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•Type 2 diabetes mellitus (T2DM) is a metabolic disorder sparked by insulin resistance and dysfunction of the β cells.•Monotherapy and combinatorial drug therapies represents the ...first line treatment choices for the said disorder.•Nanotechnology based approaches offers promising potential in terms of therapeutic efficacy and improved quality of life in patients.•A plethora of nanotools have proven to be promising drug carriers for treatment of T2DM.•The present article presents an overview of the conventional treatment modalities and recent advances in the nano based drug delivery approaches for the treatment of type II DM.
Diabetes mellitus (DM) is a metabolic disorder that occurs in the body because of decreased insulin activity and/or insulin secretion. Pathological changes such as nephropathy, retinopathy, and cardiovascular complications inevitably occur in the body with the progression of the disease. DM is mainly categorized into 2 sub-types, type I DM and type II DM. While type I DM is generally treated through insulin replacement therapy, type II DM is treated with oral hypoglycaemics. The major drug therapy for type II DM comprises of insulin secretagogues, biguanides, insulin sensitizers, alpha glucosidase inhibitors, incretin mimetics, amylin antagonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors. Dual drug therapies are often recommended in patients who are unable to achieve therapeutic goals with first line oral hypoglycaemic agents as monotherapy. Inspite of the appreciable therapeutic benefits, the conventional dosage forms depicts differential bioavailability and short half-life, mandating frequent dosage and causing greater side effects leading to therapy ineffectiveness and patient non-compliance. Given the pathological complexity of the said disease, nanotechnology-based approaches are more enticing as it comes with added advantage of site-specific drug delivery with higher bioavailability and reduced dosage regimen.
In the present review article, we have made an attempt to explore the pathophysiology of type II DM, the conventional treatment approaches (mono and combination therapy) as well as the nano based drug delivery approaches for the treatment of type II DM.
•Mucoadhesive beads of metformin HCl was developed by response surface methodology.•These beads were made of ispaghula husk mucilage-gellan gum polymer-blend.•The in vitro drug release was prolonged ...over 10h and showed zero-order kinetics.•Optimized beads exhibited pH-dependent swelling and good mucoadhesivity.•These beads showed significant antidiabetic effect over 10h in diabetic rats.
Response surface methodology based on 32 factorial design was used to develop ispaghula (Plantago ovata F.) husk mucilage (IHM)-gellan gum (GG) mucoadhesive beads containing metformin HCl through Ca2+-ion cross-linked ionotropic-gelation technique for the use in oral drug delivery. GG to IHM ratio and cross-linker (CaCl2) concentration were investigated as independent variables. Drug encapsulation efficiency (DEE, %) and cumulative drug release after 10h (R10h, %) were analyzed as dependent variables. The optimized mucoadhesive beads (F-O) showed DEE of 94.24±4.18%, R10h of 59.13±2.27%. These beads were also characterized by SEM and FTIR analyses. The in vitro drug release from these beads showed controlled-release (zero-order) pattern with super case-II transport mechanism over 10h. The optimized beads showed pH-dependent swelling and good mucoadhesivity with the goat intestinal mucosa. The optimized IHM-GG mucoadhesive beads containing metformin HCl exhibited significant antidiabetic effect in alloxan-induced diabetic rats over 10h.
•Ionotropically-gelled mucoadhesive beads of metformin HCl was developed.•These beads were made of fenugreek seed mucilage-gellan gum polymer-blend.•The in vitro drug release was prolonged over 10h ...and showed zero-order kinetics.•Optimized beads exhibited pH-dependent swelling and good bioadhesion.•These beads proved prolonged and significant hypoglycemic effect in diabetic rats.
Fenugreek (Trigonella foenum-graecum L.) seed mucilage (FSM)-gellan gum (GG) mucoadhesive beads containing metformin HCl for oral use were developed through ionotropic-gelation technique. Effects of GG to FSM ratio and cross-linker (CaCl2) concentration on the drug encapsulation efficiency (DEE, %), and cumulative drug release after 10h (R10h, %) of ionotropically-gelled FSM-GG mucoadhesive beads containing metformin HCl were optimized by 32 factorial design. The optimized mucoadhesive beads showed DEE of 92.53±3.85% and R10h of 55.28±1.58% and mean diameter of 1.62±0.22mm. The in vitro metformin HCl release from these ionotropically-gelled FSM-GG beads was prolonged over 10h and followed zero-order model with super case-II transport mechanism. The optimized mucoadhesive beads also exhibited pH-dependent swelling, good mucoadhesivity with biological mucosal membrane and significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration.
•Novel mucoadhesive beads of metformin HCl was developed and optimized.•Low methoxy (LM) pectin-tamarind seed polysaccharide polymer-blend was used.•The in vitro drug release followed zero-order with ...super case-II transport mechanism.•The optimized beads showed pH-sensitive swelling and good mucoadhesive property.•These beads proved prolonged and significant hypoglycemic effect in diabetic rats.
Novel mucoadhesive beads containing metformin HCl made of low methoxy (LM) pectin-tamarind seed polysaccharide (TSP) polymer-blend was developed through ionotropic-gelation technique and optimized using 32 factorial design. Effects of LM pectin and TSP amounts on drug encapsulation efficiency (DEE), and cumulative drug release at 10h (R10h) were analyzed using response surface methodology. The optimized calcium pectinate-TSP beads containing metformin HCl showed DEE of 95.12±4.26%, R10h of 46.53±3.28%, and mean diameter of 1.93±0.26mm. The in vitro drug release from these beads was followed controlled-release (zero-order) pattern with super case-II transport mechanism. These beads were also characterized by SEM and FTIR. The optimized beads also exhibited pH-dependent swelling, good mucoadhesivity with goat intestinal mucosa and significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration.
•Ionically-gelled mucoadhesive beads of metformin HCl was developed and optimized.•These beads were made of tamarind seed polysaccharide–gellan gum polymer-blend.•The in vitro drug release showed ...zero-order with super case-II transport mechanism.•Optimized beads exhibited good mucoadhesivity with the biological mucous membrane.•These beads proved prolonged and significant hypoglycemic effect in diabetic rats.
The paper describes the development, optimization and evaluation of tamarind seed polysaccharide (TSP)-blended gellan gum (GG) mucoadhesive beads containing metformin HCl through Ca2+-ion cross-linked ionic gelation for oral drug delivery. Effects of GG to TSP ratio and cross-linker (CaCl2) concentration on the drug encapsulation efficiency (DEE, %), and cumulative drug release after 10h (R10h, %) of TSP–GG mucoadhesive beads containing metformin HCl were optimized by 32 factorial design. The optimized mucoadhesive beads (F-O) showed DEE of 95.73±4.02%, R10h of 61.22±3.44% and mean diameter of 1.70±0.24mm.These beads were characterized by SEM and FTIR analyses. The in vitro drug release from these beads showed controlled-release (zero-order) pattern over a period of 10h.The optimized TSP–GG mucoadhesive beads also exhibited pH-dependent swelling, good mucoadhesivity with biological mucosal membrane and significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration.
•New ionically gelled mucoadhesive beads of metformin HCl was developed and optimized.•Pectin and fenugreek seed mucilage were used as polymer-blends.•These beads showed pH-sensitive swelling and ...good mucoadhesive property.•The in vitro drug release followed zero order with super case-II transport mechanism.•The optimized mucoadhesive beads proved prolonged hypoglycemic effect in diabetic rats.
Calcium pectinate-fenugreek seed mucilage (FSM) mucoadhesive beads containing metformin HCl was developed through ionic-gelation. Effects of pectin and FSM amounts on drug encapsulation efficiency (DEE) and cumulative drug release at 10h (R10h) were optimized using 32 factorial design. The DEE (%) was within the range of 63.16±2.88 to 96.03±4.67% (w/w). The in vitro drug release from these beads (56.64±1.47 to 93.63±4.52% over 10h) was followed controlled-release (zero-order) pattern (R2=0.993 to 0.997) with super case-II transport mechanism. The average size of beads was within 1.47±0.14 to 2.08±0.18mm. The beads were also characterized by SEM and FTIR. The swelling and mucoadhesivity of these beads were influenced by pH of the medium. The optimized beads also exhibited good mucoadhesivity and significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration.
Exosomes are nanovesicles (30-120 nm) of endosomal origin. These exosomes contain various functional proteins and RNAs that could be used for therapeutic purposes. Currently, having a standard method ...for exosome isolation retaining its biological properties with increased yield and purity is a major challenge. The most commonly used method is differential ultracentrifugation but it has its own disadvantages, which include high time consumption, low yield due to disruption of exosome integrity, and high protein contaminants. In this study, we have identified an improved method addressing these problems for exosome isolation using ultracentrifugation since it is cost-effective and used worldwide.
We have compared differential ultracentrifugation with the modified method called one-step sucrose cushion ultracentrifugation for exosome isolation. The conditioned serum-free media from human mesenchymal stem cells cultured for 48 h was collected for exosome isolation. The cellular debris was removed by centrifugation at 300g for 10 min, followed by centrifugation at 10,000g for 30 min to remove microvesicles. Equal volumes of pre-processed conditioned media were used for exosome isolation by direct ultracentrifugation and one-step sucrose cushion ultracentrifugation. The exosomes isolated using these methods were characterized for their size, morphology, concentration, and surface marker protein expression.
It was observed that the recovery of exosomes with cup-shaped morphology from one-step sucrose cushion ultracentrifugation was comparatively high as estimated by nanoparticle tracking analysis and electron microscopy. These results were confirmed by Western blotting and flow cytometry.
We conclude that this one-step sucrose cushion ultracentrifugation method provides an effective and reproducible potential standard method which could be used for various starting materials for isolating exosomes. We believe that this method will have a wide application in the field of extracellular vesicle research where exosome isolation with high yield and purity is an imperative step. Schematic representation of comparison of UC and SUC exosome isolation methods for tissue-specific human mesenchymal stem cells. The SUC isolation method yields a greater number of cup-shaped exosomes with a relatively homogenous population for mass-scale production of exosomes for downstream analysis.
SUC One-step sucrose cushion ultracentrifugation, UC Direct ultracentrifugation.
Herein, we report the synthesis and characterization of gelatin/κ-carrageenan crosslinked polyacrylic acid hydrogel (GT-CAG-cl-polyAA) and graphene oxide incorporated hydrogel nanocomposite (GOHNC) ...through a free radical crosslinking pathway. Under optimized reaction conditions, GT-CAG-cl-polyAA displayed 486 % maximum swelling percentage. TEM image depicted wrinkled silk veil wave-type surface morphology of graphene oxide (GO), whereas, the SEM analysis indicated the porous nature of the GT-CAG-cl-polyAA and GOHNC capable of accumulating a large number of water/dye molecules. GT-CAG-cl-polyAA exhibited 96.11 % and 82.16 % dye removal potential for the adsorption of methylene blue (MB) and coomassie brilliant blue (CB), respectively under optimized conditions. GOHNC enhanced the % dye removal efficiency (98.39 % for MB and 94.50 % for CB). The maximum adsorption capacity of GOHNC for the removal of CB and MB was 312.7 mg/g and 94.9 mg/g, respectively. The adsorption of CB and MB exhibited best fitting with Flory-Huggins adsorption isotherms data. The negative values of ΔG° and positive values of ΔS° which were obtained from the adsorption isotherm plot suggested the thermodynamic feasibility of the adsorption. Also, the samples were reusable for up to five consecutive cycles without any degradation and hence suggested a considerable pathway for the separation of textile dyes.
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•Environmentally benign fabrication of graphene oxide based hydrogel nanocomposite•Efficient removal of MB (Xe = 312.7 mg/g) and CB (Xe = 94.9 mg/g)•Higher dye removal efficiency than many of the existing adsorbents•The synthesized samples were recyclable upto five consecutive cycles.
•Alprazolam-loaded nanoparticles for oral use were prepared by heat coagulation.•Chitosan, egg albumin and PEG 400 were used as excipients.•Among them, highest drug entrapment was found ...99.37±4.86%.•The highest drug entrapped nanoparticles showed average particle size of 259.60nm.•The in vitro drug release showed sustained drug release over 24h.
The possibility of inter-polymeric complexation of cationic chitosan and anionic egg albumin stabilized with PEG 400 to develop novel nanoparticles for oral delivery of alprazolam by heat coagulation method at pH 5.4 and 80°C. Nine formulations were prepared by changing the concentration of chitosan, PEG 400 and heating time. The alprazolam entrapment efficiency of these nanoparticles was in the range of 68.12±1.27 to 99.37±4.86%. These nanoparticles were characterized by FTIR, DSC, P-XRD and FE-SEM analysis. Average particle diameter, poly-dispersity index and zeta potential of these nanoparticles were found 259.60nm, 0.501, and −9.00mV, respectively. The in vitro drug release from these alprazolam-loaded nanoparticles showed sustained drug release over a period of 24h. In conclusion, these newly developed chitosan-egg albumin-PEG nanoparticles were found to be a promising vehicle for sustained release delivery of lipophilic drugs.
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