Insulin Encapsulation Efficiency Research Articles

Oral Delivery of Insulin from Trimethyl Chitosan/Tragacanth: In Vitro, MTT, and In Vivo Bioactivity Tests

: Insulin-loaded Trimethyl Chitosan (TMC)/tragacanth microspheres were prepared by microemulsion dispersion and triggered in situ gelation. Microspheres were characterized by their mean size and distribution by laser diffraction spectroscopy and Brunauer-Emmet-Teller theory. Insulin encapsulation efficiency and in vitro release were determined by Bradford protein assay, and bioactivity was assessed in vitro using an enzyme-linked immunoassay diagnostic kit and in vivo using Wistar diabetic rats. TMC/tragacanth particles suppressed insulin release in acidic media and promoted a sustained release at near-neutral conditions. Micro-capsulated insulin was bioactive, demonstrated by both in vivo and in vitro bioassays.

Injectable nanosized formulation for glucose-responsive insulin delivery

Glucose-responsive insulin (GRI) can tremendously facilitate insulin administration via expanding the safe dosage window and reducing injection frequency, as well as enhancing blood glucose control via actively adjusting the insulin release rate. We have previously prepared a robust ion complex-based GRI for type 1 diabetes treatment; however, this complex precipitates easily, which could cause difficulty of injection and inaccuracy of dosage. It remains elusive whether nanoparticulation of this complex could increase suspension stability and retain glucose responsiveness. Herein, we have linked poly (ethylene glycol) (PEG) to 4-carboxy-3-fluorophenylboronic acid (FPBA)-modified poly-ʟ-lysine to obtain PEG-PLL-FPBA. PEG-PLL-FPBA and insulin can form nanosized insulin complex (NIC) with a high insulin loading content and encapsulation efficiency. Of note, the size of the prepared NIC can keep stable for more than 7 days. The NIC showed glucose-stimulated insulin release in vitro with a maximal glucose-responsive index of 400 %. In a streptozotocin (STZ)-induced type 1 diabetic mouse model, the subcutaneously injected NIC could normalize hyperglycemia in 30 min and maintain it normally for 20 h, while minimal toxicity has been identified.

Insulin-Loaded Soybean Trypsin Inhibitor-Chitosan Nanoparticles: Preparation, Characterization, and Protective Effect Evaluation.

The aim of this work was to prepare insulin-loaded nanoparticles using soybean trypsin inhibitor (STI) and chitosan (CS) as a potential coating. The nanoparticles were prepared by complex coacervation, and characterized for their particle size, polydispersity index (PDI), and encapsulation efficiency. In addition, the insulin release and enzymatic degradation of nanoparticles in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were evaluated. The results showed that the optimal conditions for preparing insulin-loaded soybean trypsin inhibitor-chitosan (INs-STI-CS) nanoparticles were as follows: CS concentration of 2.0 mg/mL, STI concentration of 1.0 mg/mL, and pH 6.0. The INs-STI-CS nanoparticles prepared at this condition had a high insulin encapsulation efficiency of 85.07%, the particle diameter size was 350 ± 5 nm, and the PDI value was 0.13. The results of the in vitro evaluation of simulated gastrointestinal digestion showed that the prepared nanoparticles could improve the stability of insulin in the gastrointestinal tract. Compared with free insulin, the insulin loaded in INs-STI-CS nanoparticles was retained at 27.71% after 10 h of digestion in the intestinal tract, while free insulin was completely digested. These findings will provide a theoretical basis for improving the stability of oral insulin in the gastrointestinal tract.

THE ELECTROSPRAYED INSULIN-LOADED POLYCAPROLACTONE MICROPARTICLES AS A DRUG CARRIER

Drug and protein encapsulated polymeric microparticles have been considered as the most effective delivery in pharmaceutical biotechnology. In this work, we report the fabrication of polycaprolactone microparticles (PCL MPs) containing insulin via an electrospraying method. The morphology, chemical composition, physicochemical properties, insulin encapsulation and release efficiency, degradation of PCL MPs, and cytotoxicity are systematically characterized and analyzed. The results indicate that insulin do not incorporate with PCL matrix leading to the deformation of PCL MPs’ structure. In addition, insulin can be loaded into the PCL MPs with high concentration up to 25 % while it remains chemical properties when releasing from the PCL MPs. Moreover, insulin demonstrates high burst release within the first day, subsequently the release become more stable during 2-7 days. The 80% viability of the cell suggests that PCL MPs are biocompartible to cells. As a consequence, the above mentioned material is proved to be has high potential for insulin carrier in controlled release application

Synthesis and testing of polymer grafted mesoporous silica as glucose-responsive insulin release drug delivery systems

Stimuli-responsive materials based on mesoporous silica have been widely studied for the controlled release of drugs. Glucose-responsive systems play a vital role in the controlled release of insulin because they can smartly adjust the amount of released insulin in response to the fluctuational blood glucose concentration. Here, the mesoporous silica (MS) was modified with 3-fluoro-4-carboxyphenylboronic acid (FCPBA) to prepare phenylboronic acid-modified mesoporous silica (MS-FCPBA). N-acryloyl glucosamine (AGA) was copolymerized with N-isopropyl acrylamide (NIPAM) and acrylic acid (AAc) respectively to synthesize two polymers with diol groups, noted as P(NIPAM-co-AGA) and P(AAc-co-AGA) respectively. Since the phenylboronic acid group can form a borate ester bond with the diol group, the polymers were coated on the surface of insulin-loaded MS-FCPBA to obtain the insulin release systems. The results showed that the loading capacity and encapsulation efficiency of insulin could reach 14.7% and 85.9%, respectively. The two systems exhibited different glucose-responsive performance.

A new Glucose-Responsive delivery system based on Sulfonamide-phenylboronic acid for subcutaneous insulin injection

A novel glucose- and temperature-responsive random copolymer, poly sulfonamide-phenylboronic acid-co-N-vinylcaprolactam p(SAPBA-co-NVCL), was synthesised via the “one-pot” method. After the polymer was made into nanoparticles, their properties, including insulin loading capacity and encapsulation efficiency, were investigated; their cytotoxicity and treatment effectiveness were also explored. Thermogravimetric results confirmed that p(SAPBA-co-NVCL) had high stability. Performance test results showed that p(SAPBA-co-NVCL) nanoparticles had round morphology and good glucose sensitivity under physiological conditions. Concurrently, we found that the size of the nanoparticles and the amount of insulin released increased significantly with the increase of glucose concentration. In addition, cytotoxicity results suggested that p(SAPBA-co-NVCL) nanoparticles were non-toxic to normal cells, but had a certain lethality effect on tumour cells. Animal experiments showed that p(SAPBA-co-NVCL) nanoparticles stably lowered blood sugar within 12 h. Moreover, they did not cause toxic damage to the tissue; however, there was a small amount of bleeding at the injection site. In conclusion, our results suggested that p(SAPBA-co-NVCL) nanoparticles are safe and can be used for the subcutaneous injection of insulin or other hypoglycaemic proteins.

Preparation of Polylactic Acid/Glycolic Acid Copolymer Nanoparticles and Its Effect in the Treatment of Diabetes

Insulin (INS) is easily degraded when administered orally and loading it into polylactic acid/glycolic acid (PLGA) polymer nanoparticles can enhance the efficacy of the drug. The W/O/W double emulsion solvent volatilization method was adopted to prepare INS-loaded PLGA nanoparticles. The preparation formula of nanoparticles was determined according to the type, concentration, and PLGA concentration of the emulsifier. Then, the morphology, particle size, and drug encapsulation efficiency of nanoparticles were characterized. Phosphate buffered solution (PBS) with pH = 7.4 was utilized as the release medium, and the prepared nanoparticles were analyzed for in vitro release performance. In addition, the rat diabetes model was constructed, and subcutaneous injection of nanoparticle in vitro release solution was performed to observe its hypoglycemic effect, which was used for the treatment of diabetic patients. Patients were rolled into experimental group and control group. The changes of the patients’ HbA1c, blood lipids (total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)), C peptide, and aminopeptidase N (APN) were observed before and after treatment. Through the test, the appearance of the prepared nanoparticles was round, the average particle size was 416.7 nm, and the INS encapsulation efficiency was (36.82±2.26)%. After 36 h, the cumulative release of INS reached (60.58 ±1.45)%, and then the release rate gradually slowed down. The drug release tended to be balanced after 72 h, and the best hypoglycemic effect was achieved after subcutaneous administration 3 h (P < 0.01). The blood glucose level of the rat diabetes model was greatly decreased after 3 h injection of 36.8 IU/kg PLGA polymer nanoparticles (P < 0.05), and the blood glucose dropped to the lowest at 8 h (P < 0.01), which was only (38.8 ± 3.72)% of the initial blood glucose. HbA1C of diabetic patients increased remarkably after treatment (P < 0.05), TG, TC, and LDL-C in blood lipids decreased, and HDL-C increased, without statistically considerable differences (P > 0.05). The serum APN level increased greatly (P < 0.01). In short, the prepared PLGA polymer nanoparticles can effectively reduce blood glucose, help diabetic patients to relieve the toxicity of high glucose in the body, and improve the secretion function of INS.

Preparation of snail cyst and PEG-4000 composite carriers via PEGylation for oral delivery of insulin: An in vitro and in vivo evaluation

Purpose: To develop PEGylated mucin as a carrier system for oral insulin delivery.
 Methods: Varied ratios of snail cyst were molecularly modified with polyethylene glycol 4000 (PEG 4000). Briefly, In each case, 20 g quantities of snail cyst and PEG 4000 were separately dispersed in distilled water, stirred and allowed to stand for 24 h to produce a homogeneous dispersion and clear solution, respectively. The solution of PEG was added to the snail cyst dispersion, stirred and allowed 12 h for molecular interaction. The mixture was added to a 250-mL beaker containing 100 mL of light liquid paraffin. The microparticles were obtained after stirring and removing the paraffin using chilled acetone. The obtained PEGylated mucin matrices, which were subsequently loaded with insulin using a diffusion method, characterized for particles size, drug loading, encapsulation efficiency, in vitro drug release and evaluated for oral application in diabetic rats.
 Results: The polymer hybrids improved insulin encapsulation efficiency (max 82.3 %), gave. polydispersity indices that ranged from 0.11 ± 0.1 to 0.24 ± 0.2, zeta potential values between 28 ± 0.3 and 38 ± 1.1 mV. Insulin release was highest (68 % in 6 h) for batch C and was sustained for 10 h in simulated intestinal fluid. The optimized batch (C-5) showed higher hypoglycaemic activity (56.5 %) than control (0.5 %) in diabetic rats.
 Conclusion: The results suggest that PEGylated mucin can potentially be developed as a platform for oral insulin delivery

Novel porous starch/alginate hydrogels for controlled insulin release with dual response to pH and amylase.

An important principle in the development of oral insulin is to protect insulin from the harsh conditions of the stomach and release it in a controlled manner in the intestine. In the present study, novel insulin-loaded porous starch-alginate hydrogel systems (In-S-Alg) including In-MS-Alg (prepared with porous maize starch), In-WS-Alg (porous waxy maize starch), and In-RS-Alg (porous rice starch) were successfully developed. As a representative, In-MS-Alg was further coated with gelatinized-retrograded high amylose maize starch (HA) films with different thicknesses to prepare In-MS-HA/Alg hydrogel beads for improving the functionality of controlled release of insulin under the action of α-amylase. The In-S-Alg and In-MS-HA/Alg hydrogel beads were evaluated in terms of structural and morphological properties, encapsulation effect on insulin as well as its release behavior. The results show that insulin was distributed in the pores and cavities of porous starch granules. In In-MS-HA/Alg hydrogel beads, insulin was increasingly blocked inside porous starch with the increased thickness of the HA film. Encapsulation efficiency of insulin in all In-S-Alg and In-MS-HA/Alg hydrogel beads was >80%. Amazingly, both the hydrogel beads successfully achieved the goal of triggered release upon pH changes and α-amylase addition. Most of the insulin (about 90%) was retained in the simulated gastric fluid; while the release rate of insulin in the simulated intestinal fluid increased gradually, and was further accelerated in the presence of α-amylase. Furthermore, for the In-MS-HA/Alg hydrogel beads, the insulin release rate can be gradually reduced by increasing the thickness of the HA film, which provided the possibility to match the rate of increase of the blood glucose level after the intake of food with different glycemic indices. Therefore, the novel hydrogel prepared in this study may be a promising and safe delivery carrier for oral insulin.

Sterculia striata gum as a potential oral delivery system for protein drugs

Natural polysaccharides have been investigated as vehicles for oral insulin administration. Because of their non-toxic, renewable, low cost and readily available properties, gums find multiple applications in the pharmaceutical industry. This work aimed to develop a Sterculia striata gum-based formulation associated with additional biopolymers (dextran sulfate, chitosan, and albumin), a crosslinking agent (calcium chloride) and stabilizing agents (polyethylene glycol and poloxamer 188), to increase the oral bioavailability of proteins. Insulin was used as a model drug and the methods used to prepare the formulation were based on ionotropic pregelation followed by electrolytic complexation of oppositely charged biopolymers under controlled pH conditions. The developed formulation was characterized to validate its efficacy, by the determination of its average particle size (622 nm), the insulin encapsulation efficiency (70%), stability in storage for 30 days, and the in vitro mucoadhesion strength (92.46 mN). Additionally, the developed formulation preserved about 64% of initial insulin dose in a simulated gastric medium. This study proposed, for the first time, a Sterculia striata gum-based insulin delivery system with potential for the oral administration of protein drugs, being considered a valid alternative for efficient delivery of those drugs.

Mucin-Grafted Polyethylene Glycol Microparticles Enable Oral Insulin Delivery for Improving Diabetic Treatment

In this study, different ratios of mucin-grafted polyethylene-glycol-based microparticles were prepared and evaluated both in vitro and in vivo as carriers for the oral delivery of insulin. Characterization measurements showed that the insulin-loaded microparticles display irregular porosity and shape. The encapsulation efficiency and loading capacity of insulin were >82% and 18%, respectively. The release of insulin varied between 68% and 92% depending on the microparticle formulation. In particular, orally administered insulin-loaded microparticles resulted in a significant fall of blood glucose levels, as compared to insulin solution. Subcutaneous administration showed a faster, albeit not sustained, glucose fall within a short time as compared to the polymeric microparticle-based formulations. These results indicate the possible oral delivery of insulin using this combination of polymers.

Dextran-crosslinked glucose responsive nanogels with a self-regulated insulin release at physiological conditions

Different glucose-responsive nanogels of N-isopropylacrylamide (NIPAM) and 4-(1,6-dioxo-2,5-diaza-7-oxamyl) phenylboronic acid (DDOPBA) were synthesized using dextran-grafted maleic acid (Dex-MA) as a crosslinker. The formed nanogels (P(NIPAM-co-Dex-co-DDOPBA)s) were verified by 1H NMR, TEM, DLS and X-ray photoelectron spectroscopy (XPS). The incorporation of DDOPBA provided a remarkable sensitivity towards glucose in physiological pH due to the existence of electron-withdrawing group in its structure. Similarly, the hydrophilic Dex-MA modulated the temperature-sensitivity near physiological temperature. The nanogels exhibited high insulin loading capacity and encapsulation efficiency and the in vitro release profiles demonstrated a glucose dependant release of the payload at physiological pH and temperature.

Prospective insulin-based ophthalmic delivery systems for the treatment of dry eye syndrome and corneal injuries

The presence of insulin (INS) receptors on the ocular surface (OS) and lacrimal gland (LG), and the high prevalence of dry eye syndrome (DES) and corneal lesions in diabetic patients suggest that INS is relevant for OS homeostasis and wound healing. The study aims at developing delivery systems for the topical administration of INS to the OS in order to improve INS local bioavailability and evaluate the influence of the delivery systems on DES in diabetic rats (DM) (n = 05/group). Chitosan microparticles (MP), chitosan/poloxamer gel (GEL) and MP-loaded GEL (GELMP), with or without INS were developed. Formulations were instilled into the eyes of diabetic rats (DM) for 15 days and the tear fluid volume, corneal cells morphology and cornea thickness were assessed and compared with an aqueous dispersion of INS (DISP-INS). All delivery systems had pH of about 6, osmolality suitable for topical application and positive zeta potential. The MPs with or without INS had sizes close to 4 μm, spherical morphology and INS encapsulation efficiency of 77 ± 6%. DISP-INS and GELMP-INS formulations produced tear secretion amounts significantly higher than those receiving formulations containing no INS and similar to healthy animals. Cornea surface impression cytology showed that treatment with INS-delivery systems and not DISP-INS almost normalized cells morphology. Treatment with GELMP-INS increased INS by 2.5 in the LG and eyeball as compared to the groups treated with GEL-INS and MP-INS, while treatment with DISP-INS left no traces of drug in the eye after treatment termination. GEL and GELMP containing INS were also able to normalize the thickness of the corneal epithelia. In conclusion, GELMP-INS normalized tear fluid volume, corneal thickness, protected corneal cells morphology and increased ocular bioavailability of INS, making it a promising treatment strategy for DES and corneal lesions.

The influence of spatial distribution on add-on therapy of designed Ca-Alg/CS MEMs system

To improve the efficacy and reduce the systemic toxicity of the diabetes mellitus, herewith, we developed a novel microparticles-embedded microcapsules (MEMs) system, synthesized from calcium alginate/chitosan (Ca-Alg/CS), by emulsion gelation using a high voltage electrostatic droplet generator. In our study, we selected two antidiabetic drugs insulin (INS) and metformin (MET) as model drugs to investigate different spatial distribution appropriate of MEMs system. Characterization based on particle size and morphology, encapsulation efficiency and drug loading, as well as drug delivery properties were carried out on the MEMs system. Typical multi-chamber structure was shown by SEM and the optical spectra. The average diameters of microparticles and Ca-Alg/CS MEMs were 2100 nm and 410 μm, respectively. Insulin and MET were embedded into MEMs via electrostatic reaction according to FT-IR spectra. Moreover, drug loading and encapsulation efficiency of INS were higher than that of MET in this system when drugs were loaded alone or together. More importantly, this system has potential for orderly drug release and well sustained release when MET in the inner and INS in the outer space could be applied as a combination therapy for diabetes. The obtained in vivo experimental data on diabetes rats has shown that the designed MEMs system resulted in a higher hypoglycemic effect within add-on therapy.

Polyurethane‐incorporated chitosan/alginate core–shell nano‐particles for controlled oral insulin delivery

ABSTRACTChitosan (CS) and polyurethane‐chitosan (PU‐CS) nano‐particles (NPs) were prepared for the core formation by complex coacervation method whereas alginate (ALG) and PU‐ALG were crosslinked by ionic gelation method to form the protective shell‐layer over the core. Effects of PU incorporation either within the core or shell or both were investigated by different in vitro and in vivo parameters. Fourier transform infrared (FTIR) spectroscopy of different compositions of nano‐particles showed distinct characteristic peaks for CS, PU, and ALG, indicating their presence in variable ratios. Significance of polyurethane‐incorporated systems towards insulin encapsulation efficiency, swelling parameters, insulin release, and in vivo pharmacological effect were also studied. Particle sizes, zeta potential, morphological analysis, mucoadhesion study, and in vivo acute toxicity studies of these core–shell nano‐particles were also performed. Bioavailability of insulin ranged from 9.04% to 11.6% for polyurethane‐incorporated chitosan‐alginate core–shell nano‐particle formulations which was significantly higher than the insulin bioavailability of basic CS/ALG core–shell nano‐particle system. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46365.

Enteric-coated insulin microparticles delivered by lipopeptides of iturin and surfactin

Surfactin, a lipopeptide produced by Bacillus species, has been used for the oral delivery of insulin. In this study, another lipopeptide of iturin was tested for its ability to orally delivery insulin alone or plus surfactin. Iturin could form co-precipitate with insulin at acidic pH values. After treatment by ultrasonification, the structure of coprecipitate was destroyed that led to a significant decrease in hypoglycemic effect after oral administration. Iturin weakly binds to (Kd = 257 μM) and induce insulin structure more compact that is favorable for insulin uptake by the intestine. After being coated with Acryl-Eze by lyophilization, the coprecipitate formed the spherical enteric-coated insulin microparticles delivered by iturin with a relative oral bioavailability of 6.84% in diabetic mice. For further improving oral hypoglycemic effect, surfactin was added to form the spherical enteric-coated insulin microparticles in a formulation containing insulin, Acryl-Eze, iturin and surfactin at a ratio of 1:1:0.5: 0.5 (w/w), with an insulin encapsulation efficiency of 66.22%. The enteric-coated insulin microparticles delivered by iturin plus surfactin showed a classical profile for controlled release in the intestine with a relative bioavailability of 7.67% after oral administration, which could effectively control the postprandial blood glucose at a level about 50% of the initial one just like the subcutaneous injection. Collectively, iturin plus surfactin is more efficient for oral delivering insulin than the sole one, and the resultant enteric-coated insulin microparticles are potential for the development of oral insulin to control postprandial blood glucose in diabetic patients.

Glucose-responsive biopolymer nanoparticles prepared by co-assembly of concanavalin A and amylopectin for insulin delivery

The development of glucose-responsive biopolymer nanocarriers for self-regulated insulin delivery is significant in the treatment of diabetes. In this work, for the first time, we have developed a new approach to prepare glucose-responsive biopolymer nanoparticles co-assembled by concanavalin A (Con A) and amylopectin. The influence of the Con A-amylopectin mass ratio, incubation time, pH, and ionic strength on the characteristics of the obtained nanoparticles was investigated. Under optimal conditions, the biopolymer nanoparticles were spherical with diameters of 100–300nm. The results of fluorimetry indicated that the conformation of Con A was changed with the combination of a different concentration of amylopectin. The Fourier transform infrared (FTIR) spectra of biopolymer nanoparticles indicated that the nanoparticles were formed through the interaction between Con A and amylopectin. Insulin could be embedded into nanoparticles, and the encapsulation efficiency of insulin was approximately 69.73%. The loading capacity of insulin was up to 17%. The insulin-release rate for nanoparticles in 3mg/ml glucose media increased 2.23 times that of nanoparticles in the absence of glucose. Thus, the developed biopolymer nanoparticles with underlying glucose-sensitive behavior are excellent candidates for treatment of diabetes.

Preparation of polyurethane–alginate/chitosan core shell nanoparticles for the purpose of oral insulin delivery

Waste polyethylene terephthalate (PET) is depolymerized through glycolysis and the glycolyzed product, bis (2-hydroxyethylene) terephthalate (BHET) is utilized in the synthesis of polyurethane as diol. Polyurethane (PU) is incorporated in a core- shell nanoparticle formulation along with alginate (ALG) and chitosan (CS) to develop an efficient oral insulin delivery vehicle. Fourier transform infrared (FT-IR) spectrums of the polyurethane-alginate/chitosan (PU-ALG/CS) nanoparticles confirm the presence of all elements distinctly. Nanoparticles of average particle size 90–110nm are clearly visible from the images of scanning electron microscope (SEM) and transmission electron microscope (TEM). Unique characteristics of insulin loaded PU-ALG/CS nanoparticles are noticed in both in vitro and in vivo studies. More than 90% insulin encapsulation efficiency, sustained swelling, controlled insulin release from mucoadhesive nanoparticle formulation are the major causes of long term hypoglycaemic effects in diabetic mice and improved insulin bioavailability (10.36%). PU-ALG/CS nanoparticles are also found to be safe, according to the acute toxicity studies.

Preparation and evaluation of insulin-loaded nanoparticles based on hydroxypropyl-β-cyclodextrin modified carboxymethyl chitosan for oral delivery

Novel insulin-loaded nanoparticles based on hydroxypropyl-β-cyclodextrin modified carboxymethyl chitosan (CMC-HP-β-CD) were prepared to improve the oral bioavailability of insulin. The CMC-HP-β-CD was characterized by FT-IR spectroscopy and 1H-NMR spectra. The insulin-loaded nanoparticles were prepared through crosslinking with calcium ions, and the morphology and size of the prepared nanoparticles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Cumulative release in vitro study was performed respectively in simulated gastric medium fluid (SGF, pH=1.2), simulated intestinal fluid (SIF, pH=6.8) and simulated colonic fluid (SCF, pH=7.4). The encapsulation efficiency of insulin was up to 87.14 ± 4.32% through high-performance liquid chromatography (HPLC). Statistics indicated that only 15% of the encapsulated insulin was released from the CMC-HP-β-CD nanoparticles in 36 h in SGF, and about 50% of the insulin could be released from the nanoparticles in SIF, whereas more than 80% was released in SCF. In addition, the solution containing insulin nanoparticles could effectively reduce the blood glucose level of diabetic mice. The cytotoxicity test showed that the samples had no cytotoxicity. CMC-HP-β-CD nanoparticles are promising candidates as potential carriers in oral insulin delivery systems.

Dextran-b-poly(lactide-co-glycolide) polymersome for oral delivery of insulin: In vitro and in vivo evaluation

Insulin is the first line therapy in type 1 diabetes and usually patients suffer from three or more daily insulin injections. It is obvious that patient compliance can be improved greatly if insulin could be formulated in an oral dosage form.In the current study, polymersomes based on amphiphilic copolymers of dextran (DEX)5000–poly(lactic-co-glycolic acid) (PLGA)13,000 and DEX25000–PLGA48000 were synthesized and used for the encapsulation of insulin. The polymersomes were prepared using a modified direct hydration method by blending an aqueous solution of insulin with DEX–PLGA copolymers at room temperature. The in vitro insulin release through the nanopolymersomal system was studied in HCl 0.1N (pH1.2) and phosphate buffered saline (pH7.4).The results demonstrated that the average insulin encapsulation efficiency was >90%. The in vitro release experiment demonstrated that while insulin release in the simulated gastric condition was negligible, a significant amount of insulin was released in the simulated intestinal condition. According to the results of a circular dichroism test, secondary and tertiary structures of the released insulin were identical to that of standard insulin.Permeability studies across MDCK cells showed that permeability levels after 240min were 16.89±0.39% with DEX5000–PLGA13000 and 9.34±0.79% with DEX25000–PLGA48000, indicating a noticeable increase compared with free insulin.Significant hypoglycemic effects in the in vivo diabetic rat model revealed the efficacy of the DEX–PLGA-based polymersomes as oral insulin carriers. Thus, insulin-loaded, self-assembled DEX–PLGA polymersomes showed promising in vitro and in vivo efficiency and can be considered as a potential oral insulin carrier system.