Nanoparticles For Oral Delivery Research Articles

Silymarin loaded solid lipid nanoparticles for oral delivery: Development, characterization and cytotoxic effect on breast cancer cells

The current study aimed to develop a silymarin (SM) loaded solid lipid nanoparticles (SLNs). Further, silymarin loaded solid lipid nanoparticles (SM-SLNs) were characterized for different quality parameters. The SLNs were prepared by temperature modulated solidification technique. The glyceryl monostearate (GMS) was selected as lipid, tween 80 as surfactant and mannitol as cryoprotectant. The SM-SLNs were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), thermal behavior, and crystallinity. Further, the formulation was elucidated by MTT assay for cytotoxicity assessment. The particle size and PDI of the optimized formulation was found to be 178.6 ± 4.32 nm and 0.146, respectively. ZP (-36.4 mV) with a negative surface charge confirmed the physical stability of SLNs. Differential scanning calorimetry (DSC), X-ray diffraction (XRD) confirmed the transformation of lipid into SLNs through polymorphic transition of lipid crystallinity from β'-modification to α-modification and conversion of crystallinity of drug to amorphous state. The optimized formulation had an EE of 79.86%. The in-vitro drug release depicted a burst release for 1 h followed by fast release for 6 h and then sustained release over a duration of 24 h. SM-SLNs significantly reduced the growth of MCF-7 cells compared to silymarin. SM-SLNs exhibited small size in nanometer with narrow distribution, physically stable, and high entrapment efficiency. The developed nanoformulation could be used as a suitable drug delivery system for silymarin that has low water solubility, and a promising candidate for development of effective formulation in cancer therapy.

Nanoparticles for oral delivery: targeted therapy for inflammatory bowel disease.

As a group of chronic and idiopathic gastrointestinal (GI) disorders, inflammatory bowel disease (IBD) is characterized by recurrent intestinal mucosal inflammation. Oral administration is critical for the treatment of IBD. Unfortunately, it is difficult to target the bowel located in the GI tract due to multiple physical barriers. The unique physicochemical properties of nanoparticle-based drug delivery systems (DDSs) and their enhanced permeability and retention effects in the inflamed bowel, render nanomedicines to be used to implement precise drug delivery at diseased sites in IBD therapy. In this review, we described the pathophysiological features of IBD, and designed strategies to exploit these features for intestinal targeting. In addition, we introduced the types of currently developed nano-targeted carriers, including synthetic nanoparticle-based and emerging naturally derived nanoparticles (e.g., extracellular vesicles and plant-derived nanoparticles). Moreover, recent developments in targeted oral nanoparticles for IBD therapy were also highlighted. Finally, we presented challenges associated with nanotechnology and potential directions for future IBD treatment.

ORAL DELIVERY OF SILVER NANOPARTICLES – A REVIEW

Silver nanoparticles (NP) offer many applications in the science and technology. Oral delivery of such tiny particles results in enhanced drug absorption, reduction in dose, and minimize adverse effects. This review focuses on the mainly on the effects in the gastrointestinal tract along with its in vitro and in vivo studies carried on the silver NP. In this review, we compiled some of the extensive research in the field of silver NP, highlighting some of the most recent trends in the area. Search was carried in English language using Science direct, PubMed, and Google scholar search engines. The effects of silver NP on gastrointestinal tract such as absorption, distribution, metabolism, and elimination were compiled in this review. In addition, selected in vitro and in vivo studies related to the same are discussed. The accumulation of silver NP leading to Arginia condition also emphasized in the study. Silver NP and herbal silver NP in oral delivery can be exploited for the further safer and effective treatment.

Preparation, Characterization and Optimization of Irbesartan Loaded Solid Lipid Nanoparticles for Oral Delivery

The purpose of this study was to develop and evaluate irbesartan (IS) loaded solid lipid nanoparticles (SLNs; IS-SLNs) that might enhance the oral bioavailability of IS. IS, an angiotensin-receptor antagonist, used to treat hypertension. However, poor aqueous solubility and poor oral bioavailability has limited therapeutic applications of IS. Components of the SLNs include either of trimyristin/tripalmitin/tristearin/trilaurate/stearic acid/beeswax, and surfactants (Poloxamer 188 and soylecithin). The IS-SLNs were prepared by hot homogenization followed by ultrasonication method and evaluated for particle size, poly dispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), drug content and in vitro drug release. The physical stability of optimized formulation was studied at refrigerated and room temperature for two months. The optimized IS-SLN formulation (F4) had a mean diameter of about 217.6±3.62 nm, PDI of 0.163±0.032, ZP of -28.5±4.12, assay of 99.8±0.51 and EE of 93.68±2.47%. The formulation showed sustained drug release compared with control formulation over 24 h. Optimized formulation was found to be stable over two months. IS-SLN showed nearly spherical in shape using and converted to amorphous form by DSC. Thus, the results conclusively demonstrated SLNs could be considered as an alternative delivery system for the oral bioavailability enhancement of IS.

Recent Advances in Oral Nano-Antibiotics for Bacterial Infection Therapy.

Bacterial infections are the main infectious diseases and cause of death worldwide. Antibiotics are used to treat various infections ranging from minor to life-threatening ones. The dominant route to administer antibiotics is through oral delivery and subsequent gastrointestinal tract (GIT) absorption. However, the delivery efficiency is limited by many factors such as low drug solubility and/or permeability, gastrointestinal instability, and low antibacterial activity. Nanotechnology has emerged as a novel and efficient tool for targeting drug delivery, and a number of promising nanotherapeutic strategies have been widely explored to overcome these obstacles. In this review, we explore published studies to provide a comprehensive understanding of the recent progress in the area of orally deliverable nano-antibiotic formulations. The first part of this article discusses the functions and underlying mechanisms by which nanomedicines increase the oral absorption of antibiotics. The second part focuses on the classification of oral nano-antibiotics and summarizes the advantages, disadvantages and applications of nanoformulations including lipid, polymer, nanosuspension, carbon nanotubes and mesoporous silica nanoparticles in oral delivery of antibiotics. Lastly, the challenges and future perspective of oral nano-antibiotics for infection disease therapy are discussed. Overall, nanomedicines designed for oral drug delivery system have demonstrated the potential for the improvement and optimization of currently available antibiotic therapies.

Mucoadhesive and pH responsive fucoidan-chitosan nanoparticles for the oral delivery of methotrexate

Considering the potential of mucoadhesive properties of nanoparticles in oral delivery, this work describes the preparation and characterization of fucoidan/chitosan nanoparticles loaded with methotrexate (MTX) intended to lung cancer therapy. The nanoparticles were produced and characterized in terms of size, surface charge, entrapment efficiency, and morphology. The size of the developed nanoparticles was around 300 nm, the zeta potential value was negative (ca. −30 mV), revealing a low tendency to aggregate. The self-assembled fucoidan/chitosan nanoparticles were stable at acidic pH (1.6–5.2), without disintegration under pH 6–7.4, revealing resistance through the gastrointestinal tract, and were found to be mucoadhesive suggesting ability to enhance drug oral bioavailability. Lung cancer cells quickly internalized the developed nanoparticles. Moreover, MTX-loaded fucoidan/chitosan nanoparticles up to 245 μg mL−1 in polymer equivalent to 23.5 μg mL−1 of MTX were safe towards fibroblasts but hampered lung cancer cell proliferation mediated by an apoptotic process. MTX-loaded nanoparticles were 7-fold more effective in inhibiting lung cancer cells proliferation than the free drug, showing the potential of fucoidan-chitosan nanoparticles to improve the cytotoxicity of free methotrexate on A549 lung cancer cells. These results also demonstrate that fucoidan/chitosan nanoparticles may provide a suitable platform for poor-water soluble compounds' oral delivery.

Application of polymeric nanoparticles in oral delivery of recombinant human erythropoietin: A review

Recombinant Human Erythropoietin drugs are known as erythropoietin stimulating agents which stimulate the bone marrow to produce more red blood cells in the body. It is used an antianemic in the treatment of renal anemia and chemotherapy induced anemia. It also use in treatment of HIV, cerebral malaria and neurological disease like schizophrenia. The recombinant human erythropoietin dosage form currently available in the market is parenteral dosage form that is ready for injection liquid vial (syringe), which is usually administered 2-3 times weekly. To achieve a therapeutic effect of parenterally administered EPO, cumulative doses are required that significantly exceed levels of endogenous EPO. These high serum levels result in prolonged circulation times of EPO and unspecific binding to non-targeted tissue, which may lead to severe undesired side effects i.e. growth of tumor and also increased risk of death. By using the nanotechnology, side effects and toxicity related to high dose of erythropoietin should be reduces and prolong drug release. this will achieve by reducing administration frequency and lowering dosage of erythropoietin.
 Keywords: Recombinant Human Erythropoietin, Nanoparticle, Prolong drug release, Anemia

Development of an Advanced Delivery System of CSKSSDYQC Peptide Modified N-Trimethyl Chitosan Nanoparticles for Oral Delivery of Gemcitabine

Development of an Advanced Delivery System of CSKSSDYQC Peptide Modified N-Trimethyl Chitosan Nanoparticles for Oral Delivery of Gemcitabine

Development and in vitro characterization of chitosan-coated polymeric nanoparticles for oral delivery and sustained release of the immunosuppressant drug mycophenolate mofetil

Objective: To develop an oral sustained release formulation of mycophenolate mofetil (MMF) for once-daily dosing, using chitosan-coated polylactic acid (PLA) or poly(lactic-co-glycolic) acid (PLGA) nanoparticles. The role of polymer molecular weight (MW) and drug to polymer ratio in encapsulation efficiency (EE) and release from the nanoparticles was explored in vitro.Methods: Nanoparticles were prepared by a single emulsion solvent evaporation method where MMF was encapsulated with PLGA or PLA at various polymer MW and drug: polymer ratios. Subsequently, chitosan was added to create coated cationic particles, also at several chitosan MW grades and drug: polymer ratios. All the formulations were evaluated for mean diameter and polydispersity, EE as well as in vitro drug release. Differential scanning calorimetry (DSC), surface morphology, and in vitro mucin binding of the nanoparticles were performed for further characterization.Results: Two lead formulations comprise MMF: high MW, PLA: medium MW chitosan 1:7:7 (w/w/w), and MMF: high MW, PLGA: high MW chitosan 1:7:7 (w/w/w), which had high EE (94.34% and 75.44%, respectively) and sustained drug release over 12 h with a minimal burst phase. DSC experiments revealed an amorphous form of MMF in the nanoparticle formulations. The surface morphology of the MMF NP showed spherical nanoparticles with minimal visible porosity. The potential for mucoadhesiveness was assessed by changes in zeta potential after incubation of the nanoparticles in mucin.Conclusion: Two chitosan-coated nanoparticles formulations of MMF had high EE and a desirable sustained drug release profile in the effort to design a once-daily dosage form for MMF.

Nanoparticles for oral delivery: Design, evaluation and state-of-the-art

The oral route is a preferred method of drug administration, though achieving effective drug delivery and minimizing off-target side effects is often challenging. Formulation into nanoparticles can improve drug stability in the harsh gastrointestinal (GI) tract environment, providing opportunities for targeting specific sites in the GI tract, increasing drug solubility and bioavailability, and providing sustained release in the GI tract. However, the unique and diverse physiology throughout the GI tract, including wide variation in pH, mucus that varies in thickness and structure, numerous cell types, and various physiological functions are both a barrier to effective delivery and an opportunity for nanoparticle design. Here, nanoparticle design aspects to improve delivery to particular sites in the GI tract are discussed. We then review new methods for evaluating oral nanoparticle formulations, including a short commentary on data interpretation and translation. Finally, the state-of-the-art in preclinical targeted nanoparticle design is reviewed.

Vitamin B12 functionalized layer by layer calcium phosphate nanoparticles: A mucoadhesive and pH responsive carrier for improved oral delivery of insulin

The present study investigates the potential of layer by layer coated calcium phosphate nanoparticles – for oral delivery of insulin where Vitamin B12 grafted chitosan and sodium alginate have been used as cationic and anionic polyelectrolyte respectively. The major emphasis has been given on the role Vitamin B12 conjugated chitosan as cationic polyelectrolyte (VitB12-Chi) in the delivery system. VitB12-Chi conjugate was prepared by carbodiimide reaction. The formulated VirB12-Chi-CPNPs were tested for in vitro and in vivo efficacy studies carried out in Caco-2 monolayers and diabetic rats. VitB12-Chi-CPNPs with particle size <250nm and zeta potential+32.56(±2.34) exhibited pH responsive insulin release at simulated gastric fluid and simulated intestinal fluid. Fluorescence microscopy and flow cytometry studies revealed higher uptake of VitB12-Chi-CPNPs in Caco-2 monolayer in comparison to Chi-CPNPs. Further reduction in TEER supported paracellular transport of insulin because of opening of tight epithelial junctions. In vivo intestinal uptake of FITC tagged Vit-B12-Chi-CPNPs from different intestinal segments supported paracellular and receptor mediated uptake of VitB12-Chi-CPNPs. Plasma insulin and blood glucose levels were measured in diabetic rats and showed about four fold increases in insulin bioavailability and sustained hypoglycemic effects up to 12h of administration with VitB12-Chi-CPNPs in comparison to Chi-CPNPs. Results of the study revealed the potential of layer by layer nanoparticles for oral insulin delivery. The study also specifically highlighted the role of VitB12 as a pH sensitive and targeting ligand which significantly participated in enhancing insulin oral bioavailability. Statement of significanceOral delivery of insulin is always the most desirable approach for diabetic patients however it’s also the most challenging in respect to formulation development due to harsh gastrointestinal conditions. Several groups have been working from decades for oral delivery of insulin. However the beauty of this prototype formulation is that it exhibits the pH responsive behavior in natural condition of gastrointestinal tract. It resists the release of insulin at gastric condition however stimulate the release at intestinal conditions. Apart from pH responsive behavior it utilizes multiple pathways to improve the overall bioavailability of insulin including paracellular transport and receptor mediated endocytosis.

Various Emerging Trends in Insulin Drug Delivery Systems

Lowering of blood glucose level in patients can be achieved by insulin therapy as it plays a key role in the control of hyperglycaemia for type 1 diabetes. Insulin delivery systems that are currently available include syringes, infusion pumps, jet injectors and pens. The tedious part for the type 1 diabetes patients is to tolerate needle after needle injections while undergoing treatment for both glucose measurement and to deliver insulin. A rigorous research effort has been undertaken worldwide to replace the authentic subcutaneous route by a more accurate and non-invasive route. The newer methods explored include the artificial pancreas with closed-loop system, transdermal insulin, and buccal, oral, pulmonary, nasal, ocular and rectal routes. The future trends include use of insulin inhalers, trandermal patches, pills, pumps etc. Some of the non-invasive delivery systems include polymeric hydrogels and insulin loaded bioadhesive poly (D,L-lactide-co-glycolide) nanoparticles for oral delivery, aerosolized liposomes with dipalmitoyl phosphatidylcholine for pulmonary delivery, β cyclodextrins for nasal delivery, microneedle arrays fabricated from hyaluronic acid and iontophoresis for trandermal delivery, chitosan-zinc-insulin complex for the controlled delivery of insulin.

Development of a poly (ɛ Caprolactone) based nanoparticles for oral delivery of Quercetin

Quercetin loaded Poly (ɛ caprolactone; PCL) nanoparticles were prepared by the solvent displacement method. The influences of formulation variables (polymer and surfactant concentration) were investigated. The results of formulations F1-F9 showed Particle size (nm) in a different medium ranged from 189.10 ± 0.28 to 252.14 ± 2.32 in 0.1 N HCl and 184.06 ± 3.84 to 288.54 ± 2.86 in phosphate buffer pH 7.4, Dissolution efficiency (%) of 46.42 ± 5.42 to 72.20 ± 0.68 and drug loading (%) of 7.18 ± 0.25 to 9.27 ± 0.50. High Resolution-Transmission Electron Microscopy image represents the spherical and smooth surface of nanoparticles. The results suggested that, quercetin loaded polymeric nanoparticles may be the viable strategy for controlled release for more than 48 hours, and improves the physical stability of quercetin.

Alginate-coated quaternized chitosan nanoparticles for oral delivery of insulin

Alginate-coated quaternized chitosan nanoparticles for oral delivery of insulin

Serratiopeptidase loaded chitosan nanoparticles by polyelectrolyte complexation: in vitro and in vivo evaluation.

The aim of the present study was to formulate serratiopeptidase (SER)-loaded chitosan (CS) nanoparticles for oral delivery. SER is a proteolytic enzyme which is very sensitive to change in temperature and pH. SER-loaded CS nanoparticles were fabricated by ionic gelation method using tripolyphosphate (TPP). Nanoparticles were characterized for its particle size, morphology, entrapment efficiency, loading efficiency, percent recovery, and in vitro dissolution study. SER-CS nanoparticles had a particle size in the range of 400-600 nm with polydispersity index below 0.5. SER association was up to 80 ± 4.2%. SER loading and CS/TPP mass ratio were the primary parameters having direct influence on SER-CS nanoparticles. SER-CS nanoparticles were freeze dried using trehalose (20%) as a cryoprotectant. In vitro dissolution showed initial burst followed by sustained release up to 24 h. In vivo anti-inflammatory activity was carried out in rat paw edema model. In vivo anti-inflammatory activity in rat paw edema showed prolonged anti-inflammatory effect up to 32 h relative to plain SER.

Nanoparticulate Delivery Can Improve &lt;I&gt;Peroral&lt;/I&gt; Bioavailability of Cyclosporine and Match Neoral C&lt;SUB&gt;max&lt;/SUB&gt; Sparing the Kidney from Damage

Cyclosporine (CsA) as an immunosuppressant has demonstrated immense potential in the field of organ transplantation and autoimmune disorders, despite the nephrotoxicity. The present investigation is an attempt to develop biodegradable nanoparticles entrapping CsA that can match Cmax of Neora, the most potent formulation available to date. The Cmax and AUC0-72 of CsA administered as nanoparticles demonstrated an increase with increase in the dose administered, however the relative bioavailability decreased. The Cmax and AUC0-72 increased from 682 to 1073 ng/ml and 34854 to 55322 ng . h/ml, respectively whereas, the relative bioavailability decreased from 120 to 64%. On the other hand, the increase in initial CsA loading (10-30% w/w of polymer) recorded a proportional increase in Cmax and AUC0-72, from 494 to 1101 ng/ml and 17774 to 51763 ng . h/ml, respectively. The relative bioavailability also increased from 31 to 89%. The CsA nanoparticles at 30% CsA loading w/w of polymer and at 30 mg/Kg single dose demonstrated comparable Cmax of Neoral at 15 mg/Kg, which upon chronic administration over a period of 30 days daily dosing showed low nephrotoxicity to that exhibited by Neoral. The reduced toxicity of nanoparticulate CsA indicated by lower blood urea nitrogen, plasma creatinine and glomerular damage, was due to delay in Tmax as result of slow release of the CsA from the nanoparticles. The investigation unlocks the potential of polymeric nanoparticles in oral delivery of CsA.

Application of Nanoparticles in Oral Delivery of Immediate Release Formulations

Application of Nanoparticles in Oral Delivery of Immediate Release Formulations