the drug penetration into thrombi. In a mouse model of venous thrombosis, the residual thrombus decreased by 67.5% when compared to conventional injection of tPA. The penetration of tPA by ultrasound was up to several hundred micrometers in thrombi. This strategy not only improves the therapeutic efficacy but also accelerates the lytic rate, enabling it to be promising in time-critical thrombolytic therapy.

scholarly journals Overview of implantable and injectable biomaterials in immunotherapy

2021 ◽  
Vol 16 (1) ◽  
pp. 195-201
Author(s):  
Prerana Prakash ◽  
Pushpa Agrawal ◽  
AH Manjunatha Reddy
Keyword(s):  
Drug Delivery ◽  
Immune Response ◽  
Side Effects ◽  
Drug Release ◽  
Cancer Vaccines ◽  
Release Kinetics ◽  
Local Drug Delivery ◽  
Systemic Immune Response ◽  
Immunomodulatory Agents ◽  
Target Side

Immunotherapy has shown promising applications in cancer treatment as it boosts the systemic immune response. Existing immunotherapy strategies have certain drawbacks which can be addressed by engineered biomaterials. In this review, we focused on advanced immunotherapy methods involving implantable and injectable biomaterials for the treatment of cancer. Engineered biomaterials as carriers for immunomodulatory agents aid in the local drug delivery, thus reducing the frequency of off-target side effects. Also, biomaterial-based cancer vaccines have the potential to target specific tissues by finely altering the physical properties of the drug to achieve desired drug release kinetics.

Tyrosinase-responsive tumor-specific cascade amplification drug release system for melanoma therapy

2021 ◽  
Author(s):  
Dongdong Li ◽  
Xiaoxuan Zhou ◽  
Wei Zhang ◽  
Hongxia Xu ◽  
Bing Xiao ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Drug Release ◽  
Tumor Heterogeneity ◽  
Drug Delivery Systems ◽  
Drug Side Effects ◽  
Anticancer Efficacy ◽  
Cascade Amplification ◽  
Tumor Selective ◽  
Melanoma Therapy

Tumor-selective drug delivery could enhance anticancer efficacy and avoid drug side effects. However, because of tumor heterogeneity, current nanoparticle-based drug delivery systems rarely improve clinical outcomes significantly, commonly only reducing...

scholarly journals DR-5 and DLL-4 mAb Functionalized SLNs of Gamma-Secretase Inhibitors- An Approach for TNBC Treatment

2020 ◽  
Author(s):  
Mamta Kumari ◽  
Praveen T. Krishnamurthy ◽  
Sai kiran S. S. Pinduprolu ◽  
Piyong Sola
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Side Effects ◽  
Notch Signaling ◽  
Death Receptor ◽  
Death Receptor 5 ◽  
Gamma Secretase ◽  
Extrinsic Pathway ◽  
Cancer Subtypes ◽  
Target Side

Triple-negative breast cancer (TNBC) is the most aggressive and heterogeneous cancer subtypes. High rates of metastasis, poor prognosis, and drug resistance are the major problems associated with TNBC. The current chemotherapeutics eliminate only the bulk tumor cells (non-BCSCs) and do not affect breast cancer stem cells (BCSCs). The BCSCs which are left behind after chemotherapy is reported to promote recurrence and metastasis of TNBC. Death receptor-5 (DR-5) is exclusively expressed in TNBCs and mediates the extrinsic pathway of apoptosis. DR-5, therefore, can be exploited for targeted drug delivery and to induce apoptosis. Gamma-secretase mediated Notch signaling in BCSCs regulates its proliferation, differentiation, and metastasis. The endogenous ligand, Delta-like ligand 4 (DLL4), is reported to activate this Notch signaling in TNBC. Blocking this signaling pathway using both gamma-secretase inhibitors (GSIs) and DLL4 monoclonal antibody (mAb) may produce synergistic benefits. Further, the GSIs (DAPT, LY-411575, RO4929097, MK0752, etc.) suffer from poor bioavailability and off-target side effects such as diarrhea, suppression of lymphopoiesis, headache, hypertension, fatigue, and ventricular dysfunctions. In this hypothesis, we discuss Solid lipid nanoparticles (SLNs) based drug delivery systems containing GSIs and surface modified with DR-5 and DLL4 monoclonal antibodies (mAb) to effectivity target and treat TNBC. The delivery system is designed to deliver the drug cargo precisely to TNBCs through its DR-5 receptors and hence expected to reduce the off-target side effects of GSIs. Further, DLL4 mAb and GSIs are expected to act synergistically to block the Notch signal mediated BCSCs proliferation, differentiation, and metastasis.

scholarly journals ncRNAs in Therapeutics: Challenges and Limitations in Nucleic Acid-Based Drug Delivery

2021 ◽  
Vol 22 (21) ◽  
pp. 11596
Author(s):  
Miguel Hueso ◽  
Adrián Mallén ◽  
Marc Suñé-Pou ◽  
Josep M. Aran ◽  
Josep M. Suñé-Negre ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Clinical Practice ◽  
Cardiovascular Diseases ◽  
Side Effects ◽  
Future Trends ◽  
Biological Mechanisms ◽  
Key Issues ◽  
Non Coding Rnas ◽  
Therapeutic Tools ◽  
Target Side

Non-coding RNAs (ncRNAs) are emerging therapeutic tools but there are barriers to their translation to clinical practice. Key issues concern the specificity of the targets, the delivery of the molecules, and their stability, while avoiding “on-target” and “off-target” side effects. In this “ncRNA in therapeutics’’ issue, we collect several studies of the differential expression of ncRNAs in cardiovascular diseases, bone metabolism-related disorders, neurology, and oncology, and their potential to be used as biomarkers or therapeutic targets. Moreover, we review recent advances in the use of antisense ncRNAs in targeted therapies with a particular emphasis on their basic biological mechanisms, their translational potential, and future trends.

scholarly journals Investigation of Inertial Cavitation of Sonosensitive and Biocompatible Nanoparticles in Flow - Through Tissue- Mimicking Phantoms Employing Focused Ultrasound

2021 ◽  
Vol 7 (2) ◽  
pp. 163-166
Author(s):  
Benedikt George ◽  
Ula Savšek ◽  
Dagmar Fischer ◽  
Helmut Ermert ◽  
Stefan J. Rupitsch
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Drug Release ◽  
Focused Ultrasound ◽  
Vascular System ◽  
Drug Carriers ◽  
Inertial Cavitation ◽  
Cavitation Effect ◽  
Flow Through ◽  
Delivery Approach

Abstract A promising approach to drug delivery applications for chemotherapeutics is the use of drug carriers to reduce the total amount of cytostatics, minimizing side effects. In addition, the carriers, loaded with the drug, can be guided to the tumorous tissue via the vascular system, which enables a local drug release (LDR). In our case, LDR is activated due to the sonosensitive behavior of the nanocapsules by inertial cavitation (IC) caused by focused ultrasound (FUS). Thereby, IC is excited by employing sound pressures within the recommended limit allowed for diagnostic ultrasound. In order to verify this drug delivery approach for its clinical suitability, a tissue-mimicking flow -through phantom, containing a small vessel, is used. Investigations have shown that the drug releasing cavitation effect associated with the sonosensitive and biocompatible nanocapsules also occurs in fine vessel structures, even in the case of moving particles and vessel diameters dc smaller than the wavelength λ.

Targeted Drug Therapy to Overcome Chemoresistance in Triple-negative Breast Cancer

2020 ◽  
Vol 20 (8) ◽  
pp. 559-572
Author(s):  
Mamta Kumari ◽  
Praveen Thaggikuppe Krishnamurthy ◽  
Piyong Sola
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Side Effects ◽  
Triple Negative Breast Cancer ◽  
Anticancer Agents ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Cancer Subtype ◽  
Prevent Tumor Growth ◽  
Target Side

Triple-negative Breast Cancer (TNBC) is the most aggressive and prevailing breast cancer subtype. The chemotherapeutics used in the treatment of TNBC suffer from chemoresistance, dose-limiting toxicities and off-target side effects. As a result, conventional chemotherapeutics are unable to prevent tumor growth, metastasis and result in failure of therapy. Various new targets such as BCSCs surface markers (CD44, CD133, ALDH1), signaling pathways (IL-6/JAK/STAT3, notch), pro and anti-apoptotic proteins (Bcl-2, Bcl-xL, DR4, DR5), hypoxic factors (HIF-1α, HIF-2α) and drug efflux transporters (ABCC1, ABCG2 and ABCB1) have been exploited to treat TNBC. Further, to improve the efficacy and safety of conventional chemotherapeutics, researchers have tried to deliver anticancer agents specifically to the TNBCs using nanocarrier based drug delivery. In this review, an effort has been made to highlight the various factors responsible for the chemoresistance in TNBC, novel molecular targets of TNBC and nano-delivery systems employed to achieve sitespecific drug delivery to improve efficacy and reduce off-target side effects.

scholarly journals Onychomycosis: current understanding and strategies for enhancing drug delivery into human nail tissue

2020 ◽  
Vol 12 ◽  
Author(s):  
Rabia Aslam ◽  
Talib Hussain ◽  
Abid Mehmood Yousaf ◽  
Muhammad Usman Ghori ◽  
Ikram Ullah Khan ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Infectious Disease ◽  
Drug Delivery ◽  
Side Effects ◽  
Oral Therapy ◽  
Drug Penetration ◽  
Therapeutic Approaches ◽  
Nail Bed ◽  
Mechanical Methods

Background: Onychomycosis is by far the most common finger or toe nail fungal infectious disease caused by dermatophytes, non-dermatophytic molds or yeast. It accounts for 50% of the total nail disorders, and affects patients physically, socially, and psychologically and can seriously influence their quality of life. Objectives: Oral antifungals are routinely used to treat the nail fungal disease; however oral therapy is associated with severe side effects and longer treatment times. In recent years, drug delivery directly into the nail or nail bed has gained attention and various topical products have been tested that can cure the disease when applied topically or transungually. Nevertheless, drug penetration into and through the nail is not straightforward and requires chemicals to improve its permeability or by applying physical stress to promote drug penetration into and through the nail. Topics covered: This lucid review presents an overview of various causes of onychomycosis, current therapeutic approaches, and efforts aimed at increasing the permeability of nails through various strategies such as chemical, physical and mechanical methods for permeation enhancement. Conclusion: Various strategies have been proposed for the treatment of onychomycosis, however, much research into a more precise and effective therapy is still required.

NATURAPOLYCEUTICS – EMERGING SCIENCE & TECHNOLOGY IN DRUG DELIVERY SYSTEM.

2020 ◽  
Vol 10 ◽  
Author(s):  
Nishant Gaur ◽  
Shikha Srivastava ◽  
Nayyar Parvez
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Drug Release ◽  
Drug Delivery Systems ◽  
Development Process ◽  
Biological Properties ◽  
Natural Polymer ◽  
Natural Polymers ◽  
Science Technology ◽  
Constant Rate

: This review mainly put emphasis on properties and recent applications of various natural polymers (Naturapolyceutics) used in drug delivery development process including alginate, chitosan, starch, cellulose, gums etc. Naturapolyceutics is the platform that blends natural polymers and Pharmaceutics for the design and development of drug delivery systems. Natural polymers due to their biological properties, sustainability, human and eco-friendliness are promising in this field. Polymers as an excipient influence drug release and should be compatible, non-toxic, stable, economic etc. Nowadays, due to many problems associated with drug release and side effects manufacturers are inclined towards using natural polymers. In future, these natural materials have many advantages over synthetic ones as they are non-toxic and most important, a constant rate of drug release can be achieved from a natural polymer based controlled release device’s.

scholarly journals FORMULATION AND EVALUATION OF METFORMIN HYDROCHLORIDE SUSTAINED RELEASE MATRIX TABLETS

2021 ◽  
pp. 82-88
Author(s):  
SAHIDUL ALAM ◽  
AMLAN BISHAL ◽  
BRATATI BANDYOPADHYAY
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Drug Release ◽  
Sustained Release ◽  
Xanthan Gum ◽  
Matrix Tablets ◽  
Fickian Diffusion ◽  
Release Mechanism ◽  
Metformin Hydrochloride ◽  
Major Advance

Objective: Now a days as very few antidiabetic drugs are coming out of research and development and some existing drugs are showing several side effects when administered orally, multiple times in a day, hence change in the operation is a suitable and optimized way to make some drug more effective by slight alteration in the drug delivery. Matrix type drug delivery systems of an antidiabetic drug like Metformin Hydrochloride, is an interesting and promising option when developing an oral sustained release system Methods: An appropriately designed controlled release drug delivery system can be a major advance towards solving problems concerning the targeting of a drug to a specific organ or tissue and controlling the rate of drug delivery to the target sites. This research work is made in designing of sustained release dosage form of Metformin Hydrochloride by wet granulation method employing both Xanthan Gum and Hydroxy Propyl Methyl Cellulose (HPMC K4M) as a rate controlling polymer. Results: The development of oral sustained release systems has been a challenge to formulation scientists due to their inability to restrain and localize the system at targeted areas of the gastrointestinal tract. From all the formulation trial batches, formulation F7 shows the best results. It has been observed that HPMC K4M alone cannot give satisfactory drug release profile but the blend of HPMC K4M and Xanthan gum together give the best drug release kinetics. Conclusion: The drug release mechanism from the matrix tablets follows Fickian diffusion with first order kinetics. Thus, sustained release matrix tablets of metformin hydrochloride can be expected to reduce the frequency of administration and decrease the dose dependent side effects

Cancer cell membrane-coated nanogels as redox/pH dual-responsive drug carrier for tumor-targeted therapy

2021 ◽  
Author(s):  
Junjie Deng ◽  
Weide Xu ◽  
Jilong Wang ◽  
Qinghua Li ◽  
Chenghu Wu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Therapy ◽  
Side Effects ◽  
Drug Release ◽  
Cell Membrane ◽  
Cancer Cell ◽  
Drug Carrier ◽  
On Demand ◽  
Dual Responsive

Nanocarriers have shown great advantages in increasing the efficiency of drug delivery and reducing the side effects. However, the lack of targeting and on-demand drug release will seriously limit their...

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