Polymer coated liposomes for use in the oral cavity – a study of the in vitro toxicity,effect on cell permeability and interaction with mucin

In this study we investigated the in vitro toxicity, impact on cell permeability and mucoadhesive potential of polymer-coated liposomes intended for use in the oral cavity. A TR146 cell line was used as a model. The overall aim was to end up with a selection of safe polymer coated liposomes with promising mucoadhesive properties for drug delivery to the oral cavity. The following polymers were tested: chitosan, low-methoxylated pectin (LM-pectin), high-methoxylated pectin (HM-pectin), amidated pectin (AM-pectin), Eudragit, poly(N-isopropylacrylamide-co-methacrylic acid) (p(NIPAAM-co-MAA)), hydrophobically modified hydroxyethyl cellulose (HM-HEC), and hydrophobically modified ethyl hydroxyethyl cellulose (HM-EHEC). With chitosan as an exception, all the systems exhibited no significant effect on cell viability and permeability at the considered concentrations. Additionally, all the formulations showed to a varying degree an interaction with mucin (BSM type I-S); the positively charged formulations exhibited the strongest interaction, while the negatively and neutrally charged formulations displayed a moderate or low interaction. The ability to interact with mucin makes all the liposomal formulations promising for oromucosal administration. Although the chitosan-coated liposomes affected the cell viability, this formulation also influenced the cell permeability, which makes it an interesting candidate for systemic drug delivery from the oral cavity.     

Chitosan nanoparticles for oral drug and gene delivery

Chitosan is a widely available, mucoadhesive polymer that is able to increase cellular permeability and improve the bioavailability of orally administered protein drugs. It can also be readily formed into nanoparticles able to entrap drugs or condense plasmid DNA. Studies on the formulation and oral delivery of such chitosan nanoparticles have demonstrated their efficacy in enhancing drug uptake and promoting gene expression. This review summarizes some of these findings and highlights the potential of chitosan as a component of oral delivery systems.     

Mucoadhesive bilayered tablets for buccal sustained release of flurbiprofen

The aim of this work was the design of sustained-release mucoadhesive bilayered tablets, using mixtures of mucoadhesive polymers and an inorganic matrix (hydrotalcite), for the topical administration of flurbiprofen in the oral cavity. The first layer, responsible for the tablet retention on the mucosa, was prepared by compression of a cellulose derivative and polyacrylic derivative blend. The second layer, responsible for buccal drug delivery, was obtained by compression of a mixture of the same (first layer) mucoadhesive polymers and hydrotalcite containing flurbiprofen. Nonmedicated tablets were evaluated in terms of swelling, mucosal adhesion, and organoleptic characteristics; in vitro and in vivo release studies of flurbiprofen-loaded tablets were performed as well. The best results were obtained from the tablets containing 20 mg of flurbiprofen, which allowed a good anti-inflammatory sustained release in the buccal cavity for 12 hours, ensuring efficacious salivary concentrations, and led to no irritation. This mucoadhesive formulation offers many advantages over buccal lozenges because it allows for reduction in daily administrations and daily drug dosage and is suitable for the treatment of irritation, pain, and discomfort associated with gingivitis, sore throats, laryngopharyngitis, cold, and periodontal surgery. Moreover, it adheres well to the gum and is simple to apply, which means that patient compliance is improved. Published: July 13, 2007     

Oral bioavailability and drug/carrier particulate systems

The oral route remains the preferred route of administration to ensure patient satisfaction and compliance. However, new chemical entities may exhibit low bioavailability after oral administration because of poor stability within the gastrointestinal tract, poor solubility in gastrointestinal fluids, low mucosal permeability, and/or extensive first-pass metabolism. Consequently, these new drug substances cannot be further developed using conventional oral formulations. This issue is addressed by an innovative approach based on the entrapment of drug molecules in drug/carrier assembling systems. The carrier materials are lipids, naturally occurring polymers or synthetic polymers, which are considered as nontoxic and biocompatible materials. Drug entrapment is intended to protect drug substances against degradation by gastrointestinal fluids. Fine drug/carrier particle size ensures increased drug dissolution rates. Carriers and particle supramolecular organization can be designed to enhance drug absorption through the intestinal epithelium and lymphatic transport. Promising preclinical results have been obtained with model drugs like paclitaxel, insulin, calcitonin, or cyclosporin. Attention has focused on mucoadhesive carriers like chitosan that favor an intimate and extended contact between drugs and intestinal cells, thus enhancing absorption. Addition of ligands such as lectins improves intestinal drug absorption through specific binding of the carrier to intestinal cell carbohydrates. In conclusion, drug/carrier particulate systems are an attractive and exciting drug delivery strategy for highly potent drug substances unsuitable for oral use. Further evidence will determine whether this approach has marked therapeutic benefits over conventional drug formulations and is compatible with large-scale industrial production and stringent registration requirements. Producing highly effective particulate systems requiring low-complexity manufacturing processes is therefore an ongoing challenge.     

The Effect of Inkjet Printing over Polymeric Films as Potential Buccal Biologics Delivery Systems

The buccal mucosa appears as a promissory route for biologic drug administration, and pharmaceutical films are flexible dosage forms that can be used in the buccal mucosa as drug delivery systems for either a local or systemic effect. Recently, thin films have been used as printing substrates to manufacture these dosage forms by inkjet printing. As such, it is necessary to investigate the effects of printing biologics on films as substrates in terms of their physical and mucoadhesive properties. Here, we explored solvent casting as a conventional method with two biocompatible polymers, hydroxypropyl methylcellulose, and chitosan, and we used electrospinning process as an electrospun film fabrication of polycaprolactone fibers due to its potential to elicit mucoadhesion. Lysozyme was used as biologic drug model and was formulated as a solution for printing by thermal inkjet printing. Films were characterized before and after printing by mechanical and mucoadhesive properties, surface, and ultrastructure morphology through scanning electron microscopy and solid state properties by thermal analysis. Although minor differences were detected in micrographs and thermograms in all polymeric films tested, neither mechanical nor mucoadhesive properties were affected by these differences. Thus, biologic drug printing on films was successful without affecting their mechanical or mucoadhesive properties. These results open way to explore biologics loading on buccal films by inkjet printing, and future efforts will include further in vitro and in vivo evaluations.     

Nanoparticles incorporated in bilaminated films: a smart drug delivery system for oral formulations

A novel smart drug delivery system (NP-Film) consisting of carboxylation chitosan-grafted nanoparticles (CCGNs) and bilaminated films, which were composed of the mucoadhesive chitosan-ethylenediaminetetraacetic acid hydrogel layer and the hydrophobic ethylcellulose layer, was developed for oral delivery of protein drugs. NP-Film was characterized by electron microscopy and fluorescence microscopy, and the results showed that the solid, spherical nanoparticles dispersed evenly in the porous structures of films. The properties of nanoparticles and films were investigated. The mucoadhesive force, CCGNs released from the NP-Film, and the toxicity of NP-Film were also evaluated. Results showed that the nanoparticles could reversibly open the tight junction of the intestine and inhibit trypsin activity. The release behavior of the nanoparticles from the NP-Film exhibited pH sensitivity. The drug delivery system possessed high mucoadhesive force and low intestinal toxicity. Therefore, the NP-Film would be a promising delivery carrier for protein drugs via oral administration.     

Design and Development of Gliclazide Mucoadhesive Microcapsules: In Vitro and In Vivo Evaluation

In this study an attempt was made to prepare mucoadhesive microcapsules of gliclazide using various mucoadhesive polymers designed for oral controlled release. Gliclazide microcapsules were prepared using sodium alginate and mucoadhesive polymer such as sodium carboxymethyl cellulose (sodium CMC), carbopol 934P or hydroxy propylmethyl cellulose (HPMC) by orifice-ionic gelation method. The microcapsules were evaluated for surface morphology and particle shape by scanning electron microscope. Microcapsules were also evaluated for their microencapsulation efficiency, in vitro wash-off mucoadhesion test, in vitro drug release and in vivo study. The microcapsules were discrete, spherical and free flowing. The microencapsulation efficiency was in the range of 65–80% and microcapsules exhibited good mucoadhesive property in the in vitro wash off test. The percentage of microcapsules adhering to tissue at pH 7.4 after 6 h varied from 12–32%, whereas the percentage of microcapsules adhering to tissue at pH 1.2 after 6 h varied from 35–68%. The drug release was also found to be slow and extended for more than 16 h. In vivo testing of the mucoadhesive microcapsules in diabetic albino rats demonstrated significant antidiabetic effect of gliclazide. The hypoglycemic effect obtained by mucoadhesive microcapsules was for more than 16 h whereas gliclazide produced an antidiabetic effect for only 10 h suggesting that mucoadhesive microcapsules are a valuable system for the long term delivery of gliclazide.     

Isolation and evaluation of a polysaccharide from Prunus amygdalus as a carrier for transbuccosal delivery of Losartan potassium

An oral buccoadhesive drug delivery system for Losartan potassium using a hydrophilic polysaccharide, isolated from Prunus amygdalaus (Badam gum), was developed and evaluated for its potential to overcome the drawbacks associated with the conventional drug therapy. The results of the study indicate that the isolated polysaccharide has good physicochemical and morphological characteristics and is suitable for use as a mucoadhesive sustain release polymer in pharmaceutical dosage forms, to alleviate the drawbacks of the conventional drug therapy of Losartan potassium.     

Thermosensitive and mucoadhesive delivery systems of mucosal vaccines

Mucosal vaccination is emerging as a potential administration route for eliciting antigen-specific mucosal and systemic immunogenicity. Most mucosal vaccines have been administered in a phosphate-buffered saline vehicle that may limit the exposure of antigens to the mucosal surfaces and result in poor immunogenicity. To improve the potency of the mucosal vaccines, we have developed mucosal vaccine delivery systems that might prevent leakage and increase retention of vaccines on mucosal surfaces. Thermosensitive polymers have been used to reduce the leakage problems of nasal or vaginal vaccines, while mucoadhesive polymers have been employed to increase the mucosal contact of the vaccines. Here, we describe the formulation and delivery methods of mucosal vaccines using thermosensitive and mucoadhesive polymers.     

Overview and Future Potential of Buccal Mucoadhesive Films as Drug Delivery Systems for Biologics

The main route of administration for drug products is the oral route, yet biologics are initially developed as injectables due to their limited stability through the gastrointestinal tract and solubility issues. In order to avoid injections, a myriad of investigations on alternative administration routes that can bypass enzymatic degradation and the first-pass effect are found in the literature. As an alternative site for biologics absorption, the buccal route presents with a number of advantages. The buccal mucosa is a barrier, providing protection to underlying tissue, but is more permeable than other alternative routes such as the skin. Buccal films are polymeric matrices designed to be mucoadhesive properties and usually formulated with permeability enhancers to improve bioavailability. Conventionally, buccal films for biologics are manufactured by solvent casting, yet recent developments have shown the potential of hot melt extrusion, and most recently ink jet printing as promising strategies. This review aims at depicting the field of biologics-loaded mucoadhesive films as buccal drug delivery systems. In light of the literature available, the buccal epithelium is a promising route for biologics administration, which is reflected in clinical trials currently in progress, looking forward to register and commercialize the first biologic product formulated as a buccal film.     

生物相容透皮给药微针治疗浅表肿瘤

复杂的肿瘤微环境导致抗肿瘤药物在肿瘤组织内递送效率低下，严重阻碍了药物对浅表肿瘤的治疗效果。生物相容透皮给药微针凭借较高的机械强度，刺穿皮肤角质层，将微针内的药物递送至浅表肿瘤组织内，提高生物利用度，改善静脉注射、口服给药的肝肾毒性等问题。本文介绍了生物相容透皮给药微针的设计及其在癌症化疗、光动力治疗、光热治疗、免疫治疗、基因治疗等领域的研究进展，对浅表肿瘤的微创、局部递药和精准、高效治疗具有重要指导意义。     

Formulation and In Vitro Evaluation of Salbutamol Sulphate In Situ Gelling Nasal Inserts

The aim of this study was to formulate salbutamol sulfate (SS), a model drug, as mucoadhesive in situ gelling inserts having a high potential as nasal drug delivery system bypassing the first-pass metabolism. In situ gelling inserts, each containing 1.4% SS and 2% gel-forming polymer, hydroxypropyl methylcellulose (HPMC), carboxymethylcellulose sodium (CMC Na), sodium alginate (AL), and chitosan (CH) were prepared. The inserts were investigated for their different physicochemical properties. The weight of inserts was 16–27 mg, drug content was 3.9–4.2 mg, thickness ranged between 15 and 28 μm and surface pH was 5–7. Cumulative drug released from the inserts exhibited extended release for more than 10 h following the decreasing order: CH > AL > CMC Na > HPMC. The drug release from CMC Na and AL inserts followed zero-order kinetics while HPMC and CH inserts exhibited non-Fickian diffusion mechanism. The inserts exhibited different water uptake (7–23%) with the smallest values for CH. Differential scanning calorimetry study pointed out possible interaction of SS and oppositely charged anionic polymers (CMC Na and AL). The mucoadhesive in situ gelling inserts exhibited satisfactory mucoadhesive and extended drug release characteristics. The inserts could be used for nasal delivery of SS over about 12 h; bypassing the hepatic first-pass metabolism without potential irritation.KEY WORDS: in situ gelling inserts, mucoadhesion, nasal delivery, salbutamol sulfate     

Recent Advancement of Chitosan-Based Nanoparticles for Oral Controlled Delivery of Insulin and Other Therapeutic Agents

Nanoparticles composed of naturally occurring biodegradable polymers have emerged as potential carriers of various therapeutic agents for controlled drug delivery through the oral route. Chitosan, a cationic polysaccharide, is one of such biodegradable polymers, which has been extensively exploited for the preparation of nanoparticles for oral controlled delivery of several therapeutic agents. In recent years, the area of focus has shifted from chitosan to chitosan derivatized polymers for the preparation of oral nanoparticles due to its vastly improved properties, such as better drug retention capability, improved permeation, enhanced mucoadhesion and sustained release of therapeutic agents. Chitosan derivatized polymers are primarily the quaternized chitosan derivatives, chitosan cyclodextrin complexes, thiolated chitosan, pegylated chitosan and chitosan combined with other peptides. The current review focuses on the recent advancements in the field of oral controlled release via chitosan nanoparticles and discusses about its in vitro and in vivo implications.     

A comprehensive development strategy in buccal drug delivery

This work combines several methods in an integrated strategy to develop a matrix for buccal administration. For this purpose, tablets containing selected mucoadhesive polymers loaded with a model drug (omeprazole), free or in a complexed form with cyclodextrins, and in the absence and presence of alkali agents were subjected to a battery of tests. Mucoadhesion studies, including simple factorial analysis, in vitro release studies with both model-dependent and model-independent analysis, and permeation studies were performed. Mucoadhesive profiles indicated that the presence of the drug decreases the mucoadhesion profile, probably due its hydrophobic character. In tablets loaded with the drug complexed with β-cyclodextrin or methyl-β-cyclodextrin, better results were obtained with the methylated derivative. This effect was attributed to the fact that in the case of β-cyclodextrin, more hydroxyl groups are available to interact with the mucoadhesive polymers, thus decreasing the mucoadhesion performance. The same result was observed in presence of the alkali agent (l-arginine), in this case due to the excessive hydrophilic character of l-arginine. Drug release from tablets was also evaluated, and results suggested that the dissolution profile with best characteristics was observed in the matrix loaded with omeprazole complexed with methyl-β-cyclodextrin in the presence of l-arginine. Several mathematical models were applied to the dissolution curves, indicating that the release of the drug, in free or in complexed state, from the mucoadhesive matrices followed a super case II transport, as established on the basis of the Korsmeyer–Peppas function. The feasibility of drug buccal administration was assessed by permeation experiments on porcine buccal mucosa. The amount of drug permeated from mucoadhesive tablets presented a maximum value for the system containing drug complexed with the methylated cyclodextrin derivative in presence of l-arginine. According to these results, the system containing the selected polymer mixture and the drug complexed with methyl-β-cyclodextrin in presence of l-arginine showed a great potential as a buccal drug delivery formulation, in which a good compromise among mucoadhesion, dissolution, and permeation properties was achieved.     

Intranasal Cabergoline: Pharmacokinetic and Pharmacodynamic Studies

Aims of this investigation were to prepare and characterize cabergoline intranasal microemulsion formulations, determine brain drug delivery through biodistribution using technetium-99m (^99mTc) as a tracer, and assess its performance pharmacodynamically in weight control. Cabergoline microemulsions of different compositions were prepared by water titration method and characterized for globule size and zeta potential. Microemulsion with maximum drug solubilization and stability was considered optimal and taken for further studies with or without addition of mucoadhesive agent. Pharmacokinetics of optimized ^99mTc-labeled cabergoline formulations and ^99mTc-labeled drug solution were studied by estimating radioactivity in brain and blood of albino rats post intranasal, intravenous, and oral administrations. To confirm localization of drug in brain following intranasal, intravenous, and oral administrations, gamma scintigraphy imaging was also performed. To assess weight control performance of formulations, body weight, white adipose tissue mass, serum lipids, leptin, and prolactin were determined before and after 40 days of intranasal administrations of these formulations to Wistar rats. Microemulsions were found to be stable both physically and chemically when stored at various stress conditions. Brain/blood uptake ratios, drug targeting efficiency, and direct drug transport were found to be highest for drug mucoadhesive microemulsion followed by drug microemulsion and drug solution post-intranasal administration compared to intravenous drug microemulsion. Significant (p < 0.05) reduction in assessed pharmacodynamic parameters was observed after intranasal administration of mucoadhesive microemulsion against control group. The results of the studies conclusively demonstrate that intranasal microemulsion formulations developed in this investigation are stable and can deliver cabergoline selectively and in higher amounts to the brain compared to both drug administrations as a solution intranasally or microemulsion intravenously. The results also demonstrate reduction in weight, adipose tissue mass, serum lipids, and serum prolactin after intranasal administration of drug microemulsion. Hence, long-term studies in at least two more animal models followed by extensive clinical evaluation can safely result into a product for clinical use.     

Water-based nanoparticulate polymeric system for protein delivery: permeability control and vaccine application

The idea of using polymeric nanoparticles as drug carriers is receiving an increasing amount of attention both in academia and industry, Nanoparticles have a number of potential applications in protein, drug and vaccine delivery, as well as gene therapy applications. In this article, we focus on this unique drug delivery technology as a method to control the release rate of substances, not only for protein delivery but also for delivering an experimental vaccine immunogen. Nanoparticles were assembled on the basis of ionic interaction between water-soluble polymers so that the resulting particles were stable in physiologic media. Among the typical polymers used to assemble nanoparticles, different polysaccharides, natural amines, and poly-amines were investigated. The entrapped substances tested included a protein and antigens. Polydextran aldehyde was incorporated into the particle core, to enable physiologic cross-linking as a method to control permeability. This resulted in long-term retention of substances that would otherwise rapidly leak out of the nanoparticles. Results of cross-linking experiments clearly demonstrated that the release rate could be substantially reduced, depending on the degree of cross-linking. For vaccine antigen delivery tests, we measured an antibody production after subcutaneous and oral administration. The data indicated that only the cross-linked antigen was immunogenic when the oral route of administration was used. The data presented in this article address primarily the utility of nanoparticulates for oral delivery of vaccine antigen.     

Design and <Emphasis Type="Italic">In Vitro</Emphasis> Performance Evaluation of Purified Microparticles of Pravastatin Sodium for Intestinal Delivery

The purpose of research was to develop a mucoadhesive multiparticulate sustained drug delivery system of pravastatin sodium, a highly water-soluble and poorly bioavailable drug, unstable at gastric pH. Mucoadhesive microparticles were formulated using eudragit S100 and ethyl cellulose as mucoadhesive polymers. End-step modification of w/o/o double emulsion solvent diffusion method was attempted to improve the purity of the product, that can affect the dose calculations of sustained release formulations and hence bioavailability. Microparticles formed were discrete, free flowing, and exhibited good mucoadhesive properties. DSC and DRS showed stable character of drug in microparticles and absence of drug polymer interaction. The drug to polymer ratio and surfactant concentration had significant effect on mean particle size, drug release, and entrapment efficiency. Microparticles made with drug: eudragit S100 ratio of 1:3 (F6) exhibited maximum entrapment efficiency of 72.7% and ex vivo mucoadhesion time of 4.15 h. In vitro permeation studies on goat intestinal mucosa demonstrated a flux rate (1,243 μg/cm²/h) that was 169 times higher than the flux of pure drug. The gastric instability problem was overcome by formulating the optimized microparticles as enteric-coated capsules that provided a sustained delivery of the highly water-soluble drug for 12 h beyond the gastric region. The release mechanism was identified as fickian diffusion (n = 0.4137) for the optimized formulation F6. Conclusively, a drug delivery system was successfully developed that showed delayed and sustained release up to 12 h and could be potentially useful to overcome poor bioavailability problems associated with pravastatin sodium.     

Mucoadhesive Properties of Eudragit®RS100, Eudragit®S100, and Poly(ε-caprolactone) Nanocapsules: Influence of the Vehicle and the Mucosal Surface

The use of polymers as mucoadhesive materials has been explored in several drug delivery systems. It is well known that the resulting mucoadhesiveness not only depends on the polymers by themselves, but also on the way they are delivered and on the application target. However, little attention has been given to the combined effect of such characteristics. Therefore, the objective of this study is to analyze the mucoadhesion resulting from combined effects of nanocapsules produced with polymers of different ionic properties, Eudragit®RS100, Eudragit®S100, or poly(ε-caprolactone), when they are incorporated into different vehicles (suspension, hydrogel, and powder) and applied on different mucosal surfaces (mucin, porcine vaginal, and buccal mucosa). Mucoadhesion was measured by a tensile stress tester. Our findings show that polymeric self-assembling as nanocapsules improved the mucoadhesion of the polymers. Eudragit®RS100 nanocapsules have the best performance, independently of the vehicle and surface used. Regarding the vehicle, hydrogels showed higher adhesion when compared to suspensions and powders. When considering different types of surfaces, mucin presented a similar pattern like the animal mucosa, but it overestimated the mucoadhesiveness of all formulations. In conclusion, this study demonstrated that the best strategy to achieve high mucoadhesive formulations is by incorporating Eudragit®RS100 nanocapsules in hydrogels. Moreover, mucin is a suitable substrate to compare and screen different formulations but not as a conclusive estimation of the mucoadhesion values that can be achieved. These results are summarized in a decision tree that can help to understand different strategies of combination of these factors and the expected outcomes.     

Anti-<Emphasis Type="Italic">Helicobacter pylori</Emphasis> effect of mucoadhesive nanoparticles bearing amoxicillin in experimental gerbils model

The purpose of the present study was to design mucoadhesive gliadin nanoparticles (GNP) containing amoxicillin and to evaluate their effectiveness in eradicating Helicobacter pylori. GNP-bearing amoxicillin (AGNP) was prepared by desolvation method. The effect of process variables such as gliadin concentration and initial drug loading on particle size, shape, percent payload, percent entrapment efficiency, in vitro release profile, and mucoadhesive property of GNP was assessed. Rhodamine isothiocyanate-entrapped GNP formulations were prepared to evaluate their in vivo gastric mucoadhesive property in albino rats. With increasing gliadin concentration, the mucoadhesive property of GNP increased. Typically, the maximum amount of nanoparticles remaining was 82±4%, which represented a stronger mucoadhesive propensity and specificity of GNP toward the stomach. In vitro antimicrobial activity of AGNP was evaluated by growth inhibition studies on an isolated H pylori strain. The time required for complete eradication was higher in AGNP than in amoxicillin because of the controlled drug delivery of amoxicillin from AGNP. In vivo clearance of H pylori following oral administration of AGNP to infected Mongolian gerbils was examined. Amoxicillin and AGNP both showed anti-H pylori effects in this experimental model of infection, but the required dose for complete eradication was less in AGNP than in amoxicillin. In conclusion, AGNP eradicated H pylori from the gastrointestinal tract more effectively than amoxicillin because of the prolonged gastrointestinal residence time attributed to mucoadhesion. A dosage form containing mucoadhesive nanoparticles bearing a potential antibiotic should be useful for the complete eradication of H pylori.     

Metformin-Loaded Hyaluronic Acid Nanostructure for Oral Delivery

The objective of this study was to develop a nanodelivery system containing a mucoadhesive polymer hyaluronic acid (HA) for oral delivery. Metformin was used as a model drug. Blank and drug-loaded HA nanostructures were prepared by precipitation method and characterized for particle size (PS), zeta potential (ZP), physical stability (over 65 days), surface morphology, moisture content, and physical state of the drug in the nanostructures. The cytotoxicity and hemolysis potential of the delivery system was assessed in Caco-2 cells and whole human blood, respectively. The in vitro release of metformin and its uptake in Caco-2 cells was evaluated using high-performance liquid chromatography. Ex vivo permeability of metformin was measured through goat intestinal membrane. The nanoparticles were physically stable and neutrally charged with an average PS of 114.53?±?12.01 nm. This nanodelivery system existed as nanofibers containing metformin in a crystalline state. This delivery system released the drug rapidly with >?50% of metformin released within 1 h. Cellular uptake studies on Caco-2 cells indicated higher uptake of metformin from nanoparticle as compared to metformin in solution, up to first 45 min. Ex vivo permeability studies on the other hand showed a higher metformin permeability from solution relative to that from nanoparticles through the goat intestinal membrane. Metformin nanoparticles were non-toxic at therapeutic concentrations in Caco-2 cells and showed no hemolytic effect to RBCs. This study indicates the preparation, characterization, as well as the potential use of HA nanostructures for oral delivery.