New and novel approaches for enhancing the oral absorption and bioavailability of protein and peptides therapeutics

2020 ◽  
Vol 11 (11) ◽  
pp. 713-732
Author(s):  
Abhishek Kanugo ◽  
Ambikanandan Misra
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Oral Delivery ◽  
Oral Absorption ◽  
Enzyme Inhibitors ◽  
Oral Route ◽  
Limited Success ◽  
Physical Chemical ◽  
Novel Approaches ◽  
Active Research

The advancement of the oral route for macromolecules has gained a lot of attention due to its noninvasive nature, safe and challenging in active research but with limited success. Oral administration poses challenges due to poor solubility, short half-life, quick elimination and the physical, chemical and biological barriers of the gastrointestinal tract. Approaches of past for improving oral absorption, such as enhancers, mucoadhesive delivery and enzyme inhibitors have been taken over by novel approaches like advanced liposomes, self-nanoemulsifying drug delivery system, nanoparticles and targeted delivery. Eudratech™ Pep, Peptelligence, Rani Pill and Pharm Film are the emerging technologies for delivering oral proteins and peptide. Calcitonin, semaglutide and octreotide are the peptides available in the market for oral delivery as outcomes of these technologies.

Novel Approaches for Oral Delivery of Insulin and Current Status of Oral Insulin Products

2010 ◽  
Vol 3 (3) ◽  
pp. 1057-1064 ◽  
Author(s):  
Kinesh V P ◽  
Neelam D P ◽  
Punit B ◽  
Bhavesh S.B ◽  
Pragna K. S
Keyword(s):  
Diabetes Mellitus ◽  
Oral Delivery ◽  
Proteolytic Enzymes ◽  
Oral Route ◽  
The Body ◽  
Current Status ◽  
Intestinal Lumen ◽  
Insulin Administration ◽  
Novel Approaches ◽  
Dose Dependent

Diabetes mellitus is a serious pathologic condition that is responsible for major healthcare problems worldwide and costing billions of dollars annually. Insulin replacement therapy has been used in the clinical management of diabetes mellitus for more than 84 years. The present mode of insulin administration is by the subcutaneous route through which insulin is presented to the body in a non-physiological manner having many challenges. Hence novel approaches for insulin delivery are being explored. Challenges to oral route of insulin administration are: rapid enzymatic degradation in the stomach, inactivation and digestion by proteolytic enzymes in the intestinal lumen and poor permeability across intestinal epithelium because of its high molecular weight and lack of lipophilicity. Liposomes, microemulsions, nanocubicles, and so forth have been prepared for the oral delivery of insulin. Chitosan-coated microparticles protected insulin from the gastric environment of the body and released intestinal pH. Limitations to the delivery of insulin have not resulted in fruitful results to date and there is still a need to prepare newer delivery systems, which can produce dose-dependent and reproducible effects, in addition to increased bioavailability.

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

Polymers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1379 ◽  
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.

Nanocargos: A Burgeoning Quest in Cancer Management

2020 ◽  
Vol 10 (2) ◽  
pp. 149-163
Author(s):  
Atul Jain ◽  
Teenu Sharma ◽  
Sumant Saini ◽  
Om Prakash Katare ◽  
Vandana. Soni ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Oral Delivery ◽  
Imaging Techniques ◽  
Intestinal Barrier ◽  
Oral Route ◽  
In Vitro Models ◽  
In Vitro Toxicity ◽  
Cancer Management ◽  
Surface Modified

Cancer, a complex series of diseased conditions, contributes to a significant health problem and is a leading cause of mortalities across the world. Lately, with the advent of improved diagnostics and imaging techniques, and newer advanced oral chemotherapeutics; millions of cancer affected people can lengthen their life span. Despite all the challenges associated with an active chemotherapeutic molecule like microenvironment and the intestinal barrier of the gastrointestinal tract (GIT) etc., the oral delivery remains the most acceptable route of drug administration. In this regard, nanotechnology has played a significant role in the counteracting the challenges encountered with newly developed molecules and aiding in improving their bioavailability and targetability to the tumour site, while administering through the oral route. Several literature instances document the usage of nanostructured drug delivery systems such as lipid-based, polymerbased or metallic nanomaterials to improve the efficacy of chemotherapy. Besides, sitespecific targeted surface-modified drug delivery system designed to deliver the active molecule has opened up to the newer avenues of nanotechnology. However, the issue of potential toxicity allied with nanotechnology cannot be compromised and thus, needs specific ethical regulations and guidelines. The various in vitro models have been developed to evaluate the in vitro toxicity profile which can be further correlated with the invivo model. Thus, this review provides a summarized account of the various aspects related to the role of nanotechnology in cancer therapy and various related issues thereof; that must be triumphed over to apprehend its full promise.

scholarly journals Polymeric micelles for oral drug delivery: Why and how

2004 ◽  
Vol 76 (7-8) ◽  
pp. 1321-1335 ◽  
Author(s):  
M. F. Francis ◽  
Mariana Cristea ◽  
F. M. Winnik
Keyword(s):  
Drug Delivery ◽  
Oral Delivery ◽  
Oral Absorption ◽  
Polymeric Micelles ◽  
Oral Drug Delivery ◽  
Polymeric Micelle ◽  
Water Soluble ◽  
Oral Drug ◽  
Therapeutic Effects ◽  
The Impact

The oral delivery of drugs is regarded as the optimal means for achieving therapeutic effects owing to increased patient compliance. Unfortunately, the oral delivery route is beset with problems such as gastrointestinal (GI) destruction of labile molecules, low levels of macromolecular absorption, etc. To reduce the impact of digestive enzymes and to ensure the absorption of bioactive agents in an unaltered form, molecules may be incorporated into microparticulate carriers. Many approaches to achieve the oral absorption of a wide variety of drugs are currently under investigation. Among the different polymer-based drug delivery systems, polymeric micelles represent a promising delivery vehicle especially intended for poorly water-soluble pharmaceutical active ingredients in order to improve their oral bioavailability. Recent findings of a dextran-based polymeric micelle study for solubilization of a highly lipophilic drug, cyclosporin A (CsA), will be discussed.

Engineered Site-specific Vesicular Systems for Colonic Delivery: Trends and Implications

2020 ◽  
Vol 26 (42) ◽  
pp. 5441-5455
Author(s):  
Honey Goel ◽  
Karan Razdan ◽  
Richu Singla ◽  
Sushama Talegaonkar ◽  
Rajneet Kaur Khurana ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Targeted Delivery ◽  
Oral Delivery ◽  
Low Cost ◽  
Lipid Vesicles ◽  
Oral Route ◽  
Peptidase Activity ◽  
Colonic Delivery ◽  
Site Specific ◽  
Drug Degradation

Steering drug-loaded, site-specific, coated lipid vesicles to the target receptor sites have the potential of plummeting adverse effects and improving the pharmacological response in diverse pathologies of the large bowel, especially the colon. Colonic delivery via oral route has its own challenges, often governed by several glitches such as drug degradation or absorption in the upper GIT, instability of proteins/peptides due to high molecular weight, and peptidase activity in the stomach. Consequently, colon-specific coated liposomal systems (CSLS) offer a potential alternate for not only site-specificity, but protection from proteolytic activity, and prolonged residence time for greater systemic bioavailability. On the other hand, liposomal delivery via the oral route is also cumbersome owing to several barriers such as instability in GIT, difficulty in crossing membranes, and issues related to production at the pilot scale. New advancements in the field of CSLS have successfully improved the stability and permeability of liposomes for oral delivery via modulating the compositions of lipid bilayers, adding polymers or ligands. Despite this ostensible propitiousness, no commercial oral CSLS has advanced from bench to bedside for targeted delivery to the colon as yet. Nevertheless, CSLS has quite fascinated the manufacturers owing to its potential industrial viability, simplistic and low-cost design. Hence, this review aims to decipher the convolutions involved in the engineering process of industrially viable CSLS for colonic delivery.

Oral delivery of liraglutide-loaded Poly-N-(2-hydroxypropyl) methacrylamide/chitosan nanoparticles: Preparation, characterization, and pharmacokinetics

2020 ◽  
pp. 088532822094788
Author(s):  
Yanan Shi ◽  
Miaomiao Yin ◽  
Yina Song ◽  
Tengteng Wang ◽  
Shiqi Guo ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Oral Absorption ◽  
Chitosan Nanoparticles ◽  
Relative Bioavailability ◽  
Oral Route ◽  
Significant Challenge ◽  
Imaging Results ◽  
Hydroxypropyl Methacrylamide ◽  
Carrier Materials

The delivery of peptides or protein drugs via the oral route has always presented a significant challenge. Here, nanoparticles for the oral delivery of liraglutide are prepared. The nanoparticles are composed of the biodegradable carrier materials chitosan and poly-N-(2-hydroxypropyl) methacrylamide (pHPMA). In addition, CSKSSDYQC (CSK) and hemagglutinin-2 (HA2) are introduced into the particles to improve the in vivo bioavailability of liraglutide. The size of the nanoparticles is less than 200 nm, and the encapsulation efficiency is approximately 80%. Compared with the subcutaneously injected liraglutide solution group (100%), the relative bioavailability of the nanoparticle group modified with CSK and HA2 reached 10.12%, which is 2.53 times that of the oral liraglutide solution group. In vivo imaging results showed that pHPMA/HA2-CSK chitosan nanoparticles (pHPMA/HA-CCNPs) are retained in the gastrointestinal tract for up to 12 h, which is beneficial for oral absorption. CSK and HA2 modified pHPMA/chitosan nanoparticles significantly improved liraglutide oral bioavailability and therefore have the potential to be applied for oral administration of peptides and proteins.

Polymer-Lipid Hybrid Systems: Scope of Intravenous-To-Oral Switch in Cancer Chemotherapy

2020 ◽  
Vol 10 (2) ◽  
pp. 164-177 ◽  
Author(s):  
Md. Rizwanullah ◽  
Javed Ahmad ◽  
Saima Amin ◽  
Awanish Mishra ◽  
Mohammad Ruhal Ain ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Hybrid Systems ◽  
Patient Compliance ◽  
Cancer Chemotherapy ◽  
Oral Delivery ◽  
Oral Absorption ◽  
Oral Drug Delivery ◽  
Drug Carriers ◽  
Oral Drug ◽  
Oral Switch

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.

Lipid Nanocarriers for Oral Delivery of Serenoa repens CO2 Extract: A Study of Microemulsion and Self-Microemulsifying Drug Delivery Systems

Planta Medica ◽  
2018 ◽  
Vol 84 (09/10) ◽  
pp. 736-742 ◽  
Author(s):  
Clizia Guccione ◽  
Maria Bergonzi ◽  
Khaled Awada ◽  
Vieri Piazzini ◽  
Anna Bilia
Keyword(s):  
Drug Delivery ◽  
Oral Delivery ◽  
Drug Delivery Systems ◽  
Oral Absorption ◽  
Delivery Systems ◽  
Array Detector ◽  
Serenoa Repens ◽  
Lipid Nanocarriers

AbstractThe aim of this study was the development and characterization of lipid nanocarriers using food grade components for oral delivery of Serenoa repens CO2 extract, namely microemulsions (MEs) and self-microemulsifying drug delivery systems (SMEDDSs) to improve the oral absorption. A commercial blend (CB) containing 320 of S. repens CO2 extract plus the aqueous soluble extracts of nettle root and pineapple stem was formulated in two MEs and two SMEDDSs. The optimized ME loaded with the CB (CBM2) had a very low content of water (only 17.3%). The drug delivery systems were characterized by dynamic light scattering, transmission electron microscopy, and high-performance liquid chromatography (HPLC) with a diode-array detector analyses in order to evaluate the size, the homogeneity, the morphology, and the encapsulation efficiency. β-carotene was selected as marker for the quantitative HPLC analysis. Additionally, physical and chemical stabilities were acceptable during 3 wk at 4 °C. Stability of these nanocarriers in simulated stomach and intestinal conditions was proved. Finally, the improvement of oral absorption of S. repens was studied in vitro using parallel artificial membrane permeability assay. An enhancement of oral permeation was found in both CBM2 and CBS2 nanoformulations comparing with the CB and S. repens CO2 extract. The best performance was obtained by the CBM2 nanoformulation (~ 17%) predicting a 30 – 70% passive oral human absorption in vivo.

scholarly journals Current State-of-Art and New Trends on Lipid Nanoparticles (SLN and NLC) for Oral Drug Delivery

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Patrícia Severino ◽  
Tatiana Andreani ◽  
Ana Sofia Macedo ◽  
Joana F. Fangueiro ◽  
Maria Helena A. Santana ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Oral Delivery ◽  
Oral Drug Delivery ◽  
Lipid Nanoparticles ◽  
Oral Route ◽  
Delivery Systems ◽  
Oral Drug ◽  
Pharmacokinetic Parameters ◽  
Drug Molecules ◽  
Current State

Lipids and lipid nanoparticles are extensively employed as oral-delivery systems for drugs and other active ingredients. These have been exploited for many features in the field of pharmaceutical technology. Lipids usually enhance drug absorption in the gastrointestinal tract (GIT), and when formulated as nanoparticles, these molecules improve mucosal adhesion due to small particle size and increasing their GIT residence time. In addition, lipid nanoparticles may also protect the loaded drugs from chemical and enzymatic degradation and gradually release drug molecules from the lipid matrix into blood, resulting in improved therapeutic profiles compared to free drug. Therefore, due to their physiological and biodegradable properties, lipid molecules may decrease adverse side effects and chronic toxicity of the drug-delivery systems when compared to other of polymeric nature. This paper highlights the importance of lipid nanoparticles to modify the release profile and the pharmacokinetic parameters of drugs when administrated through oral route.

scholarly journals Preparation andIn VitroRelease of Drug-Loaded Microparticles for Oral Delivery Using Wholegrain Sorghum Kafirin Protein

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Esther T. L. Lau ◽  
Stuart K. Johnson ◽  
Roger A. Stanley ◽  
Deirdre Mikkelsen ◽  
Zhongxiang Fang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Gastrointestinal Tract ◽  
Drug Delivery System ◽  
Delivery System ◽  
Targeted Delivery ◽  
Oral Delivery ◽  
Protein Digestibility ◽  
Target Area ◽  
Sorghum Grains

Kafirin microparticles have been proposed as an oral nutraceutical and drug delivery system. This study investigates microparticles formed with kafirin extracted from white and raw versus cooked red sorghum grains as an oral delivery system. Targeted delivery to the colon would be beneficial for medication such as prednisolone, which is used in the management of inflammatory bowel disease. Therefore, prednisolone was loaded into microparticles of kafirin from the different sources using phase separation. Differences were observed in the protein content,in vitroprotein digestibility, and protein electrophoretic profile of the various sources of sorghum grains, kafirin extracts, and kafirin microparticles. For all of the formulations, the majority of the loaded prednisolone was not released inin vitroconditions simulating the upper gastrointestinal tract, indicating that most of the encapsulated drug could reach the target area of the lower gastrointestinal tract. This suggests that these kafirin microparticles may have potential as a colon-targeted nutraceutical and drug delivery system.

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