Self-regulated glycosylated insulin delivery

doi:10.1016/0168-3659(90)90132-D

Journal of Controlled Release

Volume 11, Issues 1–3, January 1990, Pages 193-201

https://doi.org/10.1016/0168-3659(90)90132-D Get rights and content

Abstract

A self-regulating insulin delivery system, based on the concept of competitive binding between synthetic glycosylated insulin (G-insulin) and glucose to concanavalin A (Con A) ligand substrate, has been designed. The competitive binding of the two ligands for the substrate regulates G-insulin release in relation to the outside glucose concentration, while a polymeric membrane, serving as a peritoneal implant pouch containing G-insulin and Con A, is used to control the permeability of glucose influx and G-insulin efflux. Mono-, di- and tri-sugar substituted insulins have been characterized. The nonimmunogenicity, bioactivity and pharmacodynamic activity of succinyl amidophenyl glucopyranoside insulin (SAPG-insulin) and succinyl amidophenyl mannopyranoside insulin (SAPM-insulin) were found to be comparable to unsubstituted bovine insulin. Initial systems were based on SAPG- or SAPM-insulin with water soluble Con A tetramer contained in pouches of porous ρ-HEMA or cellulose acetate. A second system was designed with Con A immobilized beads (to prevent Con A leakage) and cellulose acetate or Nucleopore^® membranes. A new system was designed by crosslinking the Con A molecules to create a gel and enclosing the insulin and gel in a pouch of Durapore^® membrane (heat sealable and having comparable permeability to G-insulins andglucose). The fabricated pouch in vitro showed a short lag time in response to glucose with no leakage of Con A molecules. An alternative system of Con A and SAPG-insulin loaded into microcapsules demonstrated a short lag time for insulin release due to the large surface area of the microcapsules.

References (25)

HellerJ.
Chemically self-regulated drug delivery systems
J. Controlled Release
(1988)
IwataH. et al.
Preparation and properties of novel environment-sensitive membranes prepared by graft polymerization onto a porous membrane
J. Membrane Sci.
(1988)
SunA.M. et al.
Microencapsulation of living cells — A long term delivery system
J. Controlled Release
(1985)
SeftonM.V. et al.
Hydrophilic polyacrylates for the microencapsulation of fibroblasts or pancreatic islets
J. Controlled Release
(1987)
SeminoffL.A. et al.
A self-regulating insulin delivery system. I. Characterization of a synthetic glycosylated insulin derivative
Int. J. Pharm.
(1989)
SeminoffL.A. et al.
A self-regulating insulin delivery system. II. In vivo characteristics of glcyosylated insulin
Int. J. Pharm.
(1989)
SchadeD.S. et al.
Normalization of plasma insulin profiles in diabetic subjects with programmed insulin delivery
Diabetes Care
(1980)
RuppW.M. et al.
The use of an implantable insulin pump in the treatment of Type II diabetes
N. Engl. J. Med.
(1982)
ShichiriM. et al.
The development of wearabletype artificial endocrine pancreas and its usefulness in glycemic control of human diabetes mellitus
Biomed. Biochim. Acta
(1984)
PietriA. et al.
Cutaneous complications of chronic continuous subcutaneous insulin infusion therapy
Diabetes Care
(1981)

AbelP. et al.

Experience with an implantable glucose sensor as a prerequisite of an artificial beta cell

Biomed. Biochim. Acta

(1984)

LangerR. et al.

Controlled release and magnetically modulated systems for macromolecules

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Conventional drug delivery system generally deals with the issues involving repeated dosing and systemic toxicities. Since few decades, hydrogels have played a significant role as a carrier in drug delivery to minimize the drawbacks pertaining to conventional drug delivery. They.
have been considered as one of the most reliable groups of biomaterials due to their biocompatibility, physicochemical properties, and designed interaction with living surroundings. The diversity and versatility of hydrogels make them extraordinary not only in the field of targeted drug delivery but also in tissue engineering, fabrication of contact lenses, and wound dressings. Another reason which makes hydrogels a smart carrier in drug delivery is their special characteristic to retain water inside their network. In recent years, hydrogels fabricated from natural, semi-synthetic, and synthetic polymers have gained a lot of attention in targeted drug delivery of therapeutic agents for the management of cancer, gastric ulcers, brain tumors, diabetes, bacterial infections, etc. Also, with their tremendous capability to modify, hydrogels proved to be a promising vehicle for drug delivery in cosmetological and dermatological conditions. The motive behind this review is to highlight the key concept of hydrogels, their fabrication methods, stimuli-responsive polymers used for their fabrication, and their diverse utilization in the delivery system. Further, different completed and ongoing clinical trials of hydrogel-based drugs have also been discussed. Suitable studies are provided from the literature that supports the tremendous utilization of hydrogels in different segments and how they are modified suitably in several ways to achieve desired targeted delivery of therapeutic agents.
DFT study of therapeutic potential of graphitic carbon nitride (g-C<inf>3</inf>N<inf>4</inf>) as a new drug delivery system for carboplatin to treat cancer
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Chemotherapy is a medicinal type of curing treatment in which chemotherapeutic agents; “drugs” are used to treat or kill the cancer cells. But it also represented the severe cytotoxic side effects [8], recurrence of the tumor because the drugs are not properly released to a specific cite. Furthermore, cancer cells become resistant to many drugs which is also a big obstacle in successful chemo-therapy [9].
DFT studies were performed to evaluate the chemotherapeutic potential of g-C₃N₄ as a drug carrier for carboplatin in cancer treatment. The optimized, electronic and excited-state characteristics of g-C₃N₄, carboplatin, and g-C₃N₄-carboplatin-complex were determined to evaluate the targeted drug delivery ability of g-C₃N₄. The E_ad values of g-C₃N₄-carboplatin-complex for the gas phase is −1.39 eV and in the water phase is −0.52 eV. The non-covalent-interaction (NCI) plot revealed that weak forces of interaction are present between g-C₃N₄ and carboplatin. These weak forces of interactions are responsible for an obvious offloading of the drug from g-C₃N₄ carrier at its targeted site. Through frontier molecular orbital analysis it was evaluated that during excitation carboplatin behaves as HOMO and delivers the charge towards the LUMO i.e. g-C₃N₄. Charge-decomposition-analysis (CDA) was also performed to further support the charge transfer process which interprets the maximum overlap between the orbitals of the carboplatin and g-C₃N₄. In the gas phase, the λ_max of g-C₃N₄- carboplatin-complex is red-shifted by 74 nm. While in the aqueous phase the λ_max is blue-shifted. These theoretically obtained spectra are also in good consistency with that of experimental spectra. The PET (photo-induced electron-transfer) process, as well as electron–hole-theory, were also performed for the graphical elucidation of different excited-states. The photo-induced-electron-transfer (PET) process interprets that upon interaction quenching in fluorescence takes place. Furthermore, g-C₃N₄ with cationic (+1) and anionic (−1) charge-state (g-C₃N₄^+1/−1) represented negligible distortion in structure and forms stable-complexes with carboplatin. All the observed results confirmed that g-C₃N₄ possesses significant chemo-therapeutic potential as a drug carrier for carboplatin in cancer treatment. This theoretical work will also stimulate the concern of researchers for further exploration of other 2D nanomaterials for drug-delivery applications.
Can nanoparticles and nano‒protein interactions bring a bright future for insulin delivery?
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Under the high glucose conditions, glucose competed for the binding sites on Con A with glycosylated insulin, resulting in the release of insulin in proportion to the glucose level. In further studies, the formulation was optimized with Con A derivatives (e.g., PEGylation Con A67), glycosylated insulin (e.g., succinyl amidophenyl mannopyranoside insulin68,69) or glycosylpoly(ethylene glycol) insulin70 to improve the stability and insulin release. GBP-based mechanism is generally used for developing glucose-responsive hydrogels71–73.
Insulin therapy plays an essential role in the treatment of diabetes mellitus. However, frequent injections required to effectively control the glycemic levels lead to substantial inconvenience and low patient compliance. In order to improve insulin delivery, many efforts have been made, such as developing the nanoparticles (NPs)-based release systems and oral insulin. Although some improvements have been achieved, the ultimate results are still unsatisfying and none of insulin-loaded NPs systems have been approved for clinical use so far. Recently, nano‒protein interactions and protein corona formation have drawn much attention due to their negative influence on the in vivo fate of NPs systems. As the other side of a coin, such interactions can also be used for constructing advanced drug delivery systems. Herein, we aim to provide an insight into the advance and flaws of various NPs-based insulin delivery systems. Particularly, an interesting discussion on nano‒protein interactions and its potentials for developing novel insulin delivery systems is initiated.
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It is well known that hydrogels show remarkable potential for many applications, such as drug delivery vehicles (Hoare & Kohane, 2008; Liu, Wang, Ju, Xie, & Chu, 2010), tissue engineering scaffold (Seliktar, 2012; Stuart et al., 2010), smart sensors/actuators (Ma, Guo, & Anderson, 2013; Yao et al., 2015), “on/off” switches (He et al., 2012; Shastri et al., 2015), artificial muscles (Iamsaard et al., 2014; Islam, Li, Smyth, & Serpe, 2013) and chem/bioseparation platforms (Nagase, Kobayashi, & Okano, 2009; Ozay et al., 2010). Among the stimuli-responsive hydrogels, sugar responsive hydrogels are of particular interest (Kim et al., 1990), because the sugars are the most important biological structure composition and the main source of energy. The sugars, including sugar, glycoprotein, nucleoside, RNA etc., are important intermediate metabolites and information media material for cell recognitions and signal transmission.
Novel intelligent cellulose/4-vinyl-phenylboronic acid (VPBA) composite bio-hydrogels with glucose and pH-responsiveness were successfully prepared via electron beam irradiation technology at room temperature. The composites were characterized by Fourier transform infrared spectrum (FT-IR) and X-ray photoelectron spectroscopy (XPS). The electron beam irradiation results in the appearance of carbonyl in the polymerization of 4-ethenyl-phenylboronic acid, grafting and cross linking reaction in composites, and a novel composite hydrogel was formed between the poly-4-ethenyl-phenylboronic acid and cellulose matrix. By means of the incorporation of phenylboronic acid groups, the composite hydrogels with pH and glucose responsive properties was produced, and glucose responsive properties were investigated by the self-regulation of insulin release of composite hydrogel through a serial glucose solution with different concentrations, which is having great potential applications in many fields.
Programmable hydrogels
2018, Biomaterials
Programmable hydrogels are defined as hydrogels that are able to change their properties and functions periodically, reversibly and/or sequentially on demand. They are different from those responsive hydrogels whose changes are passive or cannot be stopped or reversed once started and vice versa. The purpose of this review is to summarize major progress in developing programmable hydrogels from the viewpoints of principles, functions and biomedical applications. The principles are first introduced in three categories including biological, chemical and physical stimulation. With the stimulation, programmable hydrogels can undergo functional changes in dimension, mechanical support, cell attachment and molecular sequestration, which are introduced in the middle of this review. The last section is focused on the introduction and discussion of four biomedical applications including mechanistic studies in mechanobiology, tissue engineering, cell separation and protein delivery.
Glucose-responsive insulin release: Analysis of mechanisms, formulations, and evaluation criteria
2017, Journal of Controlled Release
Diabetes mellitus has become one of the biggest medical challenges affecting millions of people globally. Alternative treatments for diabetes are currently being intensively investigated to improve the treatment efficacy and life qualities for diabetic patients. Glucose-responsive insulin release (GRIR) systems have exhibited tremendous potential to improve the normal glycemic control and to reduce the incidence of hyperglycemia and hypoglycemia, which further reduces potential complications in diabetic patients. In a given GRIR drug formulation, accuracy, response time, and reversibility of the GRIR functions are three key features enabling potential seamless control of blood glucose level. Nevertheless, there is significant challenge preventing current GRIR formulations from achieving them. This review article analyzes the most updated literature and provides insights on the impact of GRIR mechanisms, and formulations on these key features, and the relevant in vitro and in vivo evaluation methods to test these functions.

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: Paper presented at the Fourth International Symposium on Recent Advances in Drug Delivery Systems, Salt Lake City, UT, U.S.A., February 21–24, 1989.

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Journal of Controlled Release

Abstract

References (25)

Chemically self-regulated drug delivery systems

J. Controlled Release

Preparation and properties of novel environment-sensitive membranes prepared by graft polymerization onto a porous membrane

J. Membrane Sci.

Microencapsulation of living cells — A long term delivery system

J. Controlled Release

Hydrophilic polyacrylates for the microencapsulation of fibroblasts or pancreatic islets

J. Controlled Release

A self-regulating insulin delivery system. I. Characterization of a synthetic glycosylated insulin derivative

Int. J. Pharm.

A self-regulating insulin delivery system. II. In vivo characteristics of glcyosylated insulin

Int. J. Pharm.

Normalization of plasma insulin profiles in diabetic subjects with programmed insulin delivery

Diabetes Care

The use of an implantable insulin pump in the treatment of Type II diabetes

N. Engl. J. Med.

The development of wearabletype artificial endocrine pancreas and its usefulness in glycemic control of human diabetes mellitus

Biomed. Biochim. Acta

Cutaneous complications of chronic continuous subcutaneous insulin infusion therapy

Diabetes Care

Experience with an implantable glucose sensor as a prerequisite of an artificial beta cell

Biomed. Biochim. Acta

Controlled release and magnetically modulated systems for macromolecules

Cited by (110)

Biomedical applications of hydrogels in drug delivery system: An update

DFT study of therapeutic potential of graphitic carbon nitride (g-C<inf>3</inf>N<inf>4</inf>) as a new drug delivery system for carboplatin to treat cancer

Can nanoparticles and nano‒protein interactions bring a bright future for insulin delivery?

The preparations of novel cellulose/phenylboronic acid composite intelligent bio-hydrogel and its glucose, pH-responsive behaviors

Programmable hydrogels

Glucose-responsive insulin release: Analysis of mechanisms, formulations, and evaluation criteria