Recent Advances in Non-Invasive Delivery of Macromolecules using Nanoparticulate Carriers System

Background: The drug delivery of macromolecules such as proteins and peptides has become an important area of research and represents the fastest expanding share of the market for human medicines. The most common method for delivering macromolecules is parenterally. However parenteral administration of some therapeutic macromolecules has not been effective because of their rapid clearance from the body. As a result, most macromolecules are only therapeutically useful after multiple injections, which causes poor compliance and systemic side effects. Methods: Therefore, there is a need to improve delivery of therapeutic macromolecules to enable non-invasive delivery routes, less frequent dosing through controlled-release drug delivery, and improved drug targeting to increase efficacy and reduce side effects. Result: Non-invasive administration routes such as intranasal, pulmonary, transdermal, ocular and oral delivery have been attempted intensively by formulating macromolecules into nanoparticulate carriers system such as polymeric and lipidic nanoparticles. Conclusion: This review discusses barriers to drug delivery and current formulation technologies to overcome the unfavorable properties of macromolecules via non-invasive delivery (mainly intranasal, pulmonary, transdermal oral and ocular) with a focus on nanoparticulate carrier systems. This review also provided a summary and discussion of recent data on non-invasive delivery of macromolecules using nanoparticulate formulations.

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New Trends in Drug Delivery Systems for Veterinary Applications

Pharmaceutical Nanotechnology ◽

10.2174/2211738508666200613214548 ◽

2020 ◽

Vol 08 ◽

Author(s):

Classius Ferreira da Silva ◽

Taline Almeida ◽

Raquel de Melo Barbosa ◽

Juliana Cardeiro Cardoso ◽

Margaretha Morsink ◽

...

Keyword(s):

Drug Delivery ◽

Side Effects ◽

Drug Delivery Systems ◽

Academic Research ◽

Delivery Systems ◽

Global Market ◽

Animal Origin ◽

Veterinary Drug ◽

Administration Routes ◽

Delivery Routes

Background: The veterinary pharmaceutical industry has shown significant growth in recent decades. Several factors contribute to this increase as the demand for the improvement of the quality of life of both domestic and wild animals, together with the need to improve the quality, productivity, and safety of foodstuffs of animal origin. Methods: The goal of this work was to identify the most suitable medicines for animals that focus on drug delivery routes as those for humans, although they may have different devices, such as collars and ear tags. Results: Recent advances in drug delivery systems for veterinary use are discussed, both from academic research and the global market. The administration routes commonly used for veterinary medicines are also explored, while special attention is given to the latest technological trends to improve the drug performance, reducing the number of doses, animal stress, and side effects. Conclusion: Drug delivery system in veterinary decreased the number of doses, side effects, and animal stress are a small fraction of the benefits of veterinary drug delivery systems and represent a significant increase in profit for the industry; also, it demands investments in research regarding the quality, safety, and efficacy of the drug and the drug delivery systems.

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Biocompatible Polymers and their Potential Biomedical Applications: A Review

Current Pharmaceutical Design ◽

10.2174/1381612825999191011105148 ◽

2019 ◽

Vol 25 (34) ◽

pp. 3608-3619 ◽

Cited By ~ 3

Author(s):

Uzma Arif ◽

Sajjad Haider ◽

Adnan Haider ◽

Naeem Khan ◽

Abdulaziz A. Alghyamah ◽

...

Keyword(s):

Drug Delivery ◽

Side Effects ◽

Biomedical Applications ◽

Living System ◽

Health Condition ◽

The Body ◽

Biocompatible Polymers ◽

Nano Technology ◽

Artificial Grafts ◽

Immunological Reactions

Background: Biocompatible polymers are gaining great interest in the field of biomedical applications. The term biocompatibility refers to the suitability of a polymer to body and body fluids exposure. Biocompatible polymers are both synthetic (man-made) and natural and aid in the close vicinity of a living system or work in intimacy with living cells. These are used to gauge, treat, boost, or substitute any tissue, organ or function of the body. A biocompatible polymer improves body functions without altering its normal functioning and triggering allergies or other side effects. It encompasses advances in tissue culture, tissue scaffolds, implantation, artificial grafts, wound fabrication, controlled drug delivery, bone filler material, etc. Objectives: This review provides an insight into the remarkable contribution made by some well-known biopolymers such as polylactic-co-glycolic acid, poly(ε-caprolactone) (PCL), polyLactic Acid, poly(3- hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), Chitosan and Cellulose in the therapeutic measure for many biomedical applications. Methods: : Various techniques and methods have made biopolymers more significant in the biomedical fields such as augmentation (replaced petroleum based polymers), film processing, injection modeling, blow molding techniques, controlled / implantable drug delivery devices, biological grafting, nano technology, tissue engineering etc. Results: The fore mentioned techniques and other advanced techniques have resulted in improved biocompatibility, nontoxicity, renewability, mild processing conditions, health condition, reduced immunological reactions and minimized side effects that would occur if synthetic polymers are used in a host cell. Conclusion: Biopolymers have brought effective and attainable targets in pharmaceutics and therapeutics. There are huge numbers of biopolymers reported in the literature that has been used effectively and extensively.

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Polymer-Drug Conjugates as Nanotheranostic Agents

Journal of Nanotheranostics ◽

10.3390/jnt2010005 ◽

2021 ◽

Vol 2 (1) ◽

pp. 63-81

Author(s):

Sajana Manandhar ◽

Erica Sjöholm ◽

Johan Bobacka ◽

Jessica M. Rosenholm ◽

Kuldeep K. Bansal

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Treatment Options ◽

The Body ◽

Drug Conjugates ◽

Imaging Characteristics ◽

Wide Range ◽

Systemic Side Effects ◽

Theranostic Agents ◽

The Stability

Since the last decade, the polymer-drug conjugate (PDC) approach has emerged as one of the most promising drug-delivery technologies owing to several benefits like circumventing premature drug release, offering controlled and targeted drug delivery, improving the stability, safety, and kinetics of conjugated drugs, and so forth. In recent years, PDC technology has advanced with the objective to further enhance the treatment outcomes by integrating nanotechnology and multifunctional characteristics into these systems. One such development is the ability of PDCs to act as theranostic agents, permitting simultaneous diagnosis and treatment options. Theranostic nanocarriers offer the opportunity to track the distribution of PDCs within the body and help to localize the diseased site. This characteristic is of particular interest, especially among those therapeutic approaches where external stimuli are supposed to be applied for abrupt drug release at the target site for localized delivery to avoid systemic side effects (e.g., Visudyne®). Thus, with the help of this review article, we are presenting the most recent updates in the domain of PDCs as nanotheranostic agents. Different methodologies utilized to design PDCs along with imaging characteristics and their applicability in a wide range of diseases, have been summarized in this article.

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Implantable Polymeric Drug Delivery Devices: Classification, Manufacture, Materials, and Clinical Applications

Polymers ◽

10.3390/polym10121379 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1379 ◽

Cited By ~ 48

Author(s):

Sarah Stewart ◽

Juan Domínguez-Robles ◽

Ryan Donnelly ◽

Eneko Larrañeta

Keyword(s):

Drug Delivery ◽

Side Effects ◽

Patient Compliance ◽

Oral Delivery ◽

Oral Route ◽

Clinical Applications ◽

Drug Concentrations ◽

Effective Delivery ◽

Materials Used ◽

Drug Delivery Devices

The oral route is a popular and convenient means of drug delivery. However, despite its advantages, it also has challenges. Many drugs are not suitable for oral delivery due to: first pass metabolism; less than ideal properties; and side-effects of treatment. Additionally, oral delivery relies heavily on patient compliance. Implantable drug delivery devices are an alternative system that can achieve effective delivery with lower drug concentrations, and as a result, minimise side-effects whilst increasing patient compliance. This article gives an overview of classification of these drug delivery devices; the mechanism of drug release; the materials used for manufacture; the various methods of manufacture; and examples of clinical applications of implantable drug delivery devices.

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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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NON INVASIVE DELIVERY OF PROTEIN AND PEPTIDE DRUGS: A REVIEW

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i8.18274 ◽

2017 ◽

Vol 10 (8) ◽

pp. 25 ◽

Cited By ~ 1

Author(s):

P.k. Lakshmi ◽

D Prasanthi ◽

B Veeresh

Keyword(s):

Drug Delivery ◽

Drug Transport ◽

Local Treatment ◽

Oral Formulation ◽

Systemic Delivery ◽

Peptide Drugs ◽

Administration Routes ◽

Treatment Regimens ◽

Non Invasive ◽

Proteins And Peptides

Till recent, injections remained the most common route for administration of protein and peptide drugs because of their poor bioavailability in the other routes. Because it is generally recognized that injection based delivery is a major impediment to the commercial success of therapeutic proteins and peptides, research in both academia and industry continues to focus on ways to overcome this problem. Possible non-parenteral administration routes for delivery of peptide and protein drugs include oral, nasal, ocular, transdermal, rectal, colonic, and vaginal route. The large surface area associated with most of these routes makes them attractive targets for drug delivery. While non-invasive administration by these routes is considered a more logical and achievable option for local treatment regimens, systemic delivery of proteins and peptides is significantly more challenging. In spite of effort made on the development of drugs for these routes, most of the successes fail to address how the technology will be transformed to a commercial product. The only notable exceptions have been the successful commercialization of nasal formulations for systemic delivery of a limited number of therapeutic peptides, and recent regulatory approvals of both pulmonary and buccal delivery systems for systemic delivery of insulin and an oral formulation of a small peptide analog, cyclosporine, have been commercialized. The present review aims to discuss the potential non-invasive routes of protein and peptide drug delivery. The factors which will affect drug transport and the bioavailability of proteins administered through these routes is also emphasized

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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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Medical Use of Nanoparticles

International Journal of Green Nanotechnology ◽

10.1177/1943089213506978 ◽

2013 ◽

Vol 1 ◽

pp. 194308921350697 ◽

Cited By ~ 9

Author(s):

Parva Nasimi ◽

Maryam Haidari

Keyword(s):

Drug Delivery ◽

Side Effects ◽

Human Activity ◽

The Body ◽

Size Dependent ◽

Early Stages

Researchers today are able to encapsulate medicine in nanoparticles, the size of viruses. The nanoparticles are effective for drug delivery—the delivery of the medicine to the body—because they can very precisely find diseased cells and carry the medicine to them. This means that one can suffice with less dosage and thereby fewer side effects. In addition, nanoscience and nanotechnological methods are spurring the development of more sophisticated tools for detecting diseases, such as cancer and atherosclerosis, at early stages and performing neurosurgery. Applications of nanotechnology in disease diagnoses are developing rapidly. Their unique size-dependent properties make these materials superior and indispensable in many areas of human activity.

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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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Gel-Based Materials for Ophthalmic Drug Delivery

Gels ◽

10.3390/gels7030130 ◽

2021 ◽

Vol 7 (3) ◽

pp. 130

Author(s):

Roberta Cassano ◽

Maria Luisa Di Gioia ◽

Sonia Trombino

Keyword(s):

Drug Delivery ◽

Side Effects ◽

Contact Lenses ◽

Prolonged Release ◽

Eye Drops ◽

Non Invasive ◽

Ophthalmic Drug Delivery ◽

Ophthalmic Drug ◽

In Situ Gelling

The most common route of administration of ophthalmic drugs is the topical route because it is convenient, non-invasive, and accessible to all patients. Unfortunately, drugs administered topically are not able to reach effective concentrations. Moreover, their bioavailability must be improved to decrease the frequency of administrations and their side effects, and to increase their therapeutic efficiency. For this purpose, in recent decades, particular attention has been given to the possibility of developing prolonged-release forms that are able to increase the precorneal residence time and decrease the loss of the drug due to tearing. Among these forms, gel-based materials have been studied as an ideal delivery system because they are an extremely versatile class with numerous prospective applications in ophthalmology. These materials are used in gel eye drops, in situ gelling formulations, intravitreal injections, and therapeutic contact lenses. This review is intended to describe gel-based materials and their main applications in ophthalmology.

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