scholarly journals Nanoparticulate Drug Delivery Strategies to Address Intestinal Cytochrome P450 CYP3A4 Metabolism towards Personalized Medicine

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1261
Author(s):  
Rui Xue Zhang ◽  
Ken Dong ◽  
Zhigao Wang ◽  
Ruimin Miao ◽  
Weijia Lu ◽  
...  

Drug dosing in clinical practice, which determines optimal efficacy, toxicity or ineffectiveness, is critical to patients’ outcomes. However, many orally administered therapeutic drugs are susceptible to biotransformation by a group of important oxidative enzymes, known as cytochrome P450s (CYPs). In particular, CYP3A4 is a low specificity isoenzyme of the CYPs family, which contributes to the metabolism of approximately 50% of all marketed drugs. Induction or inhibition of CYP3A4 activity results in the varied oral bioavailability and unwanted drug-drug, drug-food, and drug-herb interactions. This review explores the need for addressing intestinal CYP3A4 metabolism and investigates the opportunities to incorporate lipid-based oral drug delivery to enable precise dosing. A variety of lipid- and lipid-polymer hybrid-nanoparticles are highlighted to improve drug bioavailability. These drug carriers are designed to target different intestinal regions, including (1) local saturation or inhibition of CYP3A4 activity at duodenum and proximal jejunum; (2) CYP3A4 bypass via lymphatic absorption; (3) pH-responsive drug release or vitamin-B12 targeted cellular uptake in the distal intestine. Exploitation of lipidic nanosystems not only revives drugs removed from clinical practice due to serious drug-drug interactions, but also provide alternative approaches to reduce pharmacokinetic variability.

Nanoscale ◽  
2017 ◽  
Vol 9 (40) ◽  
pp. 15252-15277 ◽  
Author(s):  
Justyna Florek ◽  
Romain Caillard ◽  
Freddy Kleitz

Mesoporous silica nanocarriers are discussed as potential oral drug delivery systems, focusing on their advantages and limitations, and future perspectives.


1970 ◽  
Vol 7 (5) ◽  
pp. 65-73
Author(s):  
Saloni Jain ◽  
Rahul Ancheriya ◽  
S Srivastva ◽  
Shankar Lal Soni ◽  
Mukesh Sharma

Novel drug delivery systems (NDDS) are one of the most strategies which enable to overcome the problems related to drug bioavailability. It is the rate and extent to which a drug becomes available to the target tissue after its administration. Over the last century, phyto-chemical science and phyto-pharmacological science established numerous plant compounds with various biological activities and health promoting benefits such as anti-mutagenicity, anti-carcinogenicity and anti-oxidative activity, for age-related diseases namely memory loss, osteoporosis, diabetic wounds, immune and liver disorders, etc. Herbal medicines have been known since eons for their safety, efficacy, folk acceptability and fewer side effects.  


2021 ◽  
Vol 18 ◽  
Author(s):  
Yrysbaeva Aidana ◽  
Yibin Wang ◽  
Jie Li ◽  
Shuyue Chang ◽  
Ke Wang ◽  
...  

Background: Electrospinning is developing rapidly from an earlier laboratory method into an industrial process. The clinical applications are approached in various ways through electrospun medicated nanofibers. The fast-dissolving oral drug delivery system (DDS) among them is one of the most promising routes in the near future for commercial applications. Methods: Related papers are investigated, including the latest research results, on electrospun nanofiber-based fast-dissolution DDSs. Results: Several relative topics have been concluded: 1) the development of electrospinning, ranging from 1-fluid blending to multi-fluid process and potential applications in the formation of medicated nanofibers involving poorly water-soluble drugs; 2) Selection of appropriate polymer matrices and drug carriers for filament formation; 3) Types of poorly water-soluble drugs ideal for fast oral delivery; 4) The methods for evaluating fast-dissolving nanofibers; 5) The mechanisms that promote the fast dissolution of poorly water-soluble drugs by electrospun nanofibers; 6) the important issues for further development of electrospun medicated nanofibers as oral fast-dissolving drug delivery systems. Conclusions & Perspectives: The unique properties of electrospun-medicated nanofibers can be used as oral fast dissolving DDSs of poorly water-soluble drugs. However, some significant issues need to be investigated, such as scalable productions and solid dosage form conversions.


Author(s):  
Sunandita Sarker ◽  
Ryan Jones ◽  
Gabriel Chow ◽  
Benjamin Terry

Abstract Despite being the preferred route of drug administration, the oral formulation of biological drugs is limited due to its intrinsic instability, low permeability, and physical, chemical and immunological barriers. Various innovative swallowable technologies such as drug-loaded, dissolvable microneedles, mucoadhesive patches, and various microdevices present unique drug-carrying capabilities. The current work presents a novel soft stent platform that can facilitate contact between the small intestine tissue and drug carriers to enhance drug absorption and increase residence time. This study aims to prove the concept of this novel platform and determine if the soft stent will retain orally to the ileocecal valve longer than a capsule-shaped bolus. Benchtop studies on an intestinal simulator showed successful retention of the soft stent compared to a control capsule. In vivo studies in pig models also showed that the soft stent was retained longer than the control capsule. Overall, this study shows promise that this novel platform could be used for oral drug delivery of biologics.


2021 ◽  
Vol 11 (2-S) ◽  
pp. 156-161
Author(s):  
Hans Raj ◽  
Shagun Sharma ◽  
Ankita Sharma ◽  
Kapil Kumar Verma ◽  
Amit Chaudhary

Microspheres are multiparticulate drug delivery systems that are designed to deliver drugs to a particular location at a fixed rate. Microspheres are free-flowing powders made up of biodegradable proteins or synthetic polymers with particle sizes ranging from 1 to 1000µm. Benefits of the use of microspheres in fields such as drug delivery, bone tissue manufacturing, and the absorption and desorption of contaminants by regeneration. The study shows the method of planning and measurement of microsphere parameters. Microspheres are complex, such as bioadhesive microspheres, polymeric microspheres, magnetic microspheres, floating microspheres, radioactive microspheres. Microspheres may be used in various fields such as cosmetics, oral drug delivery, target drug delivery, ophthalmic drug delivery, gene delivery, and others listed in the study. In order to achieve optimal therapeutic effectiveness, it is important to deliver the agent to the target tissue at an optimum level within the right timeframe, resulting in little toxicity and minimal side effects. There are different approaches to supplying the medicinal drug to the target site in a continuous managed manner. One such strategy is the use of microspheres as drug carriers. In this article, the value of the microsphere is seen as a novel drug delivery carrier to achieve site-specific drug delivery was discussed. Keywords: microspheres, method of preparations, polymer, bioadhesion, types of microspheres


2021 ◽  
Vol 12 ◽  
Author(s):  
Mohammed S. Alqahtani ◽  
Mohsin Kazi ◽  
Mohammad A. Alsenaidy ◽  
Muhammad Z. Ahmad

The oral route is the most common route for drug administration. It is the most preferred route, due to its advantages, such as non-invasiveness, patient compliance and convenience of drug administration. Various factors govern oral drug absorption including drug solubility, mucosal permeability, and stability in the gastrointestinal tract environment. Attempts to overcome these factors have focused on understanding the physicochemical, biochemical, metabolic and biological barriers which limit the overall drug bioavailability. Different pharmaceutical technologies and drug delivery systems including nanocarriers, micelles, cyclodextrins and lipid-based carriers have been explored to enhance oral drug absorption. To this end, this review will discuss the physiological, and pharmaceutical barriers influencing drug bioavailability for the oral route of administration, as well as the conventional and novel drug delivery strategies. The challenges and development aspects of pediatric formulations will also be addressed.


2020 ◽  
Vol 10 (2) ◽  
pp. 164-177 ◽  
Author(s):  
Md. Rizwanullah ◽  
Javed Ahmad ◽  
Saima Amin ◽  
Awanish Mishra ◽  
Mohammad Ruhal Ain ◽  
...  

Cancer chemotherapeutic administration by oral route has the potential to create “hospitalization free chemotherapy”. Such a therapeutic approach will improve patient compliance and significantly reduce the cost of treatment. In current clinical practice, chemotherapy is primarily carried out by intravenous injection or infusion and leads to various unwanted effects. Despite the presence of oral delivery challenges like poor aqueous solubility, low permeability, drug stability and substrate for multidrug efflux transporter, cancer chemotherapy delivery through oral administration has gained much attention recently due to having more patient compliance compared to the intravenous mode of administration. In order to address the multifaceted oral drug delivery challenges, a hybrid delivery system is conceptualized to merge the benefits of both polymeric and lipid-based drug carriers. Polymer-lipid hybrid systems have presented various significant benefits as an efficient carrier to facilitate oral drug delivery by surmounting the different associated obstacles. This carrier system has been found suitable to overcome the numerous oral absorption hindrances and facilitate the intravenous-to-oral switch in cancer chemotherapy. In this review, we aimed to discuss the different biopharmaceutic challenges in oral delivery of cancer chemotherapy and how this hybrid system may provide solutions to such challenges.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 887
Author(s):  
Nutthapoom Pathomthongtaweechai ◽  
Chatchai Muanprasat

The small intestine provides the major site for the absorption of numerous orally administered drugs. However, before reaching to the systemic circulation to exert beneficial pharmacological activities, the oral drug delivery is hindered by poor absorption/metabolic instability of the drugs in gastrointestinal (GI) tract and the presence of the mucus layer overlying intestinal epithelium. Therefore, a polymeric drug delivery system has emerged as a robust approach to enhance oral drug bioavailability and intestinal drug absorption. Chitosan, a cationic polymer derived from chitin, and its derivatives have received remarkable attention to serve as a promising drug carrier, chiefly owing to their versatile, biocompatible, biodegradable, and non-toxic properties. Several types of chitosan-based drug delivery systems have been developed, including chemical modification, conjugates, capsules, and hybrids. They have been shown to be effective in improving intestinal assimilation of several types of drugs, e.g., antidiabetic, anticancer, antimicrobial, and anti-inflammatory drugs. In this review, the physiological challenges affecting intestinal drug absorption and the effects of chitosan on those parameters impacting on oral bioavailability are summarized. More appreciably, types of chitosan-based nanomaterials enhancing intestinal drug absorption and their mechanisms, as well as potential applications in diabetes, cancers, infections, and inflammation, are highlighted. The future perspective of chitosan applications is also discussed.


2014 ◽  
Vol 2 (02) ◽  
pp. 130-143 ◽  
Author(s):  
Hema Jaiswal

Over the recent past, many of the research groups are focusing their research on this technology. Amongst Oral drug delivery system Oral Strip Technology (OST) is gaining much attention. The advantages of OST are the administration to pediatric and geriatric patient population where the difficulty of swallowing larger oral dosage forms is eliminated. This technology has been used for local action, rapid release products and for buccoadhesive systems that are retained in the oral cavity to release drug in controlled fashion. OST offers an alternate platform for molecules that undergo first pass metabolism and for delivery of peptides. An ideal OST should have the following properties: high stability, transportability, ease of handling and administration, no special packaging material and/or processing requirements, no water necessary for application, and a pleasant taste. All these requirement are fulfilled by the oral films. The OST is a good tool for product life cycle management for increasing the patent life of existing molecules or products. Compared to some of the complicated and expensive process (like lyophilization) used to manufacture ODTs(Orally Disintegrating Tablets), the OST is relatively easy to fabricate,thus reducing the overall cost of the therapy. One of the reasons is that the buccal mucosa is less permeable and is thus not able to elicit a rapid onset of absorption and hence better suited for formulations that are intended for sustained release action. Further, the buccal mucosa being relatively immobile mucosa and readily accessible, it makes it more advantageous for retentive systems used for oral trans mucosal drug delivery. The primary disadvantage associated with buccal delivery route is the low flux that in turn results in low drug bioavailability. To overcome this hurdle, various buccal penetration enhancers have been studied which improve the absorption pattern of the molecules. The article shows OST encompassing materials used in OST, method of preparation, evaluation, applications, commercial technologies and future Business prospects of this technology.


2013 ◽  
Vol 24 ◽  
pp. 107-122
Author(s):  
Nimish Shah ◽  
R.K. Mewada ◽  
Tejal Mehta

Chitosan is a modified form of Chitin. It is a modified carbohydrate polymer derived by hydrolyzing the aminoacetyl groups of chitin. Chitosan is a biodegradable natural polymer which is, biocompatible, non-toxic. It also shows anti-bacterial properties. This polysaccharide is available in different forms such as nanoparticles, solution, powder, flake, fiber, film, etc. Due to its wide range of physical forms and good reactivity with other compounds, chitosan can produce various blends. Nanoparticles of various natural biopolymers have emerged as potential carrier for drugs in oral controlled drug delivery. Nanostructured drug carriers allow the delivery of not only small-molecule drugs but also of nucleic acids and proteins. Chemical modification of nanoparticles of chitosan is useful for the association of bioactive molecules to polymer and controlling the drug release profile. In recent years focus on chitosan is shifted to its derivatives. This versatile material has broad applications in many different fields. Various physical forms of chitosan and its blends together with other derivatives such as composites and graft copolymers have been developed to overcome limitations of different polymeric materials such as poor mechanical properties and to improve its functionality towards specific applications. Nanoparticles of chitosan and it derivatives are extensively exploited in the field of oral drug delivery. The progress made in converting chitosan and its blends into nanoparticles forms as well as the preparation methods are studied. For preparation of these blends and nanoparticles of chitosan need to be dissolved in for reactions. We also studied its dissolution behavior with different acids. It shows quite interesting results.


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