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Sample records for mucoadhesive drug delivery

  1. Mucoadhesive drug delivery systems

    PubMed Central

    Shaikh, Rahamatullah; Raj Singh, Thakur Raghu; Garland, Martin James; Woolfson, A David; Donnelly, Ryan F.

    2011-01-01

    Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal). PMID:21430958

  2. Mucoadhesive vaginal drug delivery systems.

    PubMed

    Acartürk, Füsun

    2009-11-01

    Vaginal delivery is an important route of drug administration for both local and systemic diseases. The vaginal route has some advantages due to its large surface area, rich blood supply, avoidance of the first-pass effect, relatively high permeability to many drugs and self-insertion. The traditional commercial preparations, such as creams, foams, gels, irrigations and tablets, are known to reside in the vaginal cavity for a relatively short period of time owing to the self-cleaning action of the vaginal tract, and often require multiple daily doses to ensure the desired therapeutic effect. The vaginal route appears to be highly appropriate for bioadhesive drug delivery systems in order to retain drugs for treating largely local conditions, or for use in contraception. In particular, protection against sexually-transmitted diseases is critical. To prolong the residence time in the vaginal cavity, bioadhesive therapeutic systems have been developed in the form of semi-solid and solid dosage forms. The most commonly used mucoadhesive polymers that are capable of forming hydrogels are synthetic polyacrylates, polycarbophil, chitosan, cellulose derivatives (hydroxyethycellulose, hydroxy-propylcellulose and hydroxypropylmethylcellulose), hyaluronic acid derivatives, pectin, tragacanth, carrageenan and sodium alginate. The present article is a comprehensive review of the patents related to mucoadhesive vaginal drug delivery systems.

  3. Thiolated polymers as mucoadhesive drug delivery systems.

    PubMed

    Duggan, Sarah; Cummins, Wayne; O' Donovan, Orla; Hughes, Helen; Owens, Eleanor

    2017-03-30

    Mucoadhesion is the process of binding a material to the mucosal layer of the body. Utilising both natural and synthetic polymers, mucoadhesive drug delivery is a method of controlled drug release which allows for intimate contact between the polymer and a target tissue. It has the potential to increase bioavailability, decrease potential side effects and offer protection to more sensitive drugs such as proteins and peptide based drugs. The thiolation of polymers has, in the last number of years, come to the fore of mucoadhesive drug delivery, markedly improving mucoadhesion due to the introduction of free thiol groups onto the polymer backbone while also offering a more cohesive polymeric matrix for the slower and more controlled release of drug. This review explores the concept of mucoadhesion and the recent advances in both the polymers and the methods of thiolation used in the synthesis of mucoadhesive drug delivery devices.

  4. Mucoadhesive drug delivery system: An overview

    PubMed Central

    Boddupalli, Bindu M.; Mohammed, Zulkar N. K.; Nath, Ravinder A.; Banji, David

    2010-01-01

    Mucoadhesive drug delivery systems interact with the mucus layer covering the mucosal epithelial surface, and mucin molecules and increase the residence time of the dosage form at the site of absorption. The drugs which have local action or those which have maximum absorption in gastrointestinal tract (GIT) require increased duration of stay in GIT. Thus, mucoadhesive dosage forms are advantageous in increasing the drug plasma concentrations and also therapeutic activity. In this regard, this review covers the areas of mechanisms and theories of mucoadhesion, factors influencing the mucoadhesive devices and also various mucoadhesive dosage forms. PMID:22247877

  5. Mucoadhesive polymeric platforms for controlled drug delivery.

    PubMed

    Andrews, Gavin P; Laverty, Thomas P; Jones, David S

    2009-03-01

    The process of mucoadhesion involving a polymeric drug delivery platform is a complex one that includes wetting, adsorption and interpenetration of polymer chains amongst various other processes. The success and degree of mucoadhesion bonding is influenced by various polymer-based properties such as the degree of cross-linking, chain length and the presence of various functional groupings. The attractiveness of mucosal-targeted controlled drug delivery of active pharmaceutical ingredients (APIs), has led formulation scientists to engineer numerous polymeric systems for such tasks. Formulation scientists have at their disposal a range of in vitro and in vivo mucoadhesion testing setups in order to select candidate adhesive drug delivery platforms. As such, mucoadhesive systems have found wide use throughout many mucosal covered organelles for API delivery for local or systemic effect. Evolution of such mucoadhesive formulations has transgressed from first-generation charged hydrophilic polymer networks to more specific second-generation systems based on lectin, thiol and various other adhesive functional groups.

  6. Mucoadhesive polymeric platform for drug delivery; a comprehensive review.

    PubMed

    Agarwal, Shweta; Aggarwal, Shikha

    2015-01-01

    Mucoadhesion can be defined as adhesion in biological setting. Process of mucoadhesion takes place in 3 stages- the first stage being that of wetting or swelling of mucoadhesive polymer. Second stage involves interpenetration of the chains of mucoadhesive polymer and the third stage involves formation of chemical bonds between entangled chains. Several polymer related factors like molecular weight, chain length, degree of cross-linking, hydration, functional groups, charge, polymer concentration and several environmental and physiological factors like contact time, mucin turnover rate and mucus viscosity affect the degree of mucoadhesion. Formulation scientists have structured and engineered several mucoadhesive polymers for their usefulness in enhancement of bioavailability, controlled and targeted drug delivery. Mucoadhesive polymers can be classified as non-specific first generation polymers and novel second generation polymers based on the mechanism of mucoadhesion. Mucoadhesive drug delivery systems have been applied to buccal cavity, oesophagus, gastrointestinal tract, eye, nasal cavity, vagina and rectal cavity. Several in vitro/ex vivo and in vivo evaluation techniques have evolved for the evaluation of mucoadhesive strength of these polymers. This review provides historical perspective on mucoadhesive polymers and an understanding of the phenomenon of mucoadhesion, factors affecting mucoadhesion, types of mucoadhesive polymers, their practical applications and the various evaluation techniques for determination of mucoadhesive strength.

  7. A clinical perspective on mucoadhesive buccal drug delivery systems

    PubMed Central

    Gilhotra, Ritu M; Ikram, Mohd; Srivastava, Sunny; Gilhotra, Neeraj

    2014-01-01

    Mucoadhesion can be defined as a state in which two components, of which one is of biological origin, are held together for extended periods of time by the help of interfacial forces. Among the various transmucosal routes, buccal mucosa has excellent accessibility and relatively immobile mucosa, hence suitable for administration of retentive dosage form. The objective of this paper is to review the works done so far in the field of mucoadhesive buccal drug delivery systems (MBDDS), with a clinical perspective. Starting with a brief introduction of the mucoadhesive drug delivery systems, oral mucosa, and the theories of mucoadhesion, this article then proceeds to cover the works done so far in the field of MBDDS, categorizing them on the basis of ailments they are meant to cure. Additionally, we focus on the various patents, recent advancements, and challenges as well as the future prospects for mucoadhesive buccal drug delivery systems. PMID:24683406

  8. Acrylated chitosan for mucoadhesive drug delivery systems.

    PubMed

    Shitrit, Yulia; Bianco-Peled, Havazelet

    2017-01-30

    A new mucoadhesive polymer was synthesized by conjugating chitosan to poly(ethylene glycol)diacrylate (PEGDA) via the Michael type reaction. The product was characterized using NMR. Higher PEGDA grafting efficacy was observed with low molecular weight PEGDA (0.7kDa), compared to long 10kDa PEGDA. The acrylation percentage was calculated based on the reaction of ninhydrin with chitosan, and supported the qualitative NMR findings. The adhesive properties were studied by tensile test and rotating system involving detachment of polymer tablets from a fresh intestine sample. Chitosan modified with high molecular weight PEGDA presented improvement in mucoadhesive properties compared to both non-modified and thiolated chitosan. On the molecular level, rheology measurements of polymer/mucin mixtures provided additional evidence of strong interaction between modified chitosan and mucin glycoproteins. This new polymer shows promise as a useful polymeric carrier matrix for delivery systems, which could provide prolonged residence time of the vehicle on the mucosa surface. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Thiopyrazole preactivated chitosan: combining mucoadhesion and drug delivery.

    PubMed

    Müller, Christiane; Ma, Benjamin N; Gust, Ronald; Bernkop-Schnürch, Andreas

    2013-05-01

    The objective of this study was to develop a preactivated chitosan derivative by the introduction of thioglycolic acid followed by 3-methyl-1-phenylpyrazole-5-thiol (MPPT) coupling via disulfide bond formation. The newly synthesized conjugate was characterized in terms of water-absorbing capacity, cohesive properties, mucoadhesion and drug release kinetics. Further in vitro characterization was conducted regarding permeation enhancement of the model compound fluorescein isothiocyanate dextran (FD4) and cytotoxic effects on Caco-2 cells. Based on the attachment of the hydrophobic residue, chitosan-S-S-MPPT test discs showed increased stability of the polymer matrix as well as improved water uptake and liberation of fluorescein isothiocyanate dextran (FD4) compared to chitosan only. The mucoadhesive qualities on porcine intestinal mucosa could be improved 38-fold based on the enhanced bonding between chitosan-S-S-MPPT and mucus through the thiol/disulfide exchange reaction of polymer and mucosal cysteine-rich domains supported by MPPT as the leaving group. This novel biomaterial presents a disulfide conjugation-based delivery system that releases the antibacterial thiopyrazole when the polymer comes into contact with the intestinal mucosa. These properties, together with the safe toxicological profile, make chitosan-S-S-MPPT a valuable carrier for mucoadhesive drug delivery systems and a promising matrix for the development of antimicrobial excipients.

  10. Novel mucoadhesion tests for polymers and polymer-coated particles to design optimal mucoadhesive drug delivery systems.

    PubMed

    Takeuchi, Hirofumi; Thongborisute, Jringjai; Matsui, Yuji; Sugihara, Hikaru; Yamamoto, Hiromitsu; Kawashima, Yoshiaki

    2005-11-03

    To design an effective particulate drug delivery system having mucoadhesive function, several mucoadhesion tests for polymers and the resultant particulate systems were developed. Mucin particle method is a simple mucoadhesion test for polymers, in which the commercial mucin particles are used. By measuring the change in particle size or zeta potential of the mucin particle in a certain concentration of polymer solution, we could estimate the extent of their mucoadhesive property. BIACORE method is also a novel mucoadhesion test for polymers. On passing through the mucin suspension on the polymer-immobilized chip of BIACORE instrument, the interaction was quantitatively evaluated with the change in its response diagram. By using these mucoadhesion tests, we detected a strong mucoadhesive property of several types of chitosan and Carbopol. Evaluation of mucoadhesive property of polymer-coated particulate systems was demonstrated with the particle counting method developed by us. To detect the mucoadhesive phenomena in the intestinal tract, we observed the rat intestine with the confocal laser scanning microscope (CLSM) after oral administration of the particulate systems. The resultant photographs clearly showed a longer retention of submicron-sized chitosan-coated liposomes (ssCS-Lip) in the intestinal tract than other liposomal particles tested such as non-coated liposomes and chitosan-coated multilamellar one. These observations explained well the superiority of the ssCS-Lip as drug carrier in oral administration of calcitonin in rats than other liposomal particles.

  11. Preactivated thiolated glycogen as mucoadhesive polymer for drug delivery.

    PubMed

    Perrone, Mara; Lopalco, Antonio; Lopedota, Angela; Cutrignelli, Annalisa; Laquintana, Valentino; Douglas, Justin; Franco, Massimo; Liberati, Elisa; Russo, Vincenzo; Tongiani, Serena; Denora, Nunzio; Bernkop-Schnürch, Andreas

    2017-10-01

    The purpose of this study was to synthesize and characterize a novel thiolated glycogen, so-named S-preactivated thiolated glycogen, as a mucosal drug delivery systems and the assessment of its mucoadhesive properties. In this regard, glycogen-cysteine and glycogen-cysteine-2-mercaptonicotinic acid conjugates were synthesized. Glycogen was activated by an oxidative ring opening with sodium periodate resulting in reactive aldehyde groups to which cysteine was bound via reductive amination. The obtained thiolated polymer displayed 2203.09±200μmol thiol groups per gram polymer. In a second step, the thiol moieties of thiolated glycogen were protected by disulfide bond formation with the thiolated aromatic residue 2-mercaptonicotinic acid (2MNA). In vitro screening of mucoadhesive properties was performed on porcine intestinal mucosa using different methods. In particular, in terms of rheology investigations of mucus/polymer mixtures, the S-preactivated thiolated glycogen showed a 4.7-fold increase in dynamic viscosity over a time period of 5h, in comparison to mucus/Simulated Intestinal Fluid control. The S-preactivated polymer remained attached on freshly excised porcine mucosa for 45h. Analogous results were obtained with tensile studies demonstrating a 2.7-fold increase in maximum detachment force and 3.1- fold increase in total work of adhesion for the S-preactivated polymer compared to unmodified glycogen. Moreover, water-uptake studies showed an over 4h continuing weight gain for the S-preactivated polymer, whereas disintegration took place for the unmodified polymer within the first hour. Furthermore, even in the highest tested concentration of 2mg/ml the new conjugates did not show any cytotoxicity on Caco-2 cell monolayer using an MTT assay. According to these results, S-preactivated glycogen represents a promising type of mucoadhesive polymers useful for the development of various mucosal drug delivery systems. Copyright © 2017 Elsevier B.V. All rights

  12. Polymer-cysteamine conjugates: new mucoadhesive excipients for drug delivery?

    PubMed

    Kast, Constantia E; Bernkop-Schnürch, Andreas

    2002-03-02

    In the present study, the features of two new thiolated polymers--the so-called thiomers--were investigated. Mediated by a carbodiimide cysteamine was covalently attached to sodium carboxymethylcellulose (Na-CMC) and neutralised polycarbophil (Na-PCP). Depending on the weight-ratio polymer to cysteamine during the coupling reaction, the resulting CMC-cysteamine conjugate and PCP-cysteamine conjugate showed in maximum 43 +/- 15 and 138 +/- 22 micromole thiol groups per g polymer (mean +/- S.D.; n=3), respectively, which were used for further characterisation. Tensile studies carried out with the CMC-cysteamine conjugate on freshly excised porcine intestinal mucosa displayed no significantly (P<0.01) improved mucoadhesion, whereas, the mucoadhesive properties of the PCP-cysteamine conjugate were increased 2.5-fold compared with the unmodified polymer. The swelling behaviour of the CMC-cysteamine conjugate was uninfluenced by the covalent attachment of the sulfhydryl compound. In contrast the swelling behaviour of the PCP-cysteamine conjugate was improved significantly (P<0.01) versus unmodified PCP. Furthermore, in aqueous solutions the disintegration time of tablets based on the CMC- and PCP-cysteamine conjugates was prolonged 1.5 and 3.2-fold, respectively, in comparison to tablets containing the corresponding unmodified polymers. According to these results, especially the PCP-cysteamine conjugate represents a promising new pharmaceutical excipient for various drug delivery systems.

  13. Preactivated thiomers as mucoadhesive polymers for drug delivery

    PubMed Central

    Iqbal, Javed; Shahnaz, Gul; Dünnhaupt, Sarah; Müller, Christiane; Hintzen, Fabian; Bernkop-Schnürch, Andreas

    2012-01-01

    found non-toxic over Caco-2 cells. Thus, on the basis of achieved results the pre-activated thiomers seem to represent a promising generation of mucoadhesive polymers which are safe to use for prolonged residence time of drug delivery systems to target various mucosa. PMID:22118819

  14. Chitosan in Mucoadhesive Drug Delivery: Focus on Local Vaginal Therapy

    PubMed Central

    Andersen, Toril; Bleher, Stefan; Flaten, Gøril Eide; Tho, Ingunn; Mattsson, Sofia; Škalko-Basnet, Nataša

    2015-01-01

    Mucoadhesive drug therapy destined for localized drug treatment is gaining increasing importance in today’s drug development. Chitosan, due to its known biodegradability, bioadhesiveness and excellent safety profile offers means to improve mucosal drug therapy. We have used chitosan as mucoadhesive polymer to develop liposomes able to ensure prolonged residence time at vaginal site. Two types of mucoadhesive liposomes, namely the chitosan-coated liposomes and chitosan-containing liposomes, where chitosan is both embedded and surface-available, were made of soy phosphatidylcholine with entrapped fluorescence markers of two molecular weights, FITC-dextran 4000 and 20,000, respectively. Both liposomal types were characterized for their size distribution, zeta potential, entrapment efficiency and the in vitro release profile, and compared to plain liposomes. The proof of chitosan being both surface-available as well as embedded into the liposomes in the chitosan-containing liposomes was found. The capability of the surface-available chitosan to interact with the model porcine mucin was confirmed for both chitosan-containing and chitosan-coated liposomes implying potential mucoadhesive behavior. Chitosan-containing liposomes were shown to be superior in respect to the simplicity of preparation, FITC-dextran load, mucoadhesiveness and in vitro release and are expected to ensure prolonged residence time on the vaginal mucosa providing localized sustained release of entrapped model substances. PMID:25574737

  15. Engineering Design and Molecular Dynamics of Mucoadhesive Drug Delivery Systems as Targeting Agents

    PubMed Central

    Serra, Laura; Doménech, Josep; Peppas, Nicholas

    2009-01-01

    The goal of this critical review is to provide a critical analysis of the chain dynamics responsible for the action of micro- and nanoparticles of mucoadhesive biomaterials. The objective of using bioadhesive controlled drug delivery devices is to prolong their residence at a specific site of delivery, thus enhancing the drug absorption process. These mucoadhesive devices can protect the drug during the absorption process in addition to protecting it on its route to the delivery site. The major emphasis of recent research on mucoadhesive biomaterials has been on the use of adhesion promoters, which would enhance the adhesion between synthetic polymers and mucus. The use of adhesion promoters such as linear or tethered polymer chains is a natural result of the diffusional characteristics of adhesion. Mucoadhesion depends largely on the structure of the synthetic polymer gels used in controlled release applications. PMID:18976706

  16. Mucoadhesive in situ nasal gelling drug delivery systems for modulated drug delivery.

    PubMed

    Singh, Reena M P; Kumar, Anil; Pathak, Kamla

    2013-01-01

    The nasal route is an attractive target for administration of the drug of choice, particularly in overcoming disadvantages such as high first-pass metabolism and drug degradation in the gastrointestinal environment that are associated with the oral and other modes of administration. The major limitation associated is of rapid mucociliary clearance in the nasal delivery that results in low absorption and hence poor bioavailability. In order to overcome this, mucoadhesive in situ nasal gelling drug delivery systems have been explored to develop sustained/controlled delivery via nasal route. The present review critically evaluates the importance of in situ gel for the nasal delivery of drugs, and the polymers used in the formulation of in situ gel along with their mechanism of gelation. It also encompasses the research reports made in this arena of delivery system. The challenges of drug delivery through nose has led to development of in situ nasal gelling systems using a myriad of polymers to deliver the drugs, proteins, amino acids, hormones, vaccines and plasmid DNA for the local, systemic and central nervous system effects. Though a range of preclinical reports are available, clinical intricacies need to be critically worked out.

  17. Ionic Gelation Controlled Drug Delivery Systems for Gastric-Mucoadhesive Microcapsules of Captopril

    PubMed Central

    Altaf, M. A.; Sreedharan; Charyulu, N.

    2008-01-01

    A new oral drug delivery system was developed utilizing both the concepts of controlled release and mucoadhesiveness, in order to obtain a unique drug delivery system which could remain in stomach and control the drug release for longer period of time. Captopril microcapsules were prepared with a coat consisting of alginate and a mucoadhesive polymer such as hydroxy propyl methyl cellulose, carbopol 934p, chitosan and cellulose acetate phthalate using emulsification ionic gelation process. The resulting microcapsules were discrete, large, spherical and free flowing. Microencapsulation efficiency was 41.7-89.7% and high percentage efficiency was observed with (9:1) alginate-chitosan microcapsules. All alginate-carbopol 934p microcapsules exhibited good mucoadhesive property in the in vitro wash off test. Drug release pattern for all formulation in 0.1 N HCl (pH 1.2) was diffusion controlled, gradually over 8 h and followed zero order kinetics. PMID:21394268

  18. Pluronic F127/chitosan blend microspheres for mucoadhesive drug delivery

    NASA Astrophysics Data System (ADS)

    Gu, W. Z.; Hu, X. F.

    2017-01-01

    Pluronic F127/chitosan blend microspheres were prepared via emulsification and cross-linking process using glutaraldehyde as a cross-linker. Compared with chitosan microspheres fabricated under the same experimental conditions, blend microspheres exhibited better physical stability and higher swelling capacity. Puerarin, a traditional Chinese medicine, was incorporated into microparticlesas the model drug. The in vitro release of puerarin from blend microspheres was reduced because of the improved compatibility of the drug with the matrices. According to the results from in vitro adhesion experiments, mucoadhesive behavior of blend microspheres on a mucosa-like surface was similar to that of chitosan microspheres, despite their good ability of anti-protein absorption in solution.

  19. Thiolated poly(aspartic acid) as potential in situ gelling, ocular mucoadhesive drug delivery system.

    PubMed

    Horvát, Gabriella; Gyarmati, Benjámin; Berkó, Szilvia; Szabó-Révész, Piroska; Szilágyi, Barnabás Áron; Szilágyi, András; Soós, Judit; Sandri, Giuseppina; Bonferoni, Maria Cristina; Rossi, Silvia; Ferrari, Franca; Caramella, Carla; Csányi, Erzsébet; Budai-Szűcs, Mária

    2015-01-25

    The ophthalmic formulations on the market suffer from poor bioavailability, and it would therefore be useful to design a new formulation which is able to prolong the residence time and reduce the administration frequency. Polymer matrices which exhibit strong mucoadhesion are promising platforms in ocular drug delivery from the aspect of improved bioavailability. In the present study, an in situ gelling, mucoadhesive drug delivery system was fabricated from thiolated poly(aspartic acid) (ThioPASP). The thiol groups of ThioPASP are able to form disulphide linkages with the mucin glycoproteins and prolong the residence time on the eye. The effects of the thiol groups on the structure, swelling behaviour and mucoadhesive character of the gel and on the drug release profile were determined. The gel structure was characterized by means of rheology. The ThioPASP gel was demonstrated by rheology, tensile test and 'wash away' measurements to display strong mucoadhesion. The drug release from the ThioPASP gel was studied on a vertical Franz diffusion cell: a burst release of sodium diclofenac occurred in the first hour, followed by sustained release of the encapsulated drug for up to 24h. The results proved the importance of the presence of the thiol groups and suggested that a ThioPASP formulation can be useful as an in situ gelling, ocular dosage form. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. A review on mucoadhesive polymer used in nasal drug delivery system

    PubMed Central

    Chaturvedi, Mayank; Kumar, Manish; Pathak, Kamla

    2011-01-01

    This update review is on mucoadhesive polymers used in nasal dosage forms. The nasal mucosa provides a potentially good route for systemic drug delivery. One of the most important features of the nasal route is that it avoids first-pass hepatic metabolism, thereby reducing metabolism. The application of mucoadhesive polymers in nasal drug delivery systems has gained to promote dosage form residence time in the nasal cavity as well as improving intimacy of contact with absorptive membranes of the biological system. The various new technology uses in development of nasal drug delivery dosage forms are discussed. The various dosage forms are vesicular carriers (liposome, noisome), nanostructured particles, prodrugs, in situ gelling system with special attention to in vivo studies. PMID:22247888

  1. Molecular Aspects of Mucoadhesive Carrier Development for Drug Delivery and Improved Absorption

    PubMed Central

    Peppas, Nicholas A; Thomas, J. Brock; McGinity, James

    2011-01-01

    Although the oral route remains the most favored route of drug administration, major scientific obstacles prevent the effective and efficient delivery of low-molecular-mass drugs, peptides and proteins that exhibit poor solubility and permeability. Mucoadhesive dosage forms and the associated drug carriers have the ability to interact at a molecular level with the mucus gel layer that lines the epithelial surfaces of the major absorptive regions of the body. This interaction provides an increased residence time of the therapeutic formulation while localizing the drug at the site of administration. Such local, non-specific targeting leads to an increase in both oral absorption and bioavailability. Fundamental understanding of the biological processes encountered along the gastrointestinal tract can provide a sufficient engineer of carriers that are capable to provide this increase in residence time. Here we discuss the theoretical framework for achieving mucoadhesive systems as related to biomaterials science and the structure of the biomaterials used. PMID:19105897

  2. Development and optimization of thiolated dendrimer as a viable mucoadhesive excipient for the controlled drug delivery: an acyclovir model formulation.

    PubMed

    Yandrapu, Sarath K; Kanujia, Parijat; Chalasani, Kishore B; Mangamoori, Lakshminarasu; Kolapalli, Ramanamurthy V; Chauhan, Abhay

    2013-05-01

    In the present study we report the development of novel thiolated dendrimers for mucoadhesive drug delivery. The thiolated dendrimers were synthesized by conjugating PAMAM dendrimer (G3.5)with cysteamine at two different molar ratios, i.e. 1:30 (DCys1) and 1:60 (DCys2). The thiolated dendrimers were further encapsulated with acyclovir (DCys1Ac and DCys2Ac) and the conjugates were characterized for thiol content, drug loading, drug release, and mucoadhesive behavior. The thiolated dendrimer conjugates showed thiol content of 10.56 ± 0.34 and 68.21 ± 1.84 μM/mg of the conjugate for DCys1 and DCys2, respectively. The acyclovir loading was observed to be highest in dendrimer drug conjugate (DAc) compared to other DCys1Ac and DCys2Ac conjugates. The thiolated dendrimers showed sustained release of acyclovir and showed higher mucoadhesion. The in vitro mucoadhesive activity of DCys2Ac was 1.53 and 2.89 fold higher mucoadhesion compared to DCys1Ac and DAc, respectively. These results demonstrated the usefulness of thiolated dendrimers as a mucoadhesive carrier and represent a novel platform for drug delivery. This study demonstrates the utility of thiolated dendrimers as mucoadhesive carriers as reported in an acyclovir delivery model system. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Physics of drug delivery: dielectric spectroscopy to probe mucoadhesion

    NASA Astrophysics Data System (ADS)

    Stromme, Maria

    2003-04-01

    This work presents how dielectric spectroscopy can be used as a tool to obtain insight about properties on the nano-scale of interfaces of pharmaceutical interest. An outline for studying the adhesion in terms of a compatibility factor between pharmaceutical gels and biological tissue is put forward. The proposed compatibility factor is calculated from the high frequency response (kHz region) of the gel and porcine nasal mucosa separately, and from that of the combined system. It gives an assessment of the possibilities of intimate surface contact, which is generally considered to be the first step in the mucoadhesion process. The results from dielectric spectroscopy were compared to measurements using a tensile strength method and it was found that the gels with the highest compatibility factors were the same as those pointed out as having the highest mucoadhesion using the tensile strength method.

  4. Design of sterile mucoadhesive hydrogels for use in drug delivery: effect of radiation on network structure.

    PubMed

    Singh, Baljit; Varshney, Lalit; Sharma, Vikrant

    2014-09-01

    Radiation induced graft copolymerization is pure, sterile and additive free method for the synthesis of hydrogels for biomedical applications. In the present work, attempt has been made to prepare the biocompatible, mucoadhesive hydrogels based on natural polysaccharide sterculia gum and polyvinylpyrrolidone (PVP) for use as drug delivery devices. The effect of gamma radiation on swelling and various network parameters of hydrogels such as the polymer volume fraction in the swollen state (ϕ), molecular weight of the polymer chain between two neighboring cross links (M¯c), crosslink density (ρ), and mesh size (ξ) have been studied. Hydrogels have been characterized with scanning electron micrographs (SEMs), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction study (XRD), thermo gravimetric analysis (TGA) and swelling studies. Swelling and mesh size decreased while gel strength and crosslink density increased with increase in radiation dose. The swelling of hydrogels and release of drug ciprofloxacin from drug loaded hydrogels occurred through non-Fickian diffusion mechanism. These hydrogels have been observed to have non-thrombogenic, haemo-compatible and mucoadhesive nature and could be used as mucoadhesive drug delivery system to deliver drug to gastro intestinal tract (GIT) in controlled manner.

  5. Development of mucoadhesive dosage forms of buprenorphine for sublingual drug delivery.

    PubMed

    Das, Nandita G; Das, Sudip K

    2004-01-01

    The development of mucoadhesive formulations of buprenorphine for intended sublingual usage in the treatment of drug addiction is described. The formulations include mucoadhesive polymer films, with or without plasticizers, and mucoadhesive polymer tablets, with or without excipients that enhance drug release and/or improve tablet compaction properties. The mucoadhesive polymers studied include carbomers such as Carbopol 934P, Carbopol 974P, and the polycarbophil Noveon AA-1, with excipients chosen from pregelatinized starch, lactose, glycerol, propylene glycol, and various molecular weights of polyethylene glycol. The development of plasticizer-containing mucoadhesive polymer films was feasible; however, these films failed to release their entire drug content within a reasonable period. Thus, they were not determined suitable for sublingual usage because of possible loss by ingestion during routine meal intakes. The mucoadhesive strength of tablet formulations containing Noveon AA-1 appears to be slightly superior to the Carbopol-containing tablets. However, the Carbopol 974P formulations exhibited superior drug dissolution profiles while providing adequate mucoadhesive strength. The tablet formulations containing Carbopol 974P as mucoadhesive polymer, lactose as drug release enhancer, and PEG 3350 as compaction enhancer exhibited the best results. Overall, the mucoadhesive tablet formulations exhibited superior results compared with the mucoadhesive film formulations.

  6. Mucoadhesive drug carrier based on functional-modified cellulose as poorly water-soluble drug delivery system.

    PubMed

    Songsurang, Kultida; Siraleartmukul, Krisana; Muangsin, Nongnuj

    2015-01-01

    The purpose of this study was to design and characterise an oral mucoadhesive micellar drug carrier. In this regard, a mucoadhesive hydrophobic cationic aminocellulose was easily synthesised under mild homogeneous conditions with high yield. The cellulose derivative resulted in strongly improved mucoadhesive properties but was pH dependent. Furthermore, the hydrophobic anticancer drug camptothecin was successfully encapsulated into the mucoadhesive cellulose derivative micelles with spherical shape stability of 233 nm in diameter and low particle size distribution. The CPT-loaded nanocarriers provided high encapsulation efficiency about 86.4%. In vitro release, CPT-loaded cellulose derivative micelles showed a reduction in release rate compared with physically pure CPT solution. The release results also indicated that a sustained release of CPT to >80% over 4 d for pH 6.8 and 7.4. Therefore, mucoadhesive hydrophobic cationic aminocellulose micelles seem to be a promising carrier for various pharmaceutical applications especially for poorly water-soluble drug delivery system.

  7. Whey protein mucoadhesive properties for oral drug delivery: Mucin-whey protein interaction and mucoadhesive bond strength.

    PubMed

    Hsein, Hassana; Garrait, Ghislain; Beyssac, Eric; Hoffart, Valérie

    2015-12-01

    Whey protein is a natural polymer recently used as an excipient in buccoadhesive tablets but its mucoadhesive properties were barely studied. In this work, we characterize mucoadhesion of whey protein in order to determine the mechanisms and optimal conditions for use as excipient in oral drug delivery. Thus, native and denatured whey protein (NWP and DWP) were investigated and the effect of concentration and pH were also studied. Many methods of characterization were selected to allow the study of chemical and physical interactions with mucin and then the results were bound with an ex vivo experiments. Turbidity of WP-mucin mixture increased at acidic pH 1.2 till 4.5 indicating interaction with mucin but not at pH 6.8. No interaction with mucin was also found by ITC method at pH 6.8 for native and denatured whey protein used at 1% (w/w). Forces of bioadhesion evaluated by viscosity measurements were the best for high concentrated (10.8%) DWP solutions at pH 6.8 and were low at pH 1.2 for NWP and DWP solutions. Addition of chemical blockers indicated that hydrogen bondings and disulfide bridges were the main mechanisms of interactions with mucin. Reticulation of DWP with calcium ions to obtain microparticles (MP) did not influence the ability of interaction with mucin as shown by FTIR analysis. These results correlated with ex vivo study on rat tissue demonstrating important adhesion (75%) of WP MP on the intestine and null on the stomach after 2h of deposit.

  8. Genipin-crosslinked catechol-chitosan mucoadhesive hydrogels for buccal drug delivery.

    PubMed

    Xu, Jinke; Strandman, Satu; Zhu, Julian X X; Barralet, Jake; Cerruti, Marta

    2015-01-01

    Drug administration via buccal mucosa is an attractive drug delivery strategy due to good patient compliance, prolonged localized drug effect, and avoidance of gastrointestinal drug metabolism and first-pass elimination. Buccal drug delivery systems need to maintain an intimate contact with the mucosa lining in the wet conditions of the oral cavity for long enough to allow drug release and absorption. For decades, mucoadhesive polymers such as chitosan (CS) and its derivatives have been explored to achieve this. In this study, inspired by the excellent wet adhesion of marine mussel adhesive protein, we developed a buccal drug delivery system using a novel catechol-functionalized CS (Cat-CS) hydrogel. We covalently bonded catechol functional groups to the backbone of CS, and crosslinked the polymer with a non-toxic crosslinker genipin (GP). We achieved two degrees of catechol conjugation (9% and 19%), forming Cat9-CS/GP and Cat19-CS/GP hydrogels, respectively. We confirmed covalent bond formation during the catechol functionalization and GP crosslinking during the gel formation. The gelation time and the mechanical properties of Cat-CS hydrogels are similar to those of CS only hydrogels. Catechol groups significantly enhanced mucoadhesion in vitro (7 out of the 10 Cat19-CS hydrogels were still in contact with porcine mucosal membrane after 6 h, whereas all of the CS hydrogels lost contact after 1.5 h). The new hydrogel systems sustained the release of lidocaine for about 3 h. In-vivo, we compared buccal patches made of Cat19-CS/GP and CS/GP adhered to rabbit buccal mucosa. We were able to detect lidocaine in the rabbit's serum at concentration about 1 ng/ml only from the Cat19-CS patch, most likely due to the intimate contact provided by mucoadhesive Cat19-CS/GP systems. No inflammation was observed on the buccal tissue in contact with any of the patches tested. These results show that the proposed catechol-modified CS hydrogel is a promising mucoadhesive and

  9. Evaluating the mucoadhesive properties of drug delivery systems based on hydrated thiolated alginate.

    PubMed

    Davidovich-Pinhas, Maya; Harari, Offer; Bianco-Peled, Havazelet

    2009-05-21

    Mucoadhesive polymers have been proposed as drug delivery carriers due to their ability to adhere to the mucus layer. A relatively new class of mucoadhesive polymers, termed thiomers, was suggested as an improved carrier capable of creating disulfide covalent bond with the mucus. Since the wet physiological environment is likely to cause any delivery system to adsorb water and arrive hydrated to its target, studying the performance of mucoadhesive systems in their hydrated form is of major importance. Model thiomer, alginate-thiol, were synthesized and characterized the product using Nuclear Magnetic Resonance (NMR), Fourier Transform Infra Red spectroscopy (FTIR). The swelling behavior was determined gravimetrically and found to be affected from the thiolation. Interactions between the alginate-thiol and mucin glycoproteins, which are believed to be an outcome of disulfide bonds, were verified using rheology experiments. Adhesion of hydrated tablets with different cross linking densities to porcine's fresh small intestine tissue were characterized using a Lloyd Tensile Machine. It was shown that the thiolation did not improve the adhesion properties of hydrated tablets. It appears that the benefit achieved by adding thiol group to the polymer in dry tablet form was flawed in hydrated form due to formation of inter-molecular disulfide junctions.

  10. Mucoadhesive effect of thiolated PEG stearate and its modified NLC for ocular drug delivery.

    PubMed

    Shen, Jie; Wang, Yu; Ping, Qineng; Xiao, Yanyu; Huang, Xin

    2009-08-04

    This study was to develop a thiolated non-ionic surfactant, cysteine-polyethylene glycol stearate (Cys-PEG-SA), for the assembling of nanoparticulate ocular drug delivery system with mucoadhesive property. Cys-PEG-SA was synthesized in two steps reaction involving a new derivative intermediate formation of p-nitrophenylcarbonyl-PEG-SA (pNP-PEG-SA). Up to 369.43+/-25.54 mumol free thiol groups per gram of the conjugates was reached. The nanostructured lipid carrier (NLC) loaded cyclosporine A (CyA) was prepared by melt-emulsification method. The mucoadhesive NLC (Cys-NLC) was obtained by incubating NLC emulsion with Cys-PEG-SA. The mucoadhesive properties of these nanocarriers were examined by using mucin particles method. The particle size or zeta potential of the porcine mucin particles were changed with the added concentration of Cys-PEG-SA, and the disulphide bond breaker cysteine significantly reduced the adhesion of Cys-NLC to mucin particles (P<0.05), whereas PEG-SA and NLC did not alternate the properties of the mucin particles. When Cys-NLC was administered topically to the rabbit eye, the encapsulated cyclosporine was found to remain on the ocular surface in the cul-de-sac for up to 6 h, both precorneal retention time and concentration were dramatically increased (P<0.05), compared with the NLC without thiomer modification.

  11. The Potential of Silk and Silk-Like Proteins as Natural Mucoadhesive Biopolymers for Controlled Drug Delivery

    PubMed Central

    Brooks, Amanda E.

    2015-01-01

    Drug delivery across mucus membranes is a particularly effective route of administration due to the large surface area. However, the unique environment present at the mucosa necessitates altered drug formulations designed to (1) deliver sensitive biologic molecules, (2) promote intimate contact between the mucosa and the drug, and (3) prolong the drug's local residence time. Thus, the pharmaceutical industry has an interest in drug delivery systems formulated around the use of mucoadhesive polymers. Mucoadhesive polymers, both synthetic and biological, have a history of use in local drug delivery. Prominently featured in the literature are chitosan, alginate, and cellulose derivatives. More recently, silk and silk-like derivatives have been explored for their potential as mucoadhesive polymers. Both silkworms and spiders produce sticky silk-like glue substances, sericin and aggregate silk respectively, that may prove an effective, natural matrix for drug delivery to the mucosa. This mini review will explore the potential of silk and silk-like derivatives as a biocompatible mucoadhesive polymer matrix for local controlled drug delivery. PMID:26636069

  12. The Potential of Silk and Silk-Like Proteins as Natural Mucoadhesive Biopolymers for Controlled Drug Delivery.

    PubMed

    Brooks, Amanda E

    2015-01-01

    Drug delivery across mucus membranes is a particularly effective route of administration due to the large surface area. However, the unique environment present at the mucosa necessitates altered drug formulations designed to (1) deliver sensitive biologic molecules, (2) promote intimate contact between the mucosa and the drug, and (3) prolong the drug's local residence time. Thus, the pharmaceutical industry has an interest in drug delivery systems formulated around the use of mucoadhesive polymers. Mucoadhesive polymers, both synthetic and biological, have a history of use in local drug delivery. Prominently featured in the literature are chitosan, alginate, and cellulose derivatives. More recently, silk and silk-like derivatives have been explored for their potential as mucoadhesive polymers. Both silkworms and spiders produce sticky silk-like glue substances, sericin and aggregate silk respectively, that may prove an effective, natural matrix for drug delivery to the mucosa. This mini review will explore the potential of silk and silk-like derivatives as a biocompatible mucoadhesive polymer matrix for local controlled drug delivery.

  13. The potential of silk and silk-like proteins as natural mucoadhesive biopolymers for controlled drug delivery

    NASA Astrophysics Data System (ADS)

    Brooks, Amanda

    2015-11-01

    Drug delivery across mucus membranes is a particularly effective route of administration due to the large surface area. However, the unique environment present at the mucosa necessitates altered drug formulations designed to (1) deliver sensitive biologic molecules, (2) promote intimate contact between the mucosa and the drug, and (3) prolong the drug’s local residence time. Thus, the pharmaceutical industry has an interest in drug delivery systems formulated around the use of mucoadhesive polymers. Mucoadhesive polymers, both synthetic and biological, have a history of use in local drug delivery. Prominently featured in the literature are chitosan, alginate, and cellulose derivatives. More recently, silk and silk-like derivatives have been explored for their potential as mucoadhesive polymers. Both silkworms and spiders produce sticky silk-like glue substances, sericin and aggregate silk respectively, that may prove an effective, natural matrix for drug delivery to the mucosa. This mini review will explore the potential of silk and silk-like derivatives as a biocompatible mucoadhesive polymer matrix for local controlled drug delivery.

  14. Mucoadhesive cellulosic derivative sponges as drug delivery system for vaginal application.

    PubMed

    Furst, Tania; Piette, Marie; Lechanteur, Anna; Evrard, Brigitte; Piel, Géraldine

    2015-09-01

    Vaginal delivery of active drugs has been largely studied for local and systemic applications. It is well known that vagina is a complex route, due to physiological and non-physiological changes. Therefore, in order to achieve a prolonged local effect, these variations have to be considered. The aim of this study was to formulate and to characterize a solid system, called sponges, obtained by lyophilization of cellulosic derivative (HEC 250M) hydrogels. These sponges have to meet particular criteria to be adapted for vaginal application: they have to adhere to the vaginal cavity and to be rehydrated by the small amount of vaginal fluids. Moreover, they have to be easily manipulated and to be stable. Three freezing temperatures have been tested to prepare sponges (-15°C, -25°C, -35°C). By SEM analyzes, it was observed that the pores into the sponges were smaller and numerous as the freezing temperature decreases. However, this temperature did not have any influence on the rehydration speed that was rather influenced by the HEC concentration. Viscosity and mucoadhesive strength of hydrogels and corresponding sponges were also measured. It appeared that these parameters are mainly dependent on the HEC concentration. These mucoadhesive sponges can be considered as potential drug delivery systems intended for vaginal application.

  15. In vivo determination of the time and location of mucoadhesive drug delivery systems disintegration in the gastrointestinal tract.

    PubMed

    Kremser, Christian; Albrecht, Karin; Greindl, Melanie; Wolf, Christian; Debbage, Paul; Bernkop-Schnürch, Andreas

    2008-06-01

    The objective of this study was to use magnetic resonance imaging (MRI) to detect the time when and the location at which orally delivered mucoadhesive drugs are released. Drug delivery systems comprising tablets or capsules containing a mucoadhesive polymer were designed to deliver the polymer to the intestine in dry powder form. Dry Gd-DTPA [diethylenetriaminepentaacetic acid gadolinium(III) dihydrogen salt hydrate] powder was added to the mucoadhesive polymer, resulting in a susceptibility artifact that allows tracking of the application forms before their disintegration and that gives a strong positive signal on disintegration. Experiments were performed with rats using T(1)-weighted spin-echo imaging on a standard 1.5-T MRI system. The susceptibility artifact produced by the dry Gd-DTPA powder in tablets or capsules was clearly visible within the stomach of the rats and could be followed during movement towards the intestine. Upon disintegration, a strong positive signal was unambiguously observed. The time between ingestion and observation of a positive signal was significantly different for different application forms. Quantification of the remaining mucoadhesive polymer in the intestine 3 h after observed release showed significant differences in mucoadhesive effectiveness. MRI allows detection of the exact time of release of the mucoadhesive polymer in vivo, which is a prerequisite for a reliable quantitative comparison between different application forms.

  16. Mucoadhesive Chitosan–Dextran Sulfate Nanoparticles for Sustained Drug Delivery to the Ocular Surface

    PubMed Central

    Chaiyasan, Wanachat; Srinivas, Sangly P.

    2013-01-01

    Abstract Purpose To characterize nanoparticles produced by self-assembly of oppositely charged polymers, cationic chitosan (CS), and anionic dextran sulfate (DS), for drug delivery to the ocular surface. The goal is to overcome the short residence time of topical drugs through their sustained release from mucoadhesive nanoparticles. Methods Chitosan–dextran sulfate nanoparticles (CDNs) were produced by mixing CS and DS; polyethylene glycol-400 was used as a surface stabilizing agent. Fourier transform infrared spectroscopy (FTIR) spectra of CS, DS, and CDNs were determined in the wavenumber range of 4,000–700 cm−1 to assess the ionic interactions in the formation of CDNs. The physicochemical properties, entrapment efficacy, and dissolution profile of CDNs were investigated using Rhodamine B (RhB) and Nile Red (NR) as drug analogs. The mucoadhesiveness of the CDNs was assessed by imaging the retention of the fluorescein isothiocyanate-labeled CDNs on the cornea ex vivo, which was subjected to shear stress by a steady stream of saline solution. Results CDNs were obtained by the polyelectrolyte complexation technique. The FTIR spectra of CDNs showed spectral shifts in the amine and sulfate regions, confirming an involvement of electrostatic interactions between cationic CS and anionic DS. The CDNs were spherical in shape and segregated. They possessed a particle size of ∼400 nm with a polydispersity index of 0.3 and exhibited a zeta potential of ∼40 mV. A high entrapment efficacy of up to 80% was observed with both RhB and NR. In the dissolution experiments, NR was released from CDNs within 60 min, but RhB was not released. This indicates that the release of drugs could depend on their molecular interactions with the particle. Exposure of CDNs to lysozyme, which is found in tears, had no effect on the mean particle size or the surface charge. Instillation of NR, RhB, and FITC in the presence of saline irrigation resulted in their rapid disappearance

  17. Design, formulation and evaluation of a mucoadhesive gel from Quercus brantii L. and coriandrum sativum L. as periodontal drug delivery

    PubMed Central

    Aslani, Abolfazl; Ghannadi, Alireza; Najafi, Hajar

    2013-01-01

    Background: Periodontitis is inflammation of the supporting tissues of the teeth caused by specific microorganisms. Intra-periodontal pocket, mucoadhesive drug delivery systems have been shown to be clinically effective in the treatment of periodontitis. The aim of this study was to formulate a mucoadhesive gel from the seed hull of Quercus brantii and fruits of Coriandrum sativum for the treatment of periodontitis. Materials and Methods: The semisolid concentrated extracts were incorporated in gel base. Mucoadhesive gels were prepared using carbopol 940, sodium carboxymethylcellulose (sodium CMC) and hydroxypropyl methylcellulose K4M (HPMC) as bioadhesive polymers. Physicochemical tests, mucoadhesive strength measurement and in vitro drug release study were carried out on two formulations containing carbopol 940 and sodium CMC polymers (Formulations F4 and F5). We investigated the antibacterial activity of formulation F5 against Porphyromonas gingivalis using the disk diffusion method on supplemented Brucella agar. Results: Eight gel formulations were prepared. Physical appearance, homogeneity and consistency of F4 and F5 were good. Mucoadhesion and viscosity of F5 (1% carbopol 940 and 3% sodium CMC) was more than F4 (0.5% carbopol 940 and 3% sodium CMC). Drug release from F5 was slower. Both of formulations were syringeable through 21 G needle. In the disk diffusion method, F5 produced significant growth inhibition zones against P. gingivalis. Conclusion: The ideal formulation for the treatment of periodontitis should exhibit high value of mucoadhesion, show controlled release of drug and be easily delivered into the periodontal pocket preferably using a syringe. Based on in vitro release and mucoadhesion studies, F5 was selected as the best formulation. PMID:23977649

  18. Design, formulation and evaluation of a mucoadhesive gel from Quercus brantii L. and coriandrum sativum L. as periodontal drug delivery.

    PubMed

    Aslani, Abolfazl; Ghannadi, Alireza; Najafi, Hajar

    2013-01-01

    Periodontitis is inflammation of the supporting tissues of the teeth caused by specific microorganisms. Intra-periodontal pocket, mucoadhesive drug delivery systems have been shown to be clinically effective in the treatment of periodontitis. The aim of this study was to formulate a mucoadhesive gel from the seed hull of Quercus brantii and fruits of Coriandrum sativum for the treatment of periodontitis. The semisolid concentrated extracts were incorporated in gel base. Mucoadhesive gels were prepared using carbopol 940, sodium carboxymethylcellulose (sodium CMC) and hydroxypropyl methylcellulose K4M (HPMC) as bioadhesive polymers. Physicochemical tests, mucoadhesive strength measurement and in vitro drug release study were carried out on two formulations containing carbopol 940 and sodium CMC polymers (Formulations F4 and F5). We investigated the antibacterial activity of formulation F5 against Porphyromonas gingivalis using the disk diffusion method on supplemented Brucella agar. Eight gel formulations were prepared. Physical appearance, homogeneity and consistency of F4 and F5 were good. Mucoadhesion and viscosity of F5 (1% carbopol 940 and 3% sodium CMC) was more than F4 (0.5% carbopol 940 and 3% sodium CMC). Drug release from F5 was slower. Both of formulations were syringeable through 21 G needle. In the disk diffusion method, F5 produced significant growth inhibition zones against P. gingivalis. The ideal formulation for the treatment of periodontitis should exhibit high value of mucoadhesion, show controlled release of drug and be easily delivered into the periodontal pocket preferably using a syringe. Based on in vitro release and mucoadhesion studies, F5 was selected as the best formulation.

  19. Drug permeability and mucoadhesion properties of thiolated trimethyl chitosan nanoparticles in oral insulin delivery.

    PubMed

    Yin, Lichen; Ding, Jieying; He, Chunbai; Cui, Liming; Tang, Cui; Yin, Chunhua

    2009-10-01

    Trimethyl chitosan-cysteine conjugate (TMC-Cys) was synthesized in an attempt to combine the mucoadhesion and the permeation enhancing effects of TMC and thiolated polymers related to different mechanisms for oral absorption. TMC-Cys with various molecular weights (30, 200, and 500 kDa) and quaternization degrees (15 and 30%) was allowed to form polyelectrolyte nanoparticles with insulin through self-assembly, which demonstrated particle size of 100-200 nm, zeta potential of +12 to +18 mV, and high encapsulation efficiency. TMC-Cys/insulin nanoparticles (TMC-Cys NP) showed a 2.1-4.7-fold increase in mucoadhesion compared to TMC/insulin nanoparticles (TMC NP), which might be partly attributed to disulfide formation between TMC-Cys and mucin as evidenced by DSC measurement. Compared to insulin solution and TMC NP, TMC-Cys NP induced increased insulin transport through rat intestine by 3.3-11.7 and 1.7-2.6 folds, promoted Caco-2 cell internalization by 7.5-12.7 and 1.7-3.0 folds, and augmented uptake in Peyer's patches by 14.7-20.9 and 1.7-5.0 folds, respectively. Such results were further confirmed by in vivo experiment with the optimal TMC-Cys NP. Biocompatibility assessment revealed lack of toxicity of TMC-Cys NP. Therefore, self-assembled nanoparticles between TMC-Cys and protein drugs could be an effective and safe oral delivery system.

  20. In vitro evaluation of the mucoadhesive properties of polysaccharide-based nanoparticulate oral drug delivery systems.

    PubMed

    Chayed, Siwar; Winnik, Françoise M

    2007-03-01

    Impedance quartz crystal microbalance (QCM) and surface plasmon resonance (SPR) measurements were performed in order to assess the mucoadhesive properties of hydrophobically modified (HM) derivatives of dextran (DEX), with an average molecular weight of 10,000 Da, and of hydroxypropylcellulose (HPC), with an average molecular weight of 80,000 Da. The measurements involved (1) treatment of a hydrophobic surface with bovine submaxillary gland mucin (BSM) under various pH conditions (2.0-8.0) and (2) treatment of the BSM layer with buffer solutions of the amphiphilic polysaccharides (pH 3.0 and 7.0). Control measurements were carried out with DEX, HPC, and chitosan (CH) used as a model mucoadhesive polymer. All HM-polysaccharides were shown to adsorb onto a BSM layer, the extent of adsorption increasing with increasing hydrophobicity of the samples. Under the same conditions, HPC and CH interacted with the BSM layer, but DEX showed no affinity to BSM. All the results suggest that HM-polysaccharide micellar systems have the potential of enhancing the bioavailability of poorly adsorbed drugs in peroral delivery.

  1. Mucoadhesive nanoemulsion-based intranasal drug delivery system of olanzapine for brain targeting.

    PubMed

    Kumar, Mukesh; Misra, Ambikanandan; Mishra, A K; Mishra, Pushpa; Pathak, Kamla

    2008-12-01

    The objective of the present study was to optimize olanzapine nanoemulsion (ONE), for nose-to-brain delivery. The nanoemulsions and olanzapine mucoadhesive nanoemulsions (OMNEs) were prepared using water titration method and characterized for technical and electrokinetic properties. Biodistribution of nanoemulsions and olanzapine solution (OS) in the brain and blood of rats following intranasal (intranasal) and intravenous (intravenous) administrations were examined using optimized technetium-labeled ((99m)Tc-labeled) olanzapine formulations. The brain/blood uptake ratios of 0.45, 0.88, 0.80, and 0.04 of OS (intranasal), ONE (intranasal), OMNE (intranasal), ONE (intravenous), respectively, at 0.5 h are indicative of direct nose-to-brain transport (DTP). Higher % drug targeting efficiency (%DTE) and %DTP for mucoadhesive nanoemulsions indicated effective brain targeting of olanzapine among the prepared nanoemulsions. Gamma scintigraphy imaging of the rat brain conclusively demonstrated rapid and larger extent of transport of olanzapine by OMNE (intranasal), when compared with OS (intranasal), ONE (intranasal), and ONE (intravenous), into the rat brain.

  2. An overview of recent patents on composition of mucoadhesive drug delivery systems.

    PubMed

    Bruschi, Marcos L; de Francisco, Lizziane M B; S de Toledo, Lucas de Alcantara; Borghi, Fernanda B

    2015-01-01

    Mucoadhesion began to be applied to therapeutic systems with the aim of the incorporation of bioadhesive molecules into pharmaceutical dosage forms intended to keep in close contact with the tissue, releasing the drug near the action site, thereby increasing its bioavailability and promoting local or systemic effects. Different mucoadhesive materials and dosage forms have been studied, since the properties of mucoadhesion largely depend on the features of the material used in its preparation. This mini-review focuses on mucoadhesive therapeutic systems, the main mucosal routes of administration, and materials used to prepare the systems over the last five years. Patents and applications were reviewed, categorized and the materials were described together with the proposed systems.

  3. Mucoadhesive microparticulate drug delivery system of curcumin against Helicobacter pylori infection: Design, development and optimization

    PubMed Central

    Ali, Mohd Sajid; Pandit, Vinay; Jain, Mahendra; Dhar, Kanhiya Lal

    2014-01-01

    The purpose of the present research was to develop and characterize mucoadhesive microspheres of curcumin for the potential use of treating gastric adenocarcinoma, gastric and duodenal ulcer associated with Helicobacter pylori. Curcumin mucoadhesive microspheres were prepared using ethyl cellulose as a matrix and carbopol 934P as a mucoadhesive polymer by an emulsion-solvent evaporation technique. Response surface methodology was used for optimization of formulation using central composite design (CCD) for two factors at three levels each was employed to study the effect of independent variables, drug:polymer:polymer ratio (curcumin:ethylcellulose:carbopol 934P)(X1) and surfactant concentration (X2) on dependent variables, namely drug entrapment efficiency (DEE), percentage mucoadhesion (PM), in vitro drug release and particle size (PS). Optimized formulation was obtained using desirability approach of numerical optimization. The experimental values of DEE, PM, % release and PS after 8 h for the optimized formulation were found to be 50.256 ± 1.38%, 66.23%±0.06, 73.564 ± 1.32%, and 139.881 ± 2.56 μm, respectively, which were in close agreement with those predicted by the mathematical models. The drug release was also found to be slow and extended more than 8 h and release rates were fitted to the Power law equation and Higuchi model to compute the diffusional parameters. The prolonged stomach residence time of curcumin mucoadhesive microspheres might make a contribution to H. pylori complete eradication in combination with other antimicrobial agents. PMID:24696817

  4. Mucoadhesive thiolated chitosans as platforms for oral controlled drug delivery: synthesis and in vitro evaluation.

    PubMed

    Roldo, Marta; Hornof, Margit; Caliceti, Paolo; Bernkop-Schnürch, Andreas

    2004-01-01

    The aim of the present study was to evaluate the influence of the degree of modification and the polymer chain length on the mucoadhesive properties and the swelling behavior of thiolated chitosan derivatives obtained via a simple one-step reaction between the polymer and 2-iminothiolane. The conjugates differing in molecular mass of the polymer backbone and in the amount of immobilized thiol groups were compressed into tablets. They were investigated for their mucoadhesive properties on freshly excised porcine mucosa via tensile studies and the rotating cylinder method. Moreover, the swelling behavior of these tablets in aqueous solutions was studied by a simple gravimetric method. The obtained results demonstrated that the total work of adhesion of chitosan-TBA (=4-thio-butyl-amidine) conjugates can be improved by an increasing number of covalently attached thiol groups; a 100-fold increase compared to unmodified chitosan was observed for a medium molecular mass chitosan-TBA conjugate exhibiting 264 microM thiol groups per gram polymer. Also, the polymer chain length had an influence on the mucoadhesive properties of the polymer. The medium molecular mass polymer displayed a fourfold improved adhesion on the rotating cylinder compared to the derivative of low molecular mass. These results contribute to the development of new delivery systems exhibiting improved mucoadhesive properties.

  5. A novel approach to enhance the mucoadhesion of lipid drug nanocarriers for improved drug delivery to the buccal mucosa.

    PubMed

    Du, Joanne D; Liu, Qingtao; Salentinig, Stefan; Nguyen, Tri-Hung; Boyd, Ben J

    2014-08-25

    Targeted drug delivery to the buccal mucosa offers distinct advantages over oral delivery to the gastrointestinal tract including by-passing hepatic first-pass metabolism. However, the buccal route is often limited by low bioavailability, low drug loading and reduced residence time due to salivary excretion and clearance. To overcome these limitations, a novel mucoadhesive formulation based on liquid crystalline nanoparticles was designed. Utilising a pH induced in situ transition from a stable vesicle formulation to dispersed inverse hexagonal phase nanoparticles (hexosomes) enhanced adsorption onto the mucosal surface was enabled. Firstly, the phase behaviour of the amphiphilic lipid phytantriol (PHY) and oleic acid (OA) was assessed from pH 2-9 using small-angle X-ray scattering (SAXS) and cryo-transmission electron microscopy (cryo-TEM) to determine the appropriate composition for the vesicle to hexosome transition. The colloidal stability of the formulation was determined using turbidity studies. Dispersions comprising 30% w/w OA in PHY were able to form stable vesicles at pH 8 and transition to hexosomes when exposed to pH<7 (as encountered on the buccal mucosal surface). Subsequent ex vivo studies utilising excised porcine buccal tissue indicated significant retention of the in situ-formed PHY/OA hexosomes when compared to control DOPC vesicles (p<0.005), confirmed independently using confocal fluorescence microscopy, radioactive scintillation counting and HPLC analysis for incorporated drug. Thus, a novel approach providing a stable vesicle formulation, with in situ transformation to mucoadhesive hexosomes has been identified with the potential to enhance drug delivery to mucosal surfaces.

  6. Solid lipid nanoparticles for oral drug delivery: chitosan coating improves stability, controlled delivery, mucoadhesion and cellular uptake.

    PubMed

    Luo, Yangchao; Teng, Zi; Li, Ying; Wang, Qin

    2015-05-20

    The poor stability of solid lipid nanoparticles (SLN) under acidic condition resulted in large aggregation in gastric environment, limiting their application as oral delivery systems. In this study, a series of SLN was prepared to investigate the effects of surfactant/cosurfactant and chitosan coating on their physicochemical properties as well as cellular uptake. SLN was prepared from Compritol 888 ATO using a low-energy method combining the solvent-diffusion and hot homogenization technique. Poloxamer 188 and polyethylene glycol (PEG) were effective emulsifiers to produce SLN with better physicochemical properties than SLN control. Chitosan-coated SLN exhibited the best stability under acidic condition by forming a thick layer around the lipid core, as clearly observed by transmission electron microscope. The intermolecular interactions in different formulations were monitored by Fourier transform infrared spectroscopy. Chitosan coating also significantly improved the mucoadhesive property of SLN as determined by Quartz Crystal Microbalance. In vitro drug delivery assays, cytotoxicity, and cellular uptake of SLN were studied by incorporating coumarin 6 as a fluorescence probe. Overall, chitosan-coated SLN was superior to other formulations and held promising features for its application as a potential oral drug delivery system for hydrophobic drugs.

  7. Development and evaluation of mucoadhesive nanoparticles based on thiolated Eudragit for oral delivery of protein drugs

    NASA Astrophysics Data System (ADS)

    Zhang, Yan; Yang, Zhijie; Hu, Xi; Zhang, Ling; Li, Feng; Li, Meimei; Tang, Xing; Xiao, Wei

    2015-02-01

    The objective of this study was to develop pH-sensitive Eudragit L100-cysteine/reduced glutathione (Eul-cys/GSH) nanoparticles (NPs), which provided the mucoadhesion and protection for protein drugs against enzymatic degradation. Insulin was chosen as a model biomolecule for testing this system. The Eul-cys conjugate, which was obtained by grafting cysteine onto the carboxy group of Eudragit L100, was analyzed by HNMR and SEM, and the swelling degree (SD), cation binding, and enzymatic inhibition were also determined. The results obtained showed that the Eul-cys conjugate represent a pH-sensitive delivery system which effectively protected the insulin from being degraded by the proteases, and this is related to the mechanism of Ca2+ binding. Insulin-loaded Eul-cys/GSH NPs were prepared by a diffusion method involving an electrostatic interaction between the network structure of the polymer and the embedded proteins, including insulin and GSH. TEM images indicated that Eul-cys/GSH existed as smooth and spherical NPs in aqueous solution with particle sizes of 260 ± 20 nm. The X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) findings showed the presence of amorphous insulin in thiolated NPs and higher free thiol oxidation than the result obtained by Ellman's reagent method. In addition, thiolated NPs showed excellent binding efficiency to the mucin in rat intestine, indicating that Eul-cys/GSH NPs have great potential to be applied as safe carriers for the oral administration of protein drugs.

  8. In vitro and in vivo adhesion testing of mucoadhesive drug delivery systems.

    PubMed

    Chary, R B; Vani, G; Rao, Y M

    1999-05-01

    Bioadhesive tablets were prepared by physical mixing of polymers and drug, then granulating and compressing into a tablet. The mucoadhesion was evaluated by shear stress measurement, detachment force measurement, and X-ray photography of the rabbit gastrointestinal tract. The strong interaction between the polymer and the mucous lining of the tissue helps increase contact time and permit localization. Polymers like hydroxypropyl methylcellulose K4M (HPMC K4M), hydroxypropyl methylcellulose 100 cps (HPMC 100 cps), carbopol-934, sodium carboxy methylcellulose (Na CMC), guar gum, and polyvinylpyrrolidone (PVP) were tested by shear stress measurement and detachment force measurement methods. HPMC K4M, showing maximum bioadhesion, was used in further studies. Adhesion was maximum between pH 5 and pH 6. Maximum adhesion was observed in the duodenum, followed by the jejunum and ileum. Barium sulfate (BaSO4) matrix tablets containing polymer and drug were subjected to X-ray studies in rabbits, and it was found that the tablet was mucoadhesive even after 8 hr. Enteric coating did not show any effect on mucoadhesion after passing from the stomach.

  9. Nasal drug delivery: Design of a novel mucoadhesive and in situ gelling polymer.

    PubMed

    Menzel, Claudia; Jelkmann, Max; Laffleur, Flavia; Bernkop-Schnürch, Andreas

    2017-01-30

    The aim of the present study was to establish a novel polymeric excipient for liquid nasal dosage forms exhibiting viscosity increasing properties, improved mucoadhesion and stability towards oxidation in solution. In order to achieve this goal, 2-mercaptonicotinic acid was first coupled to l-cysteine by disulfide exchange reaction and after purification directly attached to the polymeric backbone of xanthan gum by carbodiimide mediated amide bond formation. The resulting conjugate was characterized with respect to the amount of coupled ligand, the in situ gelling behavior, mucoadhesive properties and stability towards oxidation. Furthermore, the influence of preactivated polymers on ciliary beat frequency (CBF) of porcine nasal epithelial cells was investigated. Results showed, that 252.52±20.54μmol of the ligand was attached per gram polymer. No free thiol groups could be detected on the polymeric backbone indicating entire preactivation. Rheological investigations of polymer mucus mixtures revealed a 1.7-fold and 2.5-fold enhanced mucoadhesion of entirely preactivated xanthan (Xan-Cys-MNA) compared to thiolated xanthan (Xan-Cys) and unmodified xanthan (Xan). Tensile force evaluation reported a 2.87 and 5.11-fold higher total work of adhesion (TWA) as well as a 1.63 and 2.41-fold higher maximum detachement force of Xan-Cys-MNA compared to Xan-Cys and Xan. In the presence of H2O2 as an oxidizing agent Xan-Cys-MNA showed unlike Xan-Cys no increase in viscosity, indicating high stability towards oxidation. Addition of CaCl2 to Xan-Cys-MNA solutions caused a decrease in viscosity at nevertheless higher total viscosity. Results from CBF studies proved nasal safety for the novel conjugate. According to these results, entirely preactivated thiolated xanthan gum seems to be a promising excipient for nasal dosage forms in order to improve drug bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Preactivated hyaluronic acid: A potential mucoadhesive polymer for vaginal delivery.

    PubMed

    Nowak, Jessika; Laffleur, Flavia; Bernkop-Schnürch, Andreas

    2015-01-15

    The objective of this study was to develop mucoadhesive polymeric excipients for vaginal drug delivery systems. Hyaluronic acid was thiolated and subsequently preactivated with 6-mercaptonicotinamide (HA-CYS-MNA) to enhance stability and mucoadhesive properties on vaginal mucosa. After determination of the thiol group content, disintegration studies and in vitro mucoadhesion studies (rotating cylinder and tensile) were performed. Furthermore, swelling behavior and cytotoxicity studies were performed in comparison with corresponding polymers. Both, disintegration and in vitro mucoadhesive studies revealed that modifying HA-CYS with MNA resulted in higher stability (3.6-fold prolonged disintegration time compared to unmodified hyaluronic acid) and prolonged mucoadhesion time. MTT assay and LDH revealed no toxicity for the polymeric excipients and safe for their use. Disintegration and swelling results conducted more pronounced stability of the preactivated thiomers compared to corresponding unmodified ones. According to these results preactivated hyaluronic acid might be a useful tool for vaginal delivery systems.

  11. Gastroretentive drug delivery system of acyclovir-loaded alginate mucoadhesive microspheres: formulation and evaluation.

    PubMed

    Shadab; Ahuja, Alka; Khar, Roop K; Baboota, Sanjula; Chuttani, Krishna; Mishra, A K; Ali, Javed

    2011-05-01

    In the present study, mucoadhesive alginate microspheres of acyclovir were prepared to prolong the gastric residence time using a simple emulsification phase separation technique. The particle size of drug-loaded formulations was measured by SEM and the particle size distribution was determined using an optical microscope and mastersizer. The release profile of acyclovir from microspheres was examined in simulated gastric fluid (SGF pH 1.2). The particles were found to be discreet and spherical with the maximum particles of an average size (70.60 ± 2.44 µm). The results indicated that the mean particle size of the microspheres increased with an increase in the concentration of polymer and decreased with increase in stirring speed. The entrapment efficiency was found to be in the range of 51.42-80.46%. The concentration of the calcium chloride (% w/v) of 10% and drug-polymer ratio of 1:4 resulted in an increase in the entrapment efficiency and the extent of drug release. The optimized alginate microspheres were found to possess good mucoadhesion (66.42 ± 1.01%). The best fit model with the highest regression coefficient values (R²) was predicted by Peppas model (0.9813). In Gamma scintigraphy analysis, the section of GIT was critically analyzed and much differentiation was present at each time point after oral administration, which revealed that the optimized formulation demonstrated gastroretention in vivo for more than 4 h, which revealed that optimized formulation could be a good choice for gastroretentive systems.

  12. Surface charge effect on mucoadhesion of chitosan based nanogels for local anti-colorectal cancer drug delivery.

    PubMed

    Feng, Chao; Li, Jing; Kong, Ming; Liu, Ya; Cheng, Xiao Jie; Li, Yang; Park, Hyun Jin; Chen, Xi Guang

    2015-04-01

    To develop more effective anticancer mucoadhesive drug delivery system for the treatment of colorectal cancer, chitosan based nanogels (NGs) were prepared by electrostatic interaction between chitosan (CS) and carboxymethyl-chitosan (CMCS). By respectively using tripolyphosphate (TPP) and CaCl2 as ionic crosslinker, two well-characterized doxorubicin hydrochloride (DOX) loaded NGs with opposite zeta potential (DOX:CS/CMCS/TPP NGs, -32.6±1.1 mV and DOX:CS/CMCS/Ca2+ NGs, +31.8±0.9 mV) were obtained. Compared with DOX:CS/CMCS/TPP NGs, DOX:CS/CMCS/Ca2+ NGs were taken up to a greater extent by colorectal cancer cells, resulting in greater reduction in percentage of cell viability. Owing to high binding capability to mucin and inhibited paracellular transport by colon, DOX:CS/CMCS/Ca2+ NGs exhibited improved mucoadhesion and limited permeability. This is beneficial to prolong the contact time of formulation onto intestinal mucosa and improved local drug concentration. The results provided evidence DOX:CS/CMCS/Ca2+ NGs to be exciting and promising for the treatment of colorectal cancer.

  13. An examination of the rheological and mucoadhesive properties of poly(acrylic acid) organogels designed as platforms for local drug delivery to the oral cavity.

    PubMed

    Jones, David S; Muldoon, Brendan C O; Woolfson, A David; Sanderson, F Dominic

    2007-10-01

    This study examined the rheological/mucoadhesive properties of poly(acrylic acid) PAA organogels as platforms for drug delivery to the oral cavity. Organogels were prepared using PAA (3%, 5%, 10% w/w) dissolved in ethylene glycol (EG), propylene glycol (PG), 1,3-propylene glycol (1,3-PG), 1,5-propanediol (1,5-PD), polyethylene glycol 400 (PEG 400), or glycerol. All organogels exhibited pseudoplastic flow. The increase in storage (G') and loss (G'') moduli of organogels as a function of frequency was minimal, G'' was greater than G'' (at all frequencies), and the loss tangent <1, indicative of gel behavior. Organogels prepared using EG, PG, and 1,3-propanediol (1,3-PD) exhibited similar flow/viscoelastic properties. Enhanced rheological structuring was associated with organogels prepared using glycerol (in particular) and PEG 400 due to their interaction with adjacent carboxylic acid groups on each chain and on adjacent chains. All organogels (with the exception of 1,5-PD) exhibited greater network structure than aqueous PAA gels. Organogel mucoadhesion increased with polymer concentration. Greatest mucoadhesion was associated with glycerol-based formulations, whereas aqueous PAA gels exhibited the lowest mucoadhesion. The enhanced network structure and the excellent mucoadhesive properties of these organogels, both of which may be engineered through choice of polymer concentration/solvent type, may be clinically useful for the delivery of drugs to the oral cavity. (c) 2007 Wiley-Liss, Inc.

  14. Multi-layered nanofibrous mucoadhesive films for buccal and sublingual administration of drug-delivery and vaccination nanoparticles - important step towards effective mucosal vaccines.

    PubMed

    Mašek, Josef; Lubasová, Daniela; Lukáč, Róbert; Turánek-Knotigová, Pavlína; Kulich, Pavel; Plocková, Jana; Mašková, Eliška; Procházka, Lubomír; Koudelka, Štěpán; Sasithorn, Nongnut; Gombos, Jozsef; Bartheldyová, Eliška; Hubatka, František; Raška, Milan; Miller, Andrew D; Turánek, Jaroslav

    2017-03-10

    Nanofibre-based mucoadhesive films were invented for oromucosal administration of nanocarriers used for delivery of drugs and vaccines. The mucoadhesive film consists of an electrospun nanofibrous reservoir layer, a mucoadhesive film layer and a protective backing layer. The mucoadhesive layer is responsible for tight adhesion of the whole system to the oral mucosa after application. The electrospun nanofibrous reservoir layer is intended to act as a reservoir for polymeric and lipid-based nanoparticles, liposomes, virosomes, virus-like particles, dendrimers and the like, plus macromolecular drugs, antigens and/or allergens. The extremely large surface area of nanofibrous reservoir layers allows high levels of nanoparticle loading. Nanoparticles can either be reversibly adsorbed to the surface of nanofibres or they can be deposited in the pores between the nanofibres. After mucosal application, nanofibrous reservoir layers are intended to promote prolonged release of nanoparticles into the submucosal tissue. Reversible adsorption of model nanoparticles as well as sufficient mucoadhesive properties were demonstrated. This novel system appears appropriate for the use in oral mucosa, especially for sublingual and buccal tissues. To prove this concept, trans-/intramucosal and lymph-node delivery of PLGA-PEG nanoparticles was demonstrated in a porcine model. This system can mainly be used for sublingual immunization and the development of "printed vaccine technology".

  15. Transbuccal delivery of betahistine dihydrochloride from mucoadhesive tablets with a unidirectional drug flow: in vitro, ex vivo and in vivo evaluation

    PubMed Central

    El-Nabarawi, Mohamed A; Ali, Adel A; Aboud, Heba M; Hassan, Amira H; Godah, Amany H

    2016-01-01

    Objective Betahistine dihydrochloride (BH.2HCl), an anti-vertigo histamine analog used in the treatment of Ménière’s disease, undergoes extensive first-pass metabolism and suffers from short biological half-life. The aim of the present work was to develop and estimate controlled release mucoadhesive buccal tablets of BH.2HCl with a unidirectional drug flow to overcome this encumbrance. Methods A direct compression method was adopted for preparation of the tablets using mucoadhesive polymers like guar gum, hydroxypropyl methyl cellulose K4M, sodium carboxymethyl cellulose and their combinations. The tablets were coated from all surfaces except one surface with a solution of 5% (w/v) cellulose acetate and 1% (w/v) dibutyl phthalate. Different permeation enhancers like 2% sodium deoxycholate, 2% sodium cholate hydrate (SCH) and 5% menthol were tested. Swelling index, ex vivo residence time, mucoadhesion strength, in vivo testing of mucoadhesion time, in vitro dissolution and ex vivo permeation were carried out. Furthermore, compatibility and accelerated stability studies were performed for the drug excipients. Finally, drug bioavailability of the BH.2HCl-optimized buccal mucoadhesive formulation was compared with that of the orally administered Betaserc® 24 mg tablet in six healthy male volunteers. Results Formulation F10, which contained a combination of 35% guar gum and 5% sodium carboxymethyl cellulose, exhibited long adhesion time, high adhesion strength and diminished irritation to volunteers and showed zero-order release kinetics. SCH produced a significant enhancement in permeation of BH.2HCl across buccal mucosa. BH.2HCl-optimized buccal mucoadhesive formulation showed percentage relative bioavailability of 177%. Conclusion The developed mucoadhesive tablets represent a promising alternative for the buccal delivery of BH.2HCl. PMID:28008227

  16. Mucoadhesive intestinal devices for oral delivery of salmon calcitonin.

    PubMed

    Gupta, Vivek; Hwang, Byeong Hee; Lee, Joohee; Anselmo, Aaron C; Doshi, Nishit; Mitragotri, Samir

    2013-12-28

    One of the major challenges faced by therapeutic polypeptides remains their invasive route of delivery. Oral administration offers a potential alternative to injections; however, this route cannot be currently used for peptides due to their limited stability in the stomach and poor permeation across the intestine. Here, we report mucoadhesive devices for oral delivery that are inspired by the design of transdermal patches and demonstrate their capabilities in vivo for salmon calcitonin (sCT). The mucoadhesive devices were prepared by compressing a polymeric matrix containing carbopol, pectin and sodium carboxymethylcellulose (1:1:2), and were coated on all sides but one with an impermeable and flexible ethyl cellulose (EC) backing layer. Devices were tested for in vitro dissolution, mucoadhesion to intestinal mucosa, enhancement of drug absorption in vitro (Caco-2 monolayer transport) and in vivo in rats. Devices showed steady drug release with ≈75% cumulative drug released in 5h. Devices also demonstrated strong mucoadhesion to porcine small intestine to withstand forces up to 100 times their own weight. sCT-loaded mucoadhesive devices exhibited delivery of sCT across Caco-2 monolayers and across the intestinal epithelium in vivo in rats. A ≈52-fold (pharmacokinetic) and ≈44-fold (pharmacological) enhancement of oral bioavailability was observed with mucoadhesive devices when compared to direct intestinal injections. Oral delivery of devices in enteric coated capsules resulted in significant bioavailability enhancement.

  17. Mucoadhesive patches of Salbutamol sulphate for unidirectional buccal drug delivery: development and evaluation.

    PubMed

    Puratchikody, Ayarivan; Prasanth, V V; Mathew, Sam T; Kumar, B Ashok

    2011-07-01

    Mucoadhesive buccal patches of Salbutamol Sulphate were prepared using five different polymers (polyvinylpyrrolidone [PVP]), polyvinyl alcohol [PVA], water soluble chitosan [CH(WS)], acid soluble chitosan [CH(AS)], hydroxypropyl methyl cellulose [HPMC])in various proportions and combinations (CH(WS)/PVP/HPMC, CH(WS)/PVA/HPMC, CH(AS)/PVP/HPMC, and CH(AS)/PVA/HPMC). A 3(2) full factorial design was used to design the experiments. A total of 72 patches were prepared. Thickness of the patches ranged between 0.3±0.003 and 0.6±0.009 mm. Mass of the patches were in the range of 68.12±4.6 to 95.02±7.2 mg. Patches showed increased mass whenever PEG -400 was used as plasticizer. The surface pH of patches were acidic to neutral (pH 4-pH 7). Patches showed satisfactory drug loading efficiency (85%to 97%). Eight formulations(C9, C18, C27, C36, D9, D18, D27, and D36)-which showed high folding endurance- were selected for further characterization. Patches with PEG -400 showed higher swelling index when compared to PG. The residence time of the patches ranged between 115 min and 120 min. Formulation C18 showed the maximum in vitro drug release of 101.4 % over a period of 120 min. Formulations D36 and C36 were best fitted to Higuchi model. The remaining formulations were best fitted to the Korsmeyer-Peppas model. Drug permeation was fast and showed the similar profile as that of the in vitro drug release. Patches were stable, during and at the end of the accelerated stability study.

  18. Mucoadhesive elementary osmotic pump tablets of trimetazidine for controlled drug delivery and reduced variability in oral bioavailability.

    PubMed

    Alam, Naushad; Beg, Sarwar; Rizwan, Mohammad; Ahmad, Akifa; Ahmad, Farhan Jalees; Ali, Asgar; Aqil, Mohammad

    2015-04-01

    The objectives of this work was preparation and evaluation of the mucoadhesive elementary osmotic pump tablets of trimetazidine hydrochloride to achieve desired controlled release action and augmentation of oral drug absorption. The drug-loaded core tablets were prepared employing the suitable tableting excipients and coated with polymeric blend of ethyl cellulose and hydroxypropyl methylethylcellulose E5 (4:1). The prepared tablets were characterized for various quality control tests and in vitro drug release. Evaluation of drug release kinetics through model fitting suggested the Fickian mechanism of drug release, which was regulated by osmosis and diffusion as the predominant mechanism. Evaluation of mucoadhesion property using texture analyzer suggested good mucoadhesion potential of the developed osmotic systems. Solid state characterization using Fourier-transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction spectroscopy confirmed the absence of any physiochemical incompatibilities between drug and excipients. Scanning electron microscopy analysis showed the smooth surface appearance of the coated tablets with intact polymeric membrane without any fracture. In vivo pharmacokinetic studies in rabbits revealed 3.01-fold enhancement in the oral bioavailability vis-à-vis the marketed formulation (Vastarel MR®). These studies successfully demonstrate the bioavailability enhancement potential of the mucoadhesive elementary osmotic pumps as novel therapeutic systems for other drugs too.

  19. Development of starch based mucoadhesive vaginal drug delivery systems for application in veterinary medicine.

    PubMed

    Gök, Mehmet Koray; Özgümüş, Saadet; Demir, Kamber; Cirit, Ümüt; Pabuccuoğlu, Serhat; Cevher, Erdal; Özsoy, Yıldız; Bacınoğlu, Süleyman

    2016-01-20

    The aim of this study was to prepare and evaluate the mucoadhesive, biocompatible and biodegradable progesterone containing vaginal tablets based on modified starch copolymers for the estrus synchronization of ewes. Starch-graft-poly(acrylic acid) copolymers (S-g-PAA) were synthesized and characterized. The vaginal tablets were fabricated with S-g-PAA and their equilibrium swelling degree (Qe) and matrix erosion (ME%) were determined in lactate buffer solution. In vitro, mucoadhesive properties of the tablets were investigated by using ewe vaginal mucosa and in vivo residence time were also investigated. In vitro and in vivo progesterone release profiles from the tablets were compared with two commercial products. Tablet formulation containing wheat starch based grafted copolymer (WS-g-PAA)gc indicated promising results and might be convenient as an alternative product to the commercial products in veterinary medicine.

  20. Improved mucoadhesive properties of self-nanoemulsifying drug delivery systems (SNEDDS) by introducing acyl chitosan.

    PubMed

    Efiana, Nuri Ari; Mahmood, Arshad; Lam, Hung Thanh; Zupančič, Ožbej; Leonaviciute, Gintare; Bernkop-Schnürch, Andreas

    2017-03-15

    This study was aimed to improve the mucoadhesive properties of SNEDDS by the incorporation of acyl chitosan including octanoyl chitosan (OC), lauroyl chitosan (LC) and palmitoyl chitosan (PC). SNEDDS and acyl chitosan SNEDDS were characterized regarding droplet size and zeta potential. Their mucoadhesivity on porcine intestinal mucosa was evaluated by falling liquid film technique using Sudan Red G as marker. Degree of substitution of chitosan was determined to be 52.8%, 64.8 and 48.5% for OC, LC and PC, respectively. SNEDDS and acyl chitosan SNEDDS displayed a droplet size less than 50nm and 80-300nm as well as a zeta potential of -0.2 to -1.6 and 0.05 to 0.99mV, respectively. Introducing 2% acyl chitosan into SNEDDS increased the residence time of SNEDDS on intestinal mucosa 2-fold. It is concluded that due to the incorporation of acyl chitosan into SNEDDS, their mucoadhesive properties can be increased. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. [The mucoadhesion phenomena and importance in drug application].

    PubMed

    Płaczek, Marcin; Sznitowska, Małgorzata

    2009-01-01

    The main assignment of the pharmaceutical sciences is to develop new, safer and more effective methods of pharmacotherapy. Among tools used to realize this goal are modern drug formulations, both for new and well known active substances. Different concepts have been proposed to achieve efficient drug delivery, and mucoadhesion has received a significant degree of attention during past years. Mucoadhesive systems, thanks to the presence of certain polymers, may attach for few hours to the mucosal membrane and therefore it is possible to obtain prolonged, local or systemic drug effect. This article contains an overview of data concerning the mucoadhesion phenomena and most important adhesion theories. Furthermore, methods that are frequently used to study the adhesion forces between drug and mucus as well as application of mucoadhesive hydrogels as drug carriers for different mucosal membranes are also discussed.

  2. Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties: preparation, characterization and application in a vaginal drug delivery system.

    PubMed

    Ci, Liqian; Huang, Zhigang; Liu, Yu; Liu, Zhepeng; Wei, Gang; Lu, Weiyue

    2017-09-01

    Lack of mucoadhesive properties is the major drawback to poloxamer 407 (F127)-based in situ hydrogels for mucosal administration. The objective of the present study was to construct a novel mucoadhesive and thermosensitive in situ hydrogel drug delivery system based on an amino-functionalized poloxamer for vaginal administration. First, amino-functionalized poloxamer 407 (F127-NH2) was synthesized and characterized with respect to its micellization behavior and interaction with mucin. Then using acetate gossypol (AG) as model drug, AG-loaded F127-NH2-based in situ hydrogels (NFGs) were evaluated with respect to rheology, drug release, ex vivo vaginal mucosal adhesion, in vivo intravaginal retention and local irritation after vaginal administration to healthy female mice. The results show that F127-NH2 is capable of forming a thermosensitive in situ hydrogel with sustained drug release properties. An interaction between positively charged F127-NH2 and negatively charged mucin was revealed by changes in the particle size and zeta potential of mucin particles as well as an increase in the complex modulus of NFG caused by mucin. Ex vivo and in vivo fluorescence imaging and quantitative analysis of the amount of AG remaining in mouse vaginal lavage all demonstrated greater intravaginal retention of NFG than that of an unmodified F127-based in situ hydrogel. In conclusion, amino group functionalization confers valuable mucoadhesive properties on poloxamer 407.

  3. Multistage pH-responsive mucoadhesive nanocarriers prepared by aerosol flow reactor technology: A controlled dual protein-drug delivery system.

    PubMed

    Shrestha, Neha; Shahbazi, Mohammad-Ali; Araújo, Francisca; Mäkilä, Ermei; Raula, Janne; Kauppinen, Esko I; Salonen, Jarno; Sarmento, Bruno; Hirvonen, Jouni; Santos, Hélder A

    2015-11-01

    Nanotechnology based drug delivery systems are anticipated to overcome the persistent challenges in oral protein and peptide administration, and lead to the development of long awaited non-invasive therapies. Herein, an advanced single-step aerosol flow reactor based technology was used to develop a multifunctional site specific dual protein-drug delivery nanosystem. For this purpose, mucoadhesive porous silicon (PSi) nanoparticles encapsulated into a pH-responsive polymeric nanomatrix was developed for advanced oral type 2 diabetes mellitus therapy with an antidiabetic peptide, glucagon like peptide-1 (GLP-1), and the enzyme inhibitor, dipeptidyl peptidase-4 (DPP4). Chitosan surface modification inherited the mucoadhesiveness to the nanosystem which led to enhanced cellular interactions and increased cellular compatibility. An advanced aerosol flow reactor technology was used to encapsulate the chitosan modified nanoparticles into an enteric polymeric nanomatrix. The pH-sensitive polymeric matrix simultaneously prevented the gastric degradation of the encapsulated peptide and also preserved the mucoadhesive functionality of the chitosan-modified PSi nanoparticles in the harsh stomach environment. The multidrug loaded nanosystem showed augmented intestinal permeability of GLP-1, evaluated in an in vitro cell-based intestinal epithelium model, attributed to the permeation enhancer effect of chitosan and inhibition of GLP-1 degradation by the DPP4 inhibitor. The applied technology resulted in the development of a dual-drug delivery nanosystem that synergizes the antidiabetic effect of the loaded peptide and the enzyme inhibitor, thereby indicating high clinical potential of the system and preparation technique. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Mucoadhesive platforms for targeted delivery to the colon.

    PubMed

    Varum, Felipe J O; Veiga, Francisco; Sousa, João S; Basit, Abdul W

    2011-11-25

    A novel platform system, comprising a mucoadhesive core and a rapid release carrier, was designed for targeted drug delivery to the colon. Prednisolone pellets containing different carbomers, including Carbopol 971P, Carbopol 974P and Polycarbophil AA-1, with or without organic acids, were produced by extrusion-spheronization. Mucoadhesive pellets were coated with a new enteric double-coating system, which dissolves at pH 7. This system comprises an inner layer of partially neutralized Eudragit S and buffer salt and an outer coating of standard Eudragit S. A single layer of standard Eudragit S was also applied for comparison purposes. Dissolution of the coated pellets was assessed in USP II apparatus in 0.1N HCl followed by Krebs bicarbonate buffer pH 7.4. Visualization of the coating dissolution process was performed by confocal laser scanning microscopy using fluorescent markers in both layers. The mucoadhesive properties of uncoated, single-coated and-double coated pellets were evaluated ex vivo on porcine colonic mucosa. Mucoadhesive pellets coated with a single layer of Eudragit S release its cargo after a lag time of 120 min in Krebs buffer. In contrast, drug release from the double-coated mucoadhesive pellets was significantly accelerated, starting at 75 min. In addition, the mucoadhesive properties of the core of the double coated pellets were higher than those from single-coated pellets after the core had been exposed to the buffer medium. This novel platform technology has the potential to target the colon and overcome the variability in transit and harmonize drug release and bioavailability.

  5. Evaluation of poly(acrylic acid-co-ethylhexyl acrylate) films for mucoadhesive transbuccal drug delivery: factors affecting the force of mucoadhesion.

    PubMed

    Shojaei, A H; Paulson, J; Honary, S

    2000-07-03

    Based on the premise that similar surface properties between the adhesive and the substrate would yield a strong adhesive bond, copolymers of acrylic acid (AA) and 2-ethylhexyl acrylate (EHA), P(AA-co-EHA), were designed and synthesized for buccal mucoadhesion. A series of linear copolymers with varying feed ratios of the two monomers (AA and EHA) were synthesized through free radical copolymerization at 69+/-0.5 degrees C using azobis(isobutyronitrile) (AIBN) as initiator. The reactions were carried out in THF under nitrogen for 24 h. The glass transition temperatures, T(g), of the copolymers were determined using DSC. The adhesion studies were conducted to determine the effects of copolymer composition, contact time between the substrate and the adhesive, and crosshead speed on mucoadhesive performance of the copolymer films using a computer interfaced Instron material testing system. The glass transition temperature of the copolymers decreased with increasing EHA content. Wet glass surface as substrate was shown not to be a good substrate model for adhesion determination studies. The copolymer composed of 46:54 mol.% AA:EHA (an almost 1:1 ratio in the repeat units) yielded the highest mucoadhesive force in contact with porcine buccal mucosa which was significantly greater (P<0.05) than that of poly(acrylic acid) (PAA) (used as positive control). The mucoadhesive force for all copolymers studied was significantly (P<0.05) greater than that of the negative control (backing material without copolymer film) except for the EHA homopolymer. Crosshead speed increased mucoadhesive force linearly and had a more pronounced effect on the mucoadhesive performance than time of contact between the adhesive and the substrate.

  6. Development and characterization of mucoadhesive patches of salbutamol sulfate for unidirectional buccal drug delivery.

    PubMed

    Puratchikody, Ayrivan; Prasanth, Viswanadhan Vasantha; Mathew, Sam Thomas; Kumar, Balaraman Ashok

    2011-06-01

    Buccal patches of salbutamol sulfate were prepared using five different water soluble polymers in various proportions and combinations using PEG-400/PG as plasticizers. A 32 full factorial design was used to design the experiments for each polymer combination. Patches were laminated on one side with a water impermeable backing layer for unidirectional drug release. The thickness of medicated patches ranged between 0.2 and 0.4 mm and showed an increase in mass whenever PEG-400 was used as plasticizer. The surface pH of all patches approached neutral. Eight formulations which had shown high folding endurance (> 300) were selected for evaluation. Patches prepared with PEG-400 showed a high swelling index. The residence time of the tested patches ranged between 105 and 130 min. Formulations A10, A32, B10 and B32 fitted the Higuchi model best, whereas formulations A19 and B19 showed super case II transport drug release. Stability studies indicated that there was no change in the chemical and physical characteristics during the test period of 6 months.

  7. Delivery of Exenatide and Insulin Using Mucoadhesive Intestinal Devices.

    PubMed

    Gupta, Vivek; Hwang, Byeong-Hee; Doshi, Nishit; Banerjee, Amrita; Anselmo, Aaron C; Mitragotri, Samir

    2016-06-01

    A major disadvantage associated with current diabetes therapy is dependence on injectables for long-term disease management. In addition to insulin, incretin hormone replacement therapies including exenatide have added a new class of drugs for Type-2 diabetes. Although efficacious, patient compliance with current diabetic therapy is poor due to requirement of injections, inability to cross the intestinal epithelium and instability in the gastrointestinal tract. Here, we report the efficacy of a mucoadhesive device in providing therapeutic concentrations of insulin and exenatide via oral administration. Devices were prepared with a blend of FDA-approved polymers, carbopol, pectin and sodium carboxymethylcellulose, and were tested for drug carrying capability, in vitro release, Caco-2 permeability, and in vivo efficacy for insulin and exenatide. Results suggested that mucoadhesive devices successfully provided controlled release of FITC-insulin, released significant amounts of drug, while providing noteworthy enhancement of drug transport across Caco-2 monolayers without compromising monolayer integrity. In-vivo administration of the devices provided significant enhancement of drug absorption with 13- and 80-fold enhancement of relative bioavailability for insulin and exenatide compared to intestinal injections with significant increase in half-lives, thus resulting in prolonged blood glucose reduction. This study validates the efficacy of mucoadhesive devices in promoting oral peptide delivery to improve patient compliance and dose adherence.

  8. Formulation and Optimization of Mucoadhesive Nanodrug Delivery System of Acyclovir

    PubMed Central

    Bhosale, UV; Kusum, Devi V; Jain, N

    2011-01-01

    Acyclovir is an antiviral drug used for the treatment of herpes simplex virus infections, with an oral bioavailability of only 10–20% [limiting absorption in gastrointestinal tract to duodenum and jejunum] and half-life of about 3 h, and is soluble only at acidic pH (pKa 2.27). Mucoadhesive polymeric nanodrug delivery systems of acyclovir have been designed and optimized using 23 full factorial design. Poly (lactic-co-glycolic acid) (PLGA) (50:50) was used as the polymer along with polycarbophil (Noveon AA-1) as the mucoadhesive polymer and pluronic F68 as the stabilizer. From the preliminary trials, the constraints for independent variables X1 (amount of PLGA), X2 (amount of pluronic F68) and X3 (amount of polycarbophil) have been fixed. The dependent variables that were selected for study were particle size (Y1), % drug entrapment (Y2) and % drug release in 12 h (Y3). The derived polynomial equations were verified by check point formulation. The application of factorial design gave a statistically systematic approach for the formulation and optimization of nanoparticles with the desired particle size, % drug release and high entrapment efficiency. Drug: Polymer ratio and concentration of stabilizer were found to influence the particle size and entrapment efficiency of acyclovir-loaded PLGA nanoparticles. The release was found to follow Fickian as well as non-Fickian diffusion mechanism with zero-order drug release for all batches. In vitro intestinal mucoadhesion of nanoparticles increased with increasing concentration of polycarbophil. These preliminary results indicate that acyclovir-loaded mucoadhesive PLGA nanoparticles could be effective in sustaining drug release for a prolonged period. PMID:22224033

  9. Transbuccal delivery of chlorpheniramine maleate from mucoadhesive buccal patches.

    PubMed

    Sekhar, K Chandra; Naidu, K V S; Vishnu, Y Vamshi; Gannu, Ramesh; Kishan, V; Rao, Y Madhusudan

    2008-01-01

    This article describes buccal permeation of chlorpheniramine maleate (CPM) and its transbuccal delivery using mucoadhesive buccal patches. Permeation of CPM was calculated in vitro using porcine buccal membrane and in vivo in healthy humans. Buccal formulations were developed with hydroxyethylcellulose (HEC) and evaluated for in vitro release, moisture absorption, mechanical properties, and bioadhesion, and optimized formulation was subjected for bioavailability studies in healthy human volunteers. In vitro flux of CPM was calculated to be 0.14 +/- 0.03 mg.h(-1).cm(-2) and buccal absorption also was demonstrated in vivo in human volunteers. In vitro drug release and moisture absorbed were governed by HEC content and formulations exhibited good tensile and mucoadhesive properties. Bioavailability from optimized buccal patch was 1.46 times higher than the oral dosage form and the results showed statistically significant difference.

  10. Characterization of different carbon nanotubes for the development of a mucoadhesive drug delivery system for intravesical treatment of bladder cancer.

    PubMed

    Rieger, Christiane; Kunhardt, David; Kaufmann, Anika; Schendel, Darja; Huebner, Doreen; Erdmann, Kati; Propping, Stefan; Wirth, Manfred P; Schwenzer, Bernd; Fuessel, Susanne; Hampel, Silke

    2015-02-20

    In order to increase the effectiveness of therapeutics for bladder carcinoma (BCa) treatment, alternative strategies for intravesical applications are needed. The use of carbon nanotubes (CNTs) as basis for a multifunctional drug transporter is a promising possibility to combine traditional chemotherapeutics with innovative therapeutic agents such as antisense oligodeoxynucleotides or small interfering RNA. In the current study four CNT types varying in length and diameter (CNT-1, CNT-2, CNT-3, CNT-4) were synthesized and then characterized with different spectroscopic techniques. Compared to the pristine CNT-1 and CNT-3, the shortened CNT-2 and CNT-4 exhibited more defects and lower aspect ratios. To analyze their mucoadhesive properties, CNTs were exposed to mouse bladders ex vivo by using Franz diffusion cells. All four tested CNT types were able to adhere to the urothelium with a mean covering area of 5-10%. In vitro studies on UM-UC-3 and EJ28 BCa cells were conducted to evaluate the toxic potential of these CNTs. Viability and cytotoxicity assays revealed that the shortened CNT-2 and CNT-4 induced stronger inhibitory effects on BCa cells than CNT-1 and CNT-3. In conclusion, CNT-1 and CNT-3 showed the most promising properties for further optimization of a multifunctional drug transporter.

  11. Brain targeting efficiency of antimigrain drug loaded mucoadhesive intranasal nanoemulsion.

    PubMed

    Abdou, Ebtsam M; Kandil, Soha M; Miniawy, Hala M F El

    2017-08-30

    Zolmitriptan (ZT) is a well-tolerated drug in migraine treatment suffering from low bioavailability due to low amount of the drug that reaches the brain after oral and nasal delivery. Development of new nasal mucoadhesive nanoemulsion formulation for zolmitriptan may success in delivering the drug directly from the nose to the brain to achieve rapid onset of action and high drug concentration in the brain which is required for treatment of acute migraine. ZT mucoadhesive nanoemulsion were prepared and characterized for drug content, zeta potential, particle size, morphology, residence time and permeation through the nasal mucosa. The selected formula was tested in-vivo in mice for its pharmacokinetics in comparison with intravenous and nasal solution of zolmitriptan. Results showed that addition of chitosan as mucoadhesive agent in 0.3% concentration to the nanoemulsion enhanced its residence time and zetapotential with no significant effect on the globule size. All tested formulations showed higher permeability coefficients than the zolmitriptan solution through the nasal mucosa. In-vivo studies showed that the mucoadhesive nanoemulsion formulation of zolmitriptan has higher AUC0-8 and shorter Tmax in the brain than the intravenous or the nasal solution. This was related to the small globule size and higher permeability of the formulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement.

    PubMed

    Li, ChunYan; Huang, ZhiGang; Liu, ZheShuo; Ci, LiQian; Liu, ZhePeng; Liu, Yu; Yan, XueYing; Lu, WeiYue

    Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs) demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutics interferon (IFN) in vitro, but their poor stability and obvious tendency to aggregate over time severely limited future application. In this study, sulfonate-modified PBNPs (PBNP-S) were designed as a stable mucoadhesive drug delivery system where the negative charges conferred by sulfonate groups prevented aggregation of nanoparticles and the phenylboronic acid groups ensured effective interaction with mucin over a wide pH range. Results suggested that PBNP-S were of spherical morphology with narrow size distribution (123.5 nm, polydispersity index 0.050), good stability over a wide pH range and 3-month storage and considerable in vitro mucoadhesion capability at vaginal pH as shown by mucin adsorption determination. IFN could be loaded to PBNP-S by physical adsorption with high encapsulation efficiency and released in a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent assay (ELISA) assay of IFN demonstrated that PBNP-S could stay in the vagina and maintain intravaginal IFN level for much longer time than IFN solution (24 hours vs several hours) without obvious histological irritation to vaginal mucosa after vaginal administration to mice. In summary, good stability, easy loading and controllable release of protein therapeutics, in vitro and in vivo mucoadhesive properties and local safety of PBNP-S suggested it as a promising nanoscale mucoadhesive drug delivery

  13. Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement

    PubMed Central

    Li, ChunYan; Huang, ZhiGang; Liu, ZheShuo; Ci, LiQian; Liu, ZhePeng; Liu, Yu; Yan, XueYing; Lu, WeiYue

    2016-01-01

    Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs) demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutics interferon (IFN) in vitro, but their poor stability and obvious tendency to aggregate over time severely limited future application. In this study, sulfonate-modified PBNPs (PBNP-S) were designed as a stable mucoadhesive drug delivery system where the negative charges conferred by sulfonate groups prevented aggregation of nanoparticles and the phenylboronic acid groups ensured effective interaction with mucin over a wide pH range. Results suggested that PBNP-S were of spherical morphology with narrow size distribution (123.5 nm, polydispersity index 0.050), good stability over a wide pH range and 3-month storage and considerable in vitro mucoadhesion capability at vaginal pH as shown by mucin adsorption determination. IFN could be loaded to PBNP-S by physical adsorption with high encapsulation efficiency and released in a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent assay (ELISA) assay of IFN demonstrated that PBNP-S could stay in the vagina and maintain intravaginal IFN level for much longer time than IFN solution (24 hours vs several hours) without obvious histological irritation to vaginal mucosa after vaginal administration to mice. In summary, good stability, easy loading and controllable release of protein therapeutics, in vitro and in vivo mucoadhesive properties and local safety of PBNP-S suggested it as a promising nanoscale mucoadhesive drug delivery

  14. Role of mucoadhesive polymers in enhancing delivery of nimodipine microemulsion to brain via intranasal route.

    PubMed

    Pathak, Rudree; Prasad Dash, Ranjeet; Misra, Manju; Nivsarkar, Manish

    2014-04-01

    Intranasal drug administration is receiving increased attention as a delivery method for bypassing the blood-brain barrier and rapidly targeting therapeutics to the CNS. However, rapid mucociliary clearance in the nasal cavity is a major hurdle. The purpose of this study was to evaluate the effect of mucoadhesive polymers in enhancing the delivery of nimodipine microemulsion to the brain via the intranasal route. The optimized mucoadhesive microemulsion was characterized, and the in vitro drug release and in vivo nasal absorption of drug from the new formulation were evaluated in rats. The optimized formulation consisted of Capmul MCM as oil, Labrasol as surfactant, and Transcutol P as co-surfactant, with a particle size of 250 nm and zeta potential value of -15 mV. In vitro and ex vivo permeation studies showed an initial burst of drug release at 30 min and sustained release up to 6 h, attributable to the presence of free drug entrapped in the mucoadhesive layer. In vivo pharmacokinetic studies in rats showed that the use of the mucoadhesive microemulsion enhanced brain and plasma concentrations of nimodipine. These results suggest that incorporation of a mucoadhesive agent in a microemulsion intranasal delivery system can increase the retention time of the formulation and enhance brain delivery of drugs.

  15. Effect of Different Polymer Concentration on Drug Release Rate and Physicochemical Properties of Mucoadhesive Gastroretentive Tablets.

    PubMed

    Agarwal, Shweta; Murthy, R S R

    2015-01-01

    Mucoadhesive tablets have emerged as potential candidates for gastroretentive drug delivery providing controlled release along with prolonged gastric residence time. Gastroretentive mucoadhesive tablets could result in increased bioavailability due to prolonged gastric residence time. A hydrophilic matrix system was developed as mucoadhesion is achievable on appropriate wetting and swelling of the polymers used. The polymers were so chosen so as to provide a balance between swelling, mucoadhesion and drug release. The polymers chosen were hydroxypropyl methylcellulose K4M, chitosan, and Carbopol 934. The concentrations of these polymers used has a great impact on the physicochemical properties of the resulting formulation. The tablets were formulated using wet granulation method and tranexamic acid was used as the model drug. The prepared tablets were characterized for size, shape, appearance, hardness, friability, weight variation, swelling, mucoadhesion and in vitro drug release. Several batches of tablets were prepared by varying the ratio of hydroxypropyl methylcellulose K4M and Chitosan. The batches having a greater ratio of chitosan showed higher rate of swelling, greater erosion, less mucoadhesion and faster release rate of the drug whereas the batches having greater ratio of hydroxypropyl methylcellulose K4M showed lesser rate of swelling, less erosion, better mucoadhesion and a smaller drug release rate. The level of carbopol was kept constant in all the batches.

  16. Effect of Different Polymer Concentration on Drug Release Rate and Physicochemical Properties of Mucoadhesive Gastroretentive Tablets

    PubMed Central

    Agarwal, Shweta; Murthy, R. S. R.

    2015-01-01

    Mucoadhesive tablets have emerged as potential candidates for gastroretentive drug delivery providing controlled release along with prolonged gastric residence time. Gastroretentive mucoadhesive tablets could result in increased bioavailability due to prolonged gastric residence time. A hydrophilic matrix system was developed as mucoadhesion is achievable on appropriate wetting and swelling of the polymers used. The polymers were so chosen so as to provide a balance between swelling, mucoadhesion and drug release. The polymers chosen were hydroxypropyl methylcellulose K4M, chitosan, and Carbopol 934. The concentrations of these polymers used has a great impact on the physicochemical properties of the resulting formulation. The tablets were formulated using wet granulation method and tranexamic acid was used as the model drug. The prepared tablets were characterized for size, shape, appearance, hardness, friability, weight variation, swelling, mucoadhesion and in vitro drug release. Several batches of tablets were prepared by varying the ratio of hydroxypropyl methylcellulose K4M and Chitosan. The batches having a greater ratio of chitosan showed higher rate of swelling, greater erosion, less mucoadhesion and faster release rate of the drug whereas the batches having greater ratio of hydroxypropyl methylcellulose K4M showed lesser rate of swelling, less erosion, better mucoadhesion and a smaller drug release rate. The level of carbopol was kept constant in all the batches. PMID:26997698

  17. pH-dependent mucoadhesion of a poly(N-isopropylacrylamide) copolymer reveals design rules for drug delivery.

    PubMed

    Zhu, X; Degraaf, J; Winnik, F M; Leckband, D

    2004-11-23

    This study investigated the mucoadhesive property of a hydrophobically modified copolymer N-isopropylacryamide and glycidylacrylamide NIPAM-N-Gly-(C18)2 (NIPAM-Gly). Prior studies demonstrated that the interfacial properties of this copolymer are pH dependent and that the chains form strong hydrogen bonds at pH < 7 via the carboxylic acid side chains of the glycine moieties. Mucin interactions with the copolymer brushes were investigated by surface plasmon resonance and by direct force measurements. Mucin adsorption was determined as a function of pH, ionic strength, and mucin concentration. It adsorbs to the copolymer strongly at pH 5, but the adsorption decreases with increasing pH. The adsorbed amount is also ionic-strength dependent, decreasing with increasing monovalent salt concentrations at all pH values investigated. When compared with similar investigations with poly(ethylene oxide), these results provide insights into both the chemical characteristics and the solution conditions that determine the mucoadhesive properties of polymers.

  18. Vaginal Delivery of Benzydamine Hydrochloride through Liposomes Dispersed in Mucoadhesive Gels.

    PubMed

    Tuğcu-Demiröz, Fatmanur

    2017-07-01

    Liposomal vaginal drug delivery systems are important strategy in the treatment of both topical and systemic diseases. The aim of this study was to develop a vaginal delivery system for benzydamine hydrochloride (BNZ) loaded liposomes dispersed into mucoadhesive gels. The delivery system was also designed for a once a day dosage and to obtain controlled release of the BNZ. For this purpose BNZ containing gel formulations using hydroxypropyl methylcellulose (HPMC) K100M and Carbopol(®) 974P, which are composed of polymers that show promising potential as mucoadhesive vaginal delivery systems, were developed. In addition, a BNZ containing liposome formulation was developed for vaginal administration. To improve the vaginal retention time, liposome was incorporated in HPMC K100M and Carbopol(®) 974P gel formulations. This system is called lipogel. The developed BNZ liposomes have a slightly negative zeta potential (-1.50±0.16 mV), a 2.25±0.009 µm particle size and a 34% entrapment efficiency. These gels and lipogels have appropriate pH, viscosity, textural properties and mucoadhesive value for vaginal administration. Lipogels were found to be the best formulations for in vitro diffusion and ex vivo mucoadhesion. The work of mucoadhesion obtained from liposomes was in the range of 0.027±0.045 and 0.030±0.017 mJ/cm(2), while the value obtained from lipogels was between 0.176±0.037 and 0.243±0.53 mJ/cm(2). N1 and N2 lipogel formulations diffused 57 and 67% of BNZ respectively at the end of 24 h. Moreover, a higher mucoadhesion, which increases drug residence time in comparison to liposomes, could improve BNZ efficacy. In conclusion, BNZ mucoadhesive vaginal lipogel formulations can be promising alternatives to traditional dosage forms for vaginal topical therapy.

  19. Rheological, mechanical and mucoadhesive properties of thermoresponsive, bioadhesive binary mixtures composed of poloxamer 407 and carbopol 974P designed as platforms for implantable drug delivery systems for use in the oral cavity.

    PubMed

    Jones, David S; Bruschi, Marcos Luciano; de Freitas, Osvaldo; Gremião, Maria Palmira Daflon; Lara, Elza Helena Guimarães; Andrews, Gavin P

    2009-05-08

    This study described the formulation and characterisation of the viscoelastic, mechanical and mucoadhesive properties of thermoresponsive, binary polymeric systems composed of poloxamer (P407) and poly(acrylic acid, C974P) that were designed for use as a drug delivery platform within the oral cavity. Monopolymeric and binary polymeric formulations were prepared containing 10, 15 and 20% (w/w) poloxamer (407) and 0.10-0.25% (w/w) poly(acrylic acid, 934P). The flow rheological and viscoelastic properties of the formulations were determined using controlled stress and oscillatory rheometry, respectively, the latter as a function of temperature. The mechanical and mucoadhesive properties (namely the force required to break the bond between the formulation and a pre-hydrated mucin disc) were determined using compression and tensile analysis, respectively. Binary systems composed of 10% (w/w) P407 and C934P were elastoviscous, were easily deformed under stress and did not exhibit mucoadhesion. Formulations containing 15 or 20% (w/w) Pluronic P407 and C934P exhibited a sol-gel temperature T(sol/gel), were viscoelastic and offered high elasticity and resistance to deformation at 37 degrees C. Conversely these formulations were elastoviscous and easily deformed at temperatures below the sol-gel transition temperature. The sol-gel transition temperatures of systems containing 15% (w/w) P407 were unaffected by the presence of C934P; however, increasing the concentration of C934P decreased the T(sol/gel) in formulations containing 20% (w/w) P407. Rheological synergy between P407 and C934P at 37 degrees C was observed and was accredited to secondary interactions between these polymers, in addition to hydrophobic interactions between P407 micelles. Importantly, formulations composed of 20% (w/w) P407 and C934P exhibited pronounced mucoadhesive properties. The ease of administration (below the T(sol/gel)) in conjunction with the viscoelastic (notably high elasticity) and

  20. Thiolated graphene oxide as promising mucoadhesive carrier for hydrophobic drugs.

    PubMed

    Pereira de Sousa, Irene; Buttenhauser, Katrin; Suchaoin, Wongsakorn; Partenhauser, Alexandra; Perrone, Mara; Matuszczak, Barbara; Bernkop-Schnürch, Andreas

    2016-07-25

    The aim of this study was to improve the mucoadhesive properties of graphene by conjugating thiol ligands, in order to formulate an oral delivery system for hydrophobic drugs showing long mucus residence time. Graphene oxide was obtained by oxidation of graphite and then was thiolated following two synthetic paths. On the one hand, the hydroxyl groups were conjugated with thiourea passing through the formation of a brominated intermediate. On the other hand, the carboxylic acid groups were conjugated with cysteamine via carbodiimide chemistry. The mucoadhesive properties of thiolated graphene were evaluated by rheological measurements and by residence time assay. Then, valsartan was loaded on thiolated graphene and the release profile was evaluated in simulated intestinal fluid. Following both synthetic paths it was possible to obtain thiolated graphene bearing 215-302μmol SH/g product. Both products induced after 1h incubation an increase of mucus viscosity of about 22-33-fold compared to unmodified graphite. The residence time assay confirmed that 60% of thiolated graphene could be retained on intestinal mucosa after 4h incubation, whereas just 20% of unmodified graphite could be retained. Valsartan could be loaded with a drug loading of about 31±0.3% and a sustained release profile was observed for both formulations. According to the presented data, the thiolation of graphene could improve its mucoadhesive properties. Therefore, thiolated graphene represents a promising platform for oral delivery of hydrophobic drugs, possessing a long residence time on intestinal mucosa which allows the release of the loaded drug close to the adsorptive epithelium. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Advances in mucoadhesion and mucoadhesive polymers.

    PubMed

    Khutoryanskiy, Vitaliy V

    2011-06-14

    Mucoadhesion is the ability of materials to adhere to mucosal membranes in the human body and provide a temporary retention. This property has been widely used to develop polymeric dosage forms for buccal, oral, nasal, ocular and vaginal drug delivery. Excellent mucoadhesive properties are typical for hydrophilic polymers possessing charged groups and/or non-ionic functional groups capable of forming hydrogen bonds with mucosal surfaces. This feature article considers recent advances in the study of mucoadhesion and mucoadhesive polymers. It provides an overview on the structure of mucosal membranes, properties of mucus gels and the nature of mucoadhesion. It describes the most common methods to evaluate mucoadhesive properties of various dosage forms and discusses the main classes of mucoadhesives.

  2. Mucoadhesive Buccal Tablets Based on Chitosan/Gelatin Microparticles for Delivery of Propranolol Hydrochloride.

    PubMed

    Abruzzo, Angela; Cerchiara, Teresa; Bigucci, Federica; Gallucci, Maria Caterina; Luppi, Barbara

    2015-12-01

    Propranolol administration through buccal route offers some distinct advantages thanks to the easy access to the oral mucosa, fast onset of action, and avoidance of hepatic and intestinal degradation mechanisms. To overcome the effective removal existing in the buccal cavity, mucoadhesive delivery systems are considered a promising approach as they facilitate a close contact with the buccal mucosa. The aim of this study was to prepare mucoadhesive tablets based on chitosan/gelatin microparticles for buccal delivery of propranolol hydrochloride. Spray-dried microparticles were prepared with different chitosan-gelatin weight ratios and characterized in terms of yield and morphology. Microparticles were subsequently compressed with the drug to obtain loaded buccal tablets. In vitro water uptake, mucoadhesion, release, and permeation tests were performed to investigate tablet ability to hydrate, to adhere to the mucosa, and to deliver drug through buccal mucosa. Microparticles showed a different morphology based on the different chitosan-gelatin weight ratios. Moreover, buccal tablets based on the prepared microparticles showed different technological and functional characteristics in virtue of their composition. In particular, tablets with an excess of chitosan showed the best mucoadhesive properties, allowed the permeation of the greatest drug amount among all formulations, and could be promising for buccal administration of propranolol hydrochloride. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  3. Mucoadhesive liposomes as new formulation for vaginal delivery of curcumin.

    PubMed

    Berginc, Katja; Suljaković, Sabina; Škalko-Basnet, Nataša; Kristl, Albin

    2014-05-01

    Local delivery to the affected area represents the optimal means by which advantageous pharmacological properties of curcumin may be fully exploited as currently, due to the biopharmaceutical limitations associated with this polyphenol, its full beneficial effects remain limited. Curcumin-containing liposomes coated with bioadhesive polymers of natural and synthetic origin (chitosan and Carbopol) were evaluated in vitro. For these purposes, an in vitro model of vaginal mucus was developed allowing the monitoring of curcumin permeability in the conditions mimicking vaginal environment. The model was optimized by varying the amounts of glycoproteins, as compared to the permeabilities determined through isolated bovine mucus. The strength of bioadhesion was evaluated using the isolated bovine mucosa. Both curcumin solution and non-coated curcumin liposomes served as controls. Bioadhesive polymers enabled significantly higher (p<0.05) curcumin permeability through the artificial and isolated bovine mucus compared to the controls. Polymer coating of liposomes resulted in an increase in their bioadhesiveness. Mucoadhesive liposomes can be considered as potential novel drug delivery systems intended for vaginal administration of curcumin. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. The quest for targeted delivery in colon cancer: mucoadhesive valdecoxib microspheres

    PubMed Central

    Thakral, Naveen K; Ray, Alok R; Bar-Shalom, Daniel; Eriksson, André Huss; Majumdar, Dipak K

    2011-01-01

    The aim of the present study was to prepare valdecoxib, a cyclo-oxygenase-2 enzyme inhibitor, as a loaded multiparticulate system to achieve site-specific drug delivery to colorectal tumors. Film coating was done with the pH-sensitive polymer Eudragit S100 and sodium alginate was used as mucoadhesive polymer in the core. The microspheres were characterized by X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy and were evaluated for particle size, drug load, in vitro drug release, release kinetics, accelerated stability, and extent of mucoadhesion. The coated microspheres released the drug at pH 7.4, the putative parameter for colonic delivery. When applied to the mucosal surface of freshly excised goat colon, microspheres pretreated with phosphate buffer pH 7.4 for 30 minutes showed mucoadhesion. To ascertain the effect of valdecoxib on the viability of Caco-2 cells, the 3-(4,5-dimethylthiazol-2yl) 2,5-diphenyltetrazolium bromide) test was conducted using both valdecoxib and coated microspheres. In both cases, the percentage of dehydrogenase activity indicated a lack of toxicity against Caco-2 cells in the tested concentration range. Drug transport studies of the drug as well as the coated microspheres in buffers of pH 6 and 7.4 across Caco-2 cell monolayers were conducted. The microspheres were found to exhibit slower and delayed drug release and lower intracellular concentration of valdecoxib. PMID:21720517

  5. Mucoadhesive Microparticles for Gastroretentive Delivery: Preparation, Biodistribution and Targeting Evaluation

    PubMed Central

    Hou, Jing-Yi; Gao, Li-Na; Meng, Fan-Yun; Cui, Yuan-Lu

    2014-01-01

    The aim of this research was to prepare and characterize alginate-chitosan mucoadhesive microparticles containing puerarin. The microparticles were prepared by an emulsification-internal gelatin method using a combination of chitosan and Ca2+ as cationic components and alginate as anions. Surface morphology, particle size, drug loading, encapsulation efficiency and swelling ratio, in vitro drug released, in vitro evaluation of mucoadhesiveness and Fluorescence imaging of the gastrointestinal tract were determined. After optimization of the formulation, the encapsulation efficiency was dramatically increased from 70.3% to 99.2%, and a highly swelling ratio was achieved with a change in particle size from 50.3 ± 11.2 μm to 124.7 ± 25.6 μm. In ethanol induced gastric ulcers, administration of puerarin mucoadhesive microparticles at doses of 150 mg/kg, 300 mg/kg, 450 mg/kg and 600 mg/kg body weight prior to ethanol ingestion significantly protected the stomach ulceration. Consequently, significant changes were observed in inflammatory cytokines, such as prostaglandin E2 (PGE2), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and interleukin1β (IL-1β), in stomach tissues compared with the ethanol control group. In conclusion, core-shell type pH-sensitive mucoadhesive microparticles loaded with puerarin could enhance puerarin bioavailability and have the potential to alleviate ethanol-mediated gastric ulcers. PMID:25470180

  6. Mucoadhesive and enzymatic inhibitory nanoparticles for transnasal insulin delivery.

    PubMed

    Wang, Yanxia; Zhang, Xinge; Cheng, Cui; Li, Chaoxing

    2014-04-01

    To develop a novel nanocarrier with mucoadhesion and enzymatic inhibition for transnasal insulin delivery. METHODS & METHODS: The physicochemical characterization of the nanoparticles included size and morphology, as well as mucoadhesion and enzymatic inhibition. The in vitro release of insulin from the nanoparticles was evaluated in 3 mg/ml glucose medium. The cytocompatibility of the nanoparticles was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The interactions of the nanoparticles with Caco-2 cells and nasal epithelia, and the effect of the nanoparticles on transnasal insulin delivery were estimated. The nanoparticles were spherical in shape, with an average size of 100 nm, and presented strong enzymatic inhibitory activity and high mucin adsorption ability. The insulinloaded nanoparticles showed the rapid insulin release in 3 mg/ml glucose medium. The nanoparticles were noncytotoxic to Caco-2 cells. Furthermore, the insulin-loaded nanoparticles overcame mucosal barriers and significantly decreased plasma glucose levels.

  7. Transmucosal delivery of oxytocin to rabbits using a mucoadhesive buccal patch.

    PubMed

    Li, C; Bhatt, P P; Johnston, T P

    1997-08-01

    A biocompatible, mucoadhesive buccal patch was evaluated in rabbits for transmucosal delivery of peptides. Oxytocin (OT) was incorporated into custom coformulations of Carbopol 974P and silicone polymer and the resulting plasma OT concentration versus time profiles determined following patch application. For comparative purposes, the mean values determined for the elimination half-life (t1/2), volume of distribution (Vd), and the total body clearance (CL) following intravenous injection of OT were 2.9 +/- 0.2 min, 85.3 +/- 6.7 ml, and 20.4 +/- 2.03 ml/min, respectively. Following application of oxytocin-loaded mucoadhesive patches, plasma OT concentrations remained 20- to 28-fold greater from 0.5 to 3.0 hr than control animals administered placebo patches. The steady-state plasma OT concentration (Css) following application of the buccal patches was 80.6 +/- 15.9 pg/ml. The lag-time associated with attainment of the Css was 0.45 +/- 0.18 hr. Steady-state flux (Jss) of oxytocin in vivo was 139 +/- 36.8 ng/hr/cm2. Based on the amount of OT remaining in the patches following removal, the average dose of OT released in vivo was 0.27 +/- 0.024 mg with a bioavailability of 0.1%. No significant alterations in mucosal histology were observed when underlying mucosa to which OT patches had been applied were compared to either control (no patch) mucosa or mucosa underneath placebo patches. The mucoadhesive buccal patches were easy to apply and remove, nonirritating to tissue, and able to continuously deliver a nonapeptide over 3 hr. Based on these preliminary studies, the mucoadhesive buccal patches evaluated may represent an improved transmucosal drug delivery system for peptides and conventional drug substances.

  8. COMPETING PROPERTIES OF MUCOADHESIVE FILMS DESIGNED FOR LOCALIZED DELIVERY OF IMIQUIMOD

    PubMed Central

    Ramineni, Sandeep K; Cunningham, Larry L; Dziubla, Thomas D; Puleo, David A

    2013-01-01

    Oral mucosal delivery has gained prominence in the last two decades because the rich vasculature of the tissue enables rapid delivery and avoidance of first pass metabolism. Although commercial mucoadhesives are used for systemic delivery, systems are not currently available for treatment of local conditions. In the present work, mucoadhesive films are being developed for locally controlled release of an immune response modifier for preventing precancerous lesions from progressing to oral squamous cell carcinoma. Previous research showed that films composed of polyvinylpyrrolidone (PVP) and carboxymethylcellulose (CMC) released imiquimod in a sustained manner for 3 hr. In continuing development of the system, additional key properties were investigated with changes in composition. While adhesive properties in pull-off (0.42±0.03 to 1.1±0.1 N/cm2) and shear adhesion (1.7±0.25 to 5.6±1.4 N/cm2) increased with increasing PVP content of films, tensile properties, such as modulus (6.9±1.5 to 1.8±0.2 MPa) and ultimate strength (4.2±0.7 to 2.1±0.02 MPa), decreased as PVP content increased. Release profiles of the films showed that an increased PVP content resulted in burst release and faster erosion compared to sustained release and slower erosion with more CMC. Studies of transport kinetics showed that the films doubled the amount of imiquimod localized within epithelium compared to drug in solution, increasing their potential for local treatment of oral dysplasia. The mucoadhesive drug delivery system based on CMC and PVP offers a wide range of these properties without addition of new constituents. PMID:23750320

  9. Thermosensitive and mucoadhesive sol-gel composites of paclitaxel/dimethyl-β-cyclodextrin for buccal delivery.

    PubMed

    Choi, Soon Gil; Lee, Sang-Eun; Kang, Bong-Seok; Ng, Choon Lian; Davaa, Enkhzaya; Park, Jeong-Sook

    2014-01-01

    The purpose of this study was to develop a buccal paclitaxel delivery system using the thermosensitive polymer Pluronic F127 (PF127) and the mucoadhesive polymer polyethylene oxide (PEO). The anticancer agent paclitaxel is usually used to treat ovarian, breast, and non-small-cell lung cancer. To improve its aqueous solubility, paclitaxel was incorporated into an inclusion complex with (2,6-di-O-methyl)-β-cyclodextrin (DMβCD). The formation of the paclitaxel inclusion complex was evaluated using various techniques, including x-ray diffractometry (XRD), Fourier-transform infrared (FT-IR) spectrophotometry, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Hydrogels were prepared using a cold method. Concentrations of 18, 20, and 23% (w/v) PF127 were dissolved in distilled water including paclitaxel and stored overnight in a refrigerator at 4 °C. PEO was added at concentrations of 0.1, 0.2, 0.4, 0.8, and 1% (w/v). Each formulation included paclitaxel (0.5 mg/mL). The sol-gel transition temperature of the hydrogels was measured using the tube-inverting method. Drug release from the hydrogels was measured using a Franz diffusion cell containing pH 7.4 phosphate-buffered solution (PBS) buffer at 37 °C. The cytotoxicity of each formulation was measured using the MTT assay with a human oral cancer cell (KB cell). The sol-gel transition temperature of the hydrogel decreased when PF127 was present and varied according to the presence of mucoadhesive polymers. The in vitro release was sustained and the release rate was slowed by the addition of the mucoadhesive polymer. The cytotoxicity of the blank formulation was low, although the drug-loaded hydrogel showed acceptable cytotoxicity. The results of our study suggest that the combination of a PF 127-based mucoadhesive hydrogel formulation and inclusion complexes improves the in vitro release and cytotoxic effect of paclitaxel.

  10. Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics

    PubMed Central

    Gavin, Amy; Pham, Jimmy TH; Wang, Dawei; Brownlow, Bill; Elbayoumi, Tamer A

    2015-01-01

    Oral cavity and oropharyngeal cancers are considered the eighth most common cancer worldwide, with relatively poor prognosis (62% of patients surviving 5 years, after diagnosis). The aim of this study was to develop a proof-of-concept mucoadhesive lozenge/buccal tablet, as a potential platform for direct sustained delivery of therapeutic antimitotic nanomedicines. Our system would serve as an adjuvant therapy for oral cancer patients undergoing full-scale diagnostic and operative treatment plans. We utilized lipid-based nanocarriers, namely nanoemulsions (NEs), containing mixed-polyethoxylated emulsifiers and a tocopheryl moiety–enriched oil phase. Prototype NEs, loaded with the proapoptotic lipophilic drug genistein (Gen), were further processed into buccal tablet formulations. The chitosan polyelectrolyte solution overcoat rendered NE droplets cationic, by acting as a mucoadhesive interfacial NE layer. With approximate size of 110 nm, the positively charged chitosan-layered NE (+25 mV) vs negatively charged chitosan-free/primary aqueous NE (−28 mV) exhibited a controlled-release profile and effective mucoadhesion for liquid oral spray prototypes. When punch-pressed, porous NE-based buccal tablets were physically evaluated for hardness, friability, and swelling in addition to ex vivo tissue mucoadhesion force and retention time measurements. Chitosan-containing NE tablets were found equivalent to primary NE and placebo tablets in compression tests, yet significantly superior in all ex vivo adhesion and in vitro release assays (P≤0.05). Following biocompatibility screening of prototype chitosan-layered NEs, substantial anticancer activity of selected cationic Gen-loaded NE formulations, against two oropahryngeal carcinomas, was observed. The data strongly indicate the potential of such nanomucoadhesive systems as maintenance therapy for oral cancer patients awaiting surgical removal, or postresection of identified cancerous lesions. PMID:25759580

  11. Bilayer mucoadhesive microparticles for the delivery of metoprolol succinate: Formulation and evaluation.

    PubMed

    Kumar, Krishan; Dhawan, Neha; Sharma, Harshita; Patwal, Pramod S; Vaidya, Shubha; Vaidya, Bhuvaneshwar

    2015-01-01

    Metoprolol succinate is a very potent drug for the treatment of hypertension but suffers from poor bioavailability due to its erratic absorption in lower GI tract. Therefore, in the present study, it was hypothesized that by formulating mucoadhesive particles, the residence time in the GIT and release of drug may be prolonged that will enhance the bioavailability of metoprolol succinate. Metoprolol succinate loaded chitosan microparticles were prepared by ionic gelation method. The optimized microparticles were coated with sodium alginate to form a layer over chitosan microparticles to increase the mucoadhesive strength and to release the drug in controlled manner. Coated and uncoated microparticles were evaluated for particle size, zeta potential, morphology, entrapment efficiency, drug loading and in vitro drug release. The coated microparticles showed comparatively less drug release in the 0.1 N HCl while sustained release in PBS (pH 6.8) as compared to uncoated microparticles. The in vivo study on albino rats demonstrated an increase in bioavailability of the coated microparticles as compared to marketed formulation. From the study it can be concluded that alginate coated chitosan microparticles could be a useful carrier for the oral delivery of metoprolol succinate.

  12. Bioactivation antioxidant and transglycating properties of N-acetylcarnosine autoinduction prodrug of a dipeptide L-carnosine in mucoadhesive drug delivery eye-drop formulation: powerful eye health application technique and therapeutic platform.

    PubMed

    Babizhayev, Mark A

    2012-06-01

    A considerable interest in N-acetylcarnosine ocular drug design for eye health is based on clinical strategies to improve ocular drug delivery through metabolic enzymatic activation. Human biology aspects of ocular N-acetylcarnosine deacetylation during its pass through the cornea to the aqueous humor and dipeptide hydrolyzing enzymes are characterized. Novel approaches to ocular drug delivery increasing intraocular bioavailability of N-acetylcarnosine biologically activated metabolite carnosine become an integral development ensuring prolonged retention of the medication in the mucoadhesive precorneal area and facilitating transcorneal penetration of the natural dipeptide with the corneal promoters. A comprehensive list of techniques for peptide drug design, synthesis, purification, and biological analyses was considered: liquid chromatography (LC), high performance liquid chromatography (HPLC), (1) H and (13) C nuclear magnetic resonance (NMR), electrospray ionization (ESI) mass spectroscopy, and spectrophotometry. The antioxidant activity of therapeutics-targeted molecules was studied in aqueous solution and in a lipid membrane environment. A deglycation therapeutic system was developed involving removal, by transglycation of sugar or aldehyde moieties from Schiff bases by histidyl-hydrazide compounds or aldehyde scavenger L-carnosine. Clinical studies included ophthalmoscopy, visual acuity (VA), halometer disability glare tests, slit-image, and retro-illumination photography. N-acetylcarnosine 1% lubricant eye drops are considered as an auto-induction prodrug and natural ocular redox state balance therapies with implications in prevention and treatment of serious eye diseases that involve pathways of continuous oxidative damage to ocular tissues(cataracts, primary open-angle glaucoma, age-related macular degeneration) and sight-threatening glycosylation processes (diabetic retinopathy and consequent visual impairment) important for public health. The results of

  13. Gastroretentive delivery of rifampicin: in vitro mucoadhesion and in vivo gamma scintigraphy.

    PubMed

    Pund, Swati; Joshi, Amita; Vasu, Kamala; Nivsarkar, Manish; Shishoo, Chamanlal

    2011-06-15

    Rifampicin, a first line anti-tubercular drug, has maximum solubility and permeability in the stomach. An oral multi-particulate formulation with site specific sustained delivery of rifampicin was developed. This oral gastroretentive rifampicin formulation consisted of rifampicin pellets for immediate release as the loading dose and a bio/mucoadhesive rifampicin tablet for extended release. Immediate release pellets of rifampicin were prepared by extrusion-spheronization process and were evaluated for physico-mechanical properties: usable yield, size, shape, abrasion resistance, mechanical crushing force, residual moisture and drug release. For the mucoadhesive rifampicin formulation, statistical experimental strategy was utilized to simultaneously optimize the effect of two independent variables namely amount of Carbopol and MCC. The two dependent responses selected were, work of adhesion; estimated using Texture Analyzer and T(50%); determined from dissolution studies. Graphical and mathematical analysis of the results allowed the identification and quantification of the formulation variables influencing the selected responses. To study the gastrointestinal transit of the optimized gastroretentive formulation, the in vivo gamma scintigraphy was carried out in six healthy human volunteers, after radiolabeling the formulation with (99m)Tc. The transit profiles demonstrated that the dosage form was retained in the stomach for more than 320 min. The human data validates the design concept and signifies the potential of the developed system for stomach targeted delivery of rifampicin for improved bioavailability.

  14. Mucoadhesive multiparticulate patch for the intrabuccal controlled delivery of lidocaine.

    PubMed

    Cavallari, Cristina; Fini, Adamo; Ospitali, Francesca

    2013-04-01

    The aim of the present study was to prepare and evaluate patches for the controlled release of lidocaine in the oral cavity. Mucoadhesive buccal patches, containing 8 mg/cm(2) lidocaine base, were formulated and developed by solvent casting method technique, using a number of different bio-adhesive and film-forming semi-synthetic and synthetic polymers (Carbopol, Poloxamer, different type Methocel) and plasticizers (PEG 400, triethyl citrate); the patches were evaluated for bioadhesion, in vitro drug release and permeation using a modified Franz diffusion cell. A lidocaine/Compritol solid dispersion in the form of microspheres, embedded inside the patch, alone or together with free lidocaine, was also examined to prolong the drug release. The effects of the composition were evaluated considering a number of technological parameters and the release of the drug. All the formulations tested offer a variety of drug release mechanisms, obtaining a quick or delayed or prolonged anesthetic local activity with simple changes of the formulation parameters. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Mucoadhesive microspheres for nasal administration of an antiemetic drug, metoclopramide: in-vitro/ex-vivo studies.

    PubMed

    Gavini, Elisabetta; Rassu, Giovanna; Sanna, Vanna; Cossu, Massimo; Giunchedi, Paolo

    2005-03-01

    Microparticulate delivery systems designed for the nasal administration of an antiemetic drug, metoclopramide hydrochloride, were prepared. Microspheres composed of sodium alginate, chitosan hydrochloride, or both, were obtained using a spray-drying method; some batches of drug-free microparticles were prepared as a comparison. The morphology, in-vitro swelling behaviour, mucoadhesive properties and drug release from microparticles were evaluated. Ex-vivo drug permeation tests were carried out using sheep nasal mucosa; permeation test of the drug solution was performed as comparison. During ex-vivo permeation tests, transmission electron microscopy (TEM) analyses were carried out on the nasal mucosa to study the morphological changes of epithelial cells and tight junctions, while the change in microsphere morphology was examined using photostereo microscopy (PM). Spray-dried microparticles had a mean diameter (d(vs)) in the range of about 3-10 microm. They showed good in-vitro mucoadhesive properties. In-vitro release profiles and swelling behaviour depended on their composition: the drug release occurred in 1-3 h. Ex-vivo studies showed that drug permeation through the mucosa from microparticles based on chitosan was higher than from those consisting of alginate alone. This can be related to the penetration enhancing properties of chitosan. Complexation of chitosan with alginate led to a control of the drug release. Microscopy observation of microspheres during the permeation tests revealed that microparticles swelled and gelled, maintaining their shape. TEM analyses of the mucosa after exposure to the microparticles consisting of alginate/chitosan showed opened tight junctions. This preliminary study shows that alginate/chitosan spray-dried microspheres have promising properties for use as mucoadhesive nasal carriers of an antiemetic drug.

  16. Thermosensitive and Mucoadhesive Sol-Gel Composites of Paclitaxel/Dimethyl-β-Cyclodextrin for Buccal Delivery

    PubMed Central

    Kang, Bong-Seok; Ng, Choon Lian; Davaa, Enkhzaya; Park, Jeong-Sook

    2014-01-01

    The purpose of this study was to develop a buccal paclitaxel delivery system using the thermosensitive polymer Pluronic F127 (PF127) and the mucoadhesive polymer polyethylene oxide (PEO). The anticancer agent paclitaxel is usually used to treat ovarian, breast, and non-small-cell lung cancer. To improve its aqueous solubility, paclitaxel was incorporated into an inclusion complex with (2,6-di-O-methyl)-β-cyclodextrin (DMβCD). The formation of the paclitaxel inclusion complex was evaluated using various techniques, including x-ray diffractometry (XRD), Fourier-transform infrared (FT-IR) spectrophotometry, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Hydrogels were prepared using a cold method. Concentrations of 18, 20, and 23% (w/v) PF127 were dissolved in distilled water including paclitaxel and stored overnight in a refrigerator at 4°C. PEO was added at concentrations of 0.1, 0.2, 0.4, 0.8, and 1% (w/v). Each formulation included paclitaxel (0.5 mg/mL). The sol-gel transition temperature of the hydrogels was measured using the tube-inverting method. Drug release from the hydrogels was measured using a Franz diffusion cell containing pH 7.4 phosphate-buffered solution (PBS) buffer at 37°C. The cytotoxicity of each formulation was measured using the MTT assay with a human oral cancer cell (KB cell). The sol-gel transition temperature of the hydrogel decreased when PF127 was present and varied according to the presence of mucoadhesive polymers. The in vitro release was sustained and the release rate was slowed by the addition of the mucoadhesive polymer. The cytotoxicity of the blank formulation was low, although the drug-loaded hydrogel showed acceptable cytotoxicity. The results of our study suggest that the combination of a PF 127-based mucoadhesive hydrogel formulation and inclusion complexes improves the in vitro release and cytotoxic effect of paclitaxel. PMID:25275485

  17. Changes in the mucoadhesion of powder formulations after drug application investigated with a simplified method.

    PubMed

    Fransén, Nelly; Björk, Erik; Edsman, Katarina

    2008-09-01

    The residence time in the nasal cavity can be prolonged by dry particles that absorb water and subsequently increase the viscosity of the mucus layer. A novel nasal drug delivery system based on interactive mixtures has previously been developed, where fine particles of the active component are adhered to the surface of mucoadhesive carrier particles by dry mixing. The surface coverage may alter the original mucoadhesiveness of the carrier particles and to investigate this, a simplified tensile strength method was developed and evaluated. Reliable results were obtained with a plastic coated absorbent paper covered by a mucin solution as a substitution for porcine nasal mucosa and should also be applicable to other dry particle systems. The method showed that the swelling of sodium starch glycolate particles was slightly delayed, corresponding to the degree of hydrophobic surface coverage. Carrier particles of partly pregelatinized maize starch were not influenced by the addition of a hydrophobic substance, probably because of the rough particle shape that inhibited a complete surface coverage. It was concluded that the surface coverage of carrier particles in interactive mixtures only could cause a short delay in water absorption that should not affect their mucoadhesive characteristics in vivo.

  18. Sinonasal Delivery of Resveratrol via Mucoadhesive Nanostructured Microparticles in a Nasal Polyp Mouse Model

    PubMed Central

    Lee, Mingyu; Park, Chun Gwon; Huh, Beom Kang; Kim, Se-Na; Lee, Seung Ho; Khalmuratova, Roza; Park, Jong-Wan; Shin, Hyun-Woo; Choy, Young Bin

    2017-01-01

    Resveratrol (RSV) has been shown to effectively suppress chronic rhinosinusitis with nasal polyps in a mouse model; however, when locally administered to the sinonasal cavity, bolus RSV is limited by low drug bioavailability owing to its low aqueous solubility and relatively rapid clearance from the administration site. To address this limitation, we propose mucoadhesive nanostructured microparticles (PLGA/PEG NM) as a potential carrier for the sinonasal delivery of RSV. In this study, PLGA/PEG NM released RSV in a sustained manner. Owing to the enlarged specific surface area of the nanostructures, PLGA/PEG NM had synergistically enhanced mucoadhesiveness and thus showed improved in vivo retention properties in the sinonasal cavity. Therefore, when tested in a mouse nasal polyp model, PLGA/PEG NM mitigated polyp formation and restored epithelial integrity better than the control treatments. The therapeutic effect was similar at half the dose of PLGA/PEG NM, suggesting improved local bioavailability of RSV in the sinonasal cavity. PMID:28071713

  19. Mucoadhesive nanostructured lipid carriers (NLCs) as potential carriers for improving oral delivery of curcumin.

    PubMed

    Chanburee, Sanipon; Tiyaboonchai, Waree

    2017-03-01

    To examine effects of polymer types on the mucoadhesive properties of polymer-coated nanostructured lipid carriers (NLCs). Experiment: Curcumin-loaded NLCs were prepared using a warm microemulsion technique followed by coating particle surface with mucoadhesive polymers: polyethylene glycol400 (PEG400), polyvinyl alcohol (PVA), and chitosan (CS). The physicochemical properties and entrapment efficacy were examined. In vitro mucoadhesive studies were assessed by wash-off test. In addition, the stability of mucoadhesive NLCs in gastrointestinal fluids and the pattern of drug release were also investigated. The obtained nanoparticles showed spherical shape with size ranging between 200 nm and 500 nm and zeta potential between -37 and -9 mV depending on the type of polymer coating. Up to 80% drug entrapment efficacy was observed. In vitro mucoadhesive studies revealed that PEG-NLCs and PVA-NLCs were adhered strongly to freshly porcine intestinal mucosa, more than 2-fold mucoadhesive compared to CS-NLCs and uncoated-NLCs. The particle size of all polymer-coated NLCs could be maintained in both simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) suggesting good physical stability in physiological fluid. In contrast, uncoated-NLCs showed particle aggregation in SGF. In vitro dissolution studies revealed a fast release characteristic.

  20. Improved mucoadhesion and cell uptake of chitosan and chitosan oligosaccharide surface-modified polymer nanoparticles for mucosal delivery of proteins.

    PubMed

    Dyawanapelly, Sathish; Koli, Uday; Dharamdasani, Vimisha; Jain, Ratnesh; Dandekar, Prajakta

    2016-08-01

    The main aim of the present study was to compare mucoadhesion and cellular uptake efficiency of chitosan (CS) and chitosan oligosaccharide (COS) surface-modified polymer nanoparticles (NPs) for mucosal delivery of proteins. We have developed poly (D, L-lactide-co-glycolide) (PLGA) NPs, surface-modified COS-PLGA NPs and CS-PLGA NPs, by using double emulsion solvent evaporation method, for encapsulating bovine serum albumin (BSA) as a model protein. Surface modification of NPs was confirmed using physicochemical characterization methods such as particle size and zeta potential, SEM, TEM and FTIR analysis. Both surface-modified PLGA NPs displayed a slow release of protein compared to PLGA NPs. Furthermore, we have explored the mucoadhesive property of COS as a material for modifying the surface of polymeric NPs. During in vitro mucoadhesion test, positively charged COS-PLGA NPs and CS-PLGA NPs exhibited enhanced mucoadhesion, compared to negatively charged PLGA NPs. This interaction was anticipated to improve the cell interaction and uptake of NPs, which is an important requirement for mucosal delivery of proteins. All nanoformulations were found to be safe for cellular delivery when evaluated in A549 cells. Moreover, intracellular uptake behaviour of FITC-BSA loaded NPs was extensively investigated by confocal laser scanning microscopy and flow cytometry. As we hypothesized, positively charged COS-PLGA NPs and CS-PLGA NPs displayed enhanced intracellular uptake compared to negatively charged PLGA NPs. Our results demonstrated that CS- and COS-modified polymer NPs could be promising carriers for proteins, drugs and nucleic acids via nasal, oral, buccal, ocular and vaginal mucosal routes.

  1. Liposomal buccal mucoadhesive film for improved delivery and permeation of water-soluble vitamins.

    PubMed

    Abd El Azim, Heba; Nafee, Noha; Ramadan, Alyaa; Khalafallah, Nawal

    2015-07-05

    This study aims at improving the buccal delivery of vitamin B6 (VB6) as a model highly water-soluble, low permeable vitamin. Two main strategies were combined; first VB6 was entrapped in liposomes, which were then formulated as mucoadhesive film. Both plain and VB6-loaded liposomes (LPs) containing Lipoid S100 and propylene glycol (∼ 200 nm) were then incorporated into mucoadhesive film composed of SCMC and HPMC. Results showed prolonged release of VB6 (72.65%, T50% diss 105 min) after 6h from LP-film compared to control film containing free VB6 (96.37%, T50% diss 30 min). Mucoadhesion was assessed both ex vivo on chicken pouch and in vivo in human. Mucoadhesive force of 0.2N and residence time of 4.4h were recorded. Ex vivo permeation of VB6, across chicken pouch mucosa indicated increased permeation from LP-systems compared to corresponding controls. Interestingly, incorporation of the vesicles in mucoadhesive film reduced the flux by 36.89% relative to LP-dispersion. Meanwhile, both films provided faster initial permeation than the liquid forms. Correlating the cumulative percent permeated ex vivo with the cumulative percent released in vitro indicated that LPs retarded VB6 release but improved permeation. These promising results represent a step forward in the field of buccal delivery of water-soluble vitamins.

  2. Micromatricial metronidazole benzoate film as a local mucoadhesive delivery system for treatment of periodontal diseases.

    PubMed

    El-Kamel, Amal Hassan; Ashri, Lubna Y; Alsarra, Ibrahim A

    2007-09-14

    The main objective of this study was to develop a local, oral mucoadhesive metronidazole benzoate (MET) delivery system that can be applied and removed by the patient for the treatment of periodontal diseases. Mucoadhesive micromatricial chitosan/poly(epsilon-caprolactone) (CH/PCL) films and chitosan films were prepared. Thermal behavior, morphology, and particle size measurements were used to evaluate the prepared films. The effect of different molar masses of CH and different ratios of medium Mwt molar mass chitosan (MCH):PCL on water absorption, in vitro bioadhesion, mechanical properties, and in vitro drug release was examined. In vivo performance of the selected formulation was also evaluated. Differential scanning calorimetry examination revealed that MET existed mainly in amorphous form. Under microscopic examination, PCL microparticles were homogeneously dispersed in the films. The use of different molar masses of CH and different ratios of (MCH):PCL affected the size of the entrapped particles. Addition of PCL significantly decreased percentage water uptake and bioadhesion force compared with pure CH film. With regard to mechanical properties, the 2-layered film containing 1:0.625 MCH:PCL had the best tensile properties. At fixed CH:PCL ratio (1:1.25), the slowest drug release was obtained from films containing high molar mass CH. On the other hand, the 2-layered film that consisted of 1:0.625 MCH:PCL had the slowest MET release. In vivo evaluation of the selected film revealed that metronidazole concentration in saliva over 6 hours ranged from 5 to 15 microg/mL, which was within and higher than the reported range of minimum inhibitory concentration for metronidazole. A significant in vitro/in vivo correlation under the adopted experimental conditions was obtained.

  3. Mucoadhesive Amphiphilic Methacrylic Copolymer-Functionalized Poly(ε-caprolactone) Nanocapsules for Nose-to-Brain Delivery of Olanzapine.

    PubMed

    Fonseca, Francisco N; Betti, Andresa H; Carvalho, Flávia C; Gremião, Maria P D; Dimer, Frantiescoli A; Guterres, Sílvia S; Tebaldi, Marli L; Rates, Stela M K; Pohlmann, Adriana R

    2015-08-01

    Nose-to-brain drug delivery has been proposed to overcome the low absorption of drugs in central nervous system due to the absence of brain-blood barrier in the olfactory nerve pathway. However, the presence of a mucus layer and quick clearance limit the use of this route. Herein, amphiphilic methacrylic copolymer-functionalized poly(ε-caprolactone) nanocapsules were proposed as a mucoadhesive system to deliver olanzapine after intranasal administration. In vitro evaluations showed that these nanocapsules were able to interact with mucin (up to 17% of increment in particle size and 30% of reduction of particle concentration) and nasal mucosa (2-fold higher force for detaching), as well as to increase the retention of olanzapine (about 40%) on the nasal mucosa after continuous wash. The olanzapine-loaded amphiphilic methacrylic copolymer-functionalized PCL nanocapsules enhanced the amount of drug in the brain of rats (1.5-fold higher compared to the drug solution). In accordance with this finding, this formulation improved the prepulse inhibition impairment induced by apomorphine, which is considered as an operational measure of pre-attentive sensorimotor gating impairment present in schizophrenia. Besides, nanoencapsulated olanzapine did not affect the nasal mucosa integrity after repeated doses. These data evidenced that the designed nanocapsules are a promising mucoadhesive system for nose-to-brain delivery of drugs.

  4. Surface engineered nanostructured lipid carriers for efficient nose to brain delivery of ondansetron HCl using Delonix regia gum as a natural mucoadhesive polymer.

    PubMed

    Devkar, Tejas B; Tekade, Avinash R; Khandelwal, Kishanchandra R

    2014-10-01

    The objective of this investigation was to fabricate ondansetron hydrochloride [OND] loaded mucoadhesive nanostructured lipid carriers [NLCs] for efficient delivery to brain through nasal route. Mucoadhesive NLCs thereby sustaining drug release for longer time in nasal cavity. NLCs were prepared by high pressure homogenization [HPH] technique using glycerol monostearate [GMS]; as solid lipid, Capryol 90; as liquid lipid, soya lecithin; as surfactant and poloxamer 188; as cosurfactant. In the fabrication of NLCs, Delonix regia gum [DRG], isolated from seeds of D. regia belonging to family fabiaceae was used as a mucoadhesive polymer. The NLCs were evaluated for particle size, morphology, drug-entrapment efficiency [%EE], mucoadhesive strength, in vitro drug release, histological examination, ex vivo permeation study, in vivo biodistribution and pharmacokinetic studies in the brain/blood following intravenous [i.v.] and intranasal [i.n.] administration. Particle size, PDI, Zeta potential was observed in the range of 92.28-135nm, 0.32-0.46, and -11.5 to -36.2 respectively. Prepared NLCs achieved thermodynamic stability, control release pattern with minor histopathological changes in sheep nasal mucosa. The significantly [P<0.05] higher values for selected batch was observed, when administered by i.n. route showed higher drug targeting efficiency [506%] and direct transport percentage [97.14%] which confirms the development of promising OND-loaded NLC for efficient nose-to-brain delivery.

  5. Hyaluronic acid-coated niosomes facilitate tacrolimus ocular delivery: Mucoadhesion, precorneal retention, aqueous humor pharmacokinetics, and transcorneal permeability.

    PubMed

    Zeng, Weidong; Li, Qi; Wan, Tao; Liu, Cui; Pan, Wenhui; Wu, Zushuai; Zhang, Guoguang; Pan, Jingtong; Qin, Mengyao; Lin, Yuanyuan; Wu, Chuanbin; Xu, Yuehong

    2016-05-01

    Tacrolimus (FK506) was used to prevent corneal allograft rejection in patients who were resistant to steroids and cyclosporine. However, the formulation for FK506 ocular delivery remained a challenge due to the drug's high hydrophobicity, high molecular weight, and eye's physiological and anatomical constraints. The aim of this project is to develop an ocular delivery system for FK506 based on a combined strategy of niosomes and mucoadhesive hyaluronic acid (HA), i.e., FK506HA-coated niosomes, which exploits virtues of both niosomes and HA to synergistically improve ophthalmic bioavailability. The FK506HA-coated niosomes were characterized with particle size, zeta potential, and rheology behavior. Mucoadhesion of FK506HA-coated niosomes to mucin was investigated through surface plasmon resonance in comparison with non-coated niosomes and HA solution. The results showed that niosomes possessed adhesion to mucin, and HA coating enhanced the adhesion. The in vivo precorneal retention was evaluated in rabbit, and the results showed that HA-coated niosomes prolonged the residence of FK506 significantly in comparison with non-coated niosomes or suspension. Aqueous humor pharmacokinetics test showed that area under curve of HA-coated niosomes was 2.3-fold and 1.2-fold as that of suspension and non-coated niosomes, respectively. Moreover, the synergetic corneal permeability enhancement of the hybrid delivery system on FK506 was visualized and confirmed by confocal laser scanning microscope. Overall, the results indicated that the hybrid system facilitated FK506 ocular delivery on mucoadhesion, precorneal retention, aqueous humor pharmacokinetics and transcorneal permeability. Therefore, HA-coated niosomes may be a promising approach for ocular targeting delivery of FK506.

  6. Lyophilized Chitosan/xanthan Polyelectrolyte Complex Based Mucoadhesive Inserts for Nasal Delivery of Promethazine Hydrochloride

    PubMed Central

    G Dehghan, Mohamed Hassan; Marzuka, Marzuka

    2014-01-01

    The objective of this investigation was the development of chitosan/xanthan polyelectrolyte complex based mucoadhesive nasal insert of promethazine hydrochloride a drug used in the treatment of motion sickness. A 32 factorial design was applied for preparing chitosan/xanthan polyelectrolyte complex and to study the effect of independent variables i.e. concentration of xanthan [X1] and concentration of chitosan [X2] on various responses i.e. viscosity of polyelectrolyte complex solution, water uptake of nasal inserts (at pH 2, 5.5, 7.4), bioadhesion potential of nasal inserts and in-vitro drug release at Q6h through nasal inserts. FTIR and DSC analysis were carried out to confirm complex formation and on loaded and unloaded nasal insert to investigate any drug excipient interaction. The nasal inserts were also characterized by powder X-ray diffractometry (PXRD) and Scanning electron microscopy (SEM) and for ex-vivo permeation studies. The results show that higher amount of xanthan in polyelectrolyte complexes with respect to higher amount of chitosan retarded in-vitro drug release. The water uptake behaviour of nasal insert was strongly influenced by pH of the medium and by polycation/ polyanion concentration. The investigation verifies the formation of polyelectrolyte complexes formation between chitosan and xanthan at pH values in the vicinity of pKa intervals of the two polymers and confirms their potential for the nasal delivery of promethazine hydrochloride. PMID:25276178

  7. Mucoadhesion and the gastrointestinal tract.

    PubMed

    Varum, Felipe J O; McConnell, Emma L; Sousa, Joao J S; Veiga, Francisco; Basit, Abdul W

    2008-01-01

    The concept of mucoadhesion is one that has the potential to improve the highly variable residence times experienced by drugs and dosage forms at various sites in the gastrointestinal tract, and consequently, to reduce variability and improve efficacy. Intimate contact with the mucosa should enhance absorption or improve topical therapy. A variety of approaches have been investigated for mucoadhesion in the gastrointestinal tract, particularly for the stomach and small intestine. Despite interesting results in these sites, mucoadhesive approaches have not yet shown success in humans. The potential of the lower gut for these applications has been largely neglected, although the large intestine in particular may benefit, and the colon has several factors that suggest mucoadhesion could be successful there, including lower motility and the possibility of a lower mucus turnover and thicker mucus layer. In vitro studies on colonic mucoadhesion show promise, and rectal administration has shown some positive results in vivo. This review considers the background to mucoadhesion with respect to the physiological conditions of the gastrointestinal tract as well as the principles that underlie this concept. Mucoadhesive approaches to gastrointestinal drug delivery will be examined, with particular attention given to the lower gut.

  8. Vaginal delivery of paclitaxel via nanoparticles with non-mucoadhesive surfaces suppresses cervical tumor growth

    PubMed Central

    Yang, Ming; Yu, Tao; Wang, Ying-Ying; Lai, Samuel K.; Zeng, Qi; Miao, Bolong; Tang, Benjamin C.; Simons, Brian W.; Ensign, Laura; Liu, Guanshu; Chan, Kannie W. Y.; Juang, Chih-Yin; Mert, Olcay; Wood, Joseph; Fu, Jie; McMahon, Michael T.; Wu, T.-C.; Hung, Chien-Fu; Hanes, Justin

    2014-01-01

    Local delivery of chemotherapeutics in the cervicovaginal tract using nanoparticles may reduce adverse side effects associated with systemic chemotherapy, while improving outcomes for early stage cervical cancer. We hypothesize drug-loaded nanoparticles must rapidly penetrate cervicovaginal mucus (CVM) lining the female reproductive tract to effectively deliver their payload to underlying diseased tissues in a uniform and sustained manner. We develop paclitaxel-loaded nanoparticles, composed entirely of polymers used in FDA-approved products, which rapidly penetrate human CVM and provide sustained drug release with minimal burst effect. We further employ a mouse model with aggressive cervical tumors established in the cervicovaginal tract to compare paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (conventional particles , or CP) and similar particles coated with Pluronic® F127 (mucus-penetrating particles , or MPP). CP are mucoadhesive and, thus, aggregated in mucus, while MPP achieve more uniform distribution and close proximity to cervical tumors. Paclitaxel-MPP suppress tumor growth more effectively and prolong median survival of mice compared to free paclitaxel or paclitaxel-CP. Histopathological studies demonstrate minimal toxicity to the cervicovaginal epithelia, suggesting paclitaxel-MPP may be safe for intravaginal use. These results demonstrate for the first time the in vivo advantages of polymer-based MPP for treatment of tumors localized to a mucosal surface. PMID:24339398

  9. Preparation and Characterization of Gelatin-Based Mucoadhesive Nanocomposites as Intravesical Gene Delivery Scaffolds

    PubMed Central

    Liu, Ching-Wen; Chang, Li-Ching; Lin, Kai-Jen; Yu, Tsan-Jung; Tsai, Ching-Chung; Wang, Hao-Kuang; Tsai, Tong-Rong

    2014-01-01

    This study aimed to develop optimal gelatin-based mucoadhesive nanocomposites as scaffolds for intravesical gene delivery to the urothelium. Hydrogels were prepared by chemically crosslinking gelatin A or B with glutaraldehyde. Physicochemical and delivery properties including hydration ratio, viscosity, size, yield, thermosensitivity, and enzymatic degradation were studied, and scanning electron microscopy (SEM) was carried out. The optimal hydrogels (H), composed of 15% gelatin A175, displayed an 81.5% yield rate, 87.1% hydration ratio, 42.9 Pa·s viscosity, and 125.8 nm particle size. The crosslinking density of the hydrogels was determined by performing pronase degradation and ninhydrin assays. In vitro lentivirus (LV) release studies involving p24 capsid protein analysis in 293T cells revealed that hydrogels containing lentivirus (H-LV) had a higher cumulative release than that observed for LV alone (3.7-, 2.3-, and 2.3-fold at days 1, 3, and 5, resp.). Lentivirus from lentivector constructed green fluorescent protein (GFP) was then entrapped in hydrogels (H-LV-GFP). H-LV-GFP showed enhanced gene delivery in AY-27 cells in vitro and to rat urothelium by intravesical instillation in vivo. Cystometrogram showed mucoadhesive H-LV reduced peak micturition and threshold pressure and increased bladder compliance. In this study, we successfully developed first optimal gelatin-based mucoadhesive nanocomposites as intravesical gene delivery scaffolds. PMID:25580433

  10. Preparation and in vitro characterization of thermosensitive and mucoadhesive hydrogels for nasal delivery of phenylephrine hydrochloride.

    PubMed

    Xu, Xiaofeng; Shen, Yan; Wang, Wei; Sun, Chunmeng; Li, Chang; Xiong, Yerong; Tu, Jiasheng

    2014-11-01

    The aim of the present work was to develop a nasal delivery system of phenylephrine hydrochloride (PE) in spray form to make prolonged remedy of nasal congestion. The formulations contain the thermosensitive hydrogel, i.e., Poloxamer 407 (P407) and Poloxamer 188 (P188) mixtures, and mucoadhesives, i.e., ε-polylysine (ε-PL) and low molecular weight sodium hyaluronate (MW 11,000Da). The in vitro characterizations of formulations including rheology studies, texture profiles and in vitro mucoadhesion potential were investigated after gelation temperatures measurements. The results showed that the concentration of P407 or P188 had significant influence on gelation temperature and texture profiles. The addition of mucoadhesives, though lowered the gel strength of formulations, increased interaction with mucin. After screening, two formulations (i.e., 1.0% PE/0.5% ε-PL/17% P407/0.5% P188 or Formulation A; and 1.0% PE/0.5% HA/17% P407/0.8% P188 or Formulation B) presenting suitable gelation temperatures (∼32°C) were used for further studies on in vitro release behaviors and mucosa ciliotoxicity. Both formulations showed sustained release of PE for up to 8h and similar toxicity to saline, the negative control. Thus, the thermosensitive and mucoadhesive PE-containing hydrogels are promising to achieve prolonged decongestion in nasal cavity.

  11. Design, characterization, and evaluation of intranasal delivery of ropinirole-loaded mucoadhesive nanoparticles for brain targeting.

    PubMed

    Jafarieh, Omidreza; Md, Shadab; Ali, Mushir; Baboota, Sanjula; Sahni, J K; Kumari, Bhavna; Bhatnagar, Aseem; Ali, Javed

    2015-01-01

    Parkinson disease (PD) is a common, progressive neurodegenerative disorder, characterized by marked depletion of striatal dopamine and degeneration of dopaminergic neurons in the substantia nigra. The purpose of the present study was to investigate the possibility of targeting an anti-Parkinson's drug ropinirole (RH) to the brain using polymeric nanoparticles. Ropinirole hydrochloride (RH)-loaded chitosan nanoparticles (CSNPs) were prepared by an ionic gelation method. The RH-CSNPs were characterized for particle size, polydispersity index (PDI), zeta potential, loading capacity, entrapment efficiency in vitro release study, and in vivo distribution after intranasal administration. The RH-CSNPs showed sustained release profiles for up to 18 h. The RH concentrations (% Radioactivity/g) in the brain following intranasal administration (i.n.) of RH-CSNPs were found to be significantly higher at all the time points compared with RH solution. The concentration of RH was highest in the liver (7.210 ± 0.52), followed by kidneys (6.862 ± 0.62), intestine (4.862 ± 0.45), and lungs (4.640 ± 0.92) in rats following i.n. administration of RH-CSNPs. Gamma scintigraphy imaging in rats was performed to ascertain the localization of drug in the brain following intranasal administration of formulations. The brain/blood ratios obtained (0.251 ± 0.09 and 0.386 ± 0.57 of RH (i.n.) and RH-CSNPs (i.n.), respectively) at 0.5 h are indicative of direct nose to brain transport, bypassing the blood-brain barrier (BBB). The novel formulation showed the superiority of nose to brain delivery of RH using mucoadhesive nanoparticles compared with other delivery routes reported earlier.

  12. Lectin-mediated drug delivery: the second generation of bioadhesives.

    PubMed

    Lehr, C M

    2000-03-01

    This paper reviews some recent developments in the area of bioadhesive drug delivery systems. The area of bioadhesion in drug delivery had started some 20 years ago by using so-called mucoadhesive polymers. Many of these polymers were already used as excipients in pharmaceutical formulations. This has facilitated the development of the first bioadhesive drug products, which are now commercially available. A major disadvantage of the hitherto known mucoadhesives, however, is their non-specificity with respect to the substrate. In particular for gastro-intestinal applications, this may cause some premature inactivation and moreover limits the duration of mucoadhesive bonds to the relatively fast mucus turnover. Nevertheless, for some mucoadhesive polymers other interesting functionalities were discovered, such as their ability to modulate epithelial permeability and to inhibit proteolytic enzymes. In contrast to the mucoadhesive polymers, lectins and some other adhesion molecules specifically recognize receptor-like structures of the cell membrane and therefore bind directly to the epithelial cells themselves ("cytoadhesion") rather than to the mucus gel layer. Furthermore, when bioadhesion is receptor-mediated, it is not only restricted to mere binding, but may subsequently trigger the active transport of large molecules or nanoscalic drug carrier systems by vesicular transport processes (endo-/transcytosis). Rather than only acting as a platform for controlled release systems, the concept of lectin-mediated bioadhesion therefore bears the potential for the controlled delivery of macromolecular biopharmaceuticals at relevant biological barriers, such as the epithelia of the intestinal or respiratory tract.

  13. Evaluation of a mucoadhesive fenretinide patch for local intraoral delivery: a strategy to reintroduce fenretinide for oral cancer chemoprevention

    PubMed Central

    Holpuch, Andrew S.; Phelps, Maynard P.; Desai, Kashappa-Goud H.; Chen, Wei; Koutras, George M.; Han, Byungdo B.; Warner, Blake M.; Pei, Ping; Seghi, Garrett A.; Tong, Meng; Border, Michael B.; Fields, Henry W.; Stoner, Gary D.; Larsen, Peter E.; Liu, Zhongfa; Schwendeman, Steven P.; Mallery, Susan R.

    2012-01-01

    Systemic delivery of fenretinide in oral cancer chemoprevention trials has been largely unsuccessful due to dose-limiting toxicities and subtherapeutic intraoral drug levels. Local drug delivery, however, provides site-specific therapeutically relevant levels while minimizing systemic exposure. These studies evaluated the pharmacokinetic and growth-modulatory parameters of fenretinide mucoadhesive patch application on rabbit buccal mucosa. Fenretinide and blank-control patches were placed on right/left buccal mucosa, respectively, in eight rabbits (30 min, q.d., 10 days). No clinical or histological deleterious effects occurred. LC-MS/MS analyses of post-treatment samples revealed a delivery gradient with highest fenretinide levels achieved at the patch-mucosal interface (no metabolites), pharmacologically active levels in fenretinide-treated oral mucosa (mean: 5.65 μM; trace amounts of 4-oxo-4-HPR) and undetectable sera levels. Epithelial markers for cell proliferation (Ki-67), terminal differentiation (transglutaminase 1—TGase1) and glucuronidation (UDP-glucuronosyltransferase1A1—UGT1A1) exhibited fenretinide concentration-specific relationships (elevated TGase1 and UGT1A1 levels <5 μM, reduced Ki-67 indices >5μM) relative to blank-treated epithelium. All fenretinide-treated tissues showed significantly increased intraepithelial apoptosis (TUNEL) positivity, implying activation of intersecting apoptotic and differentiation pathways. Human oral mucosal correlative studies showed substantial interdonor variations in levels of the enzyme (cytochrome P450 3A4—CYP3A4) responsible for conversion of fenretinide to its highly active metabolite, 4-oxo-4-HPR. Complementary in vitro assays in human oral keratinocytes revealed fenretinide and 4-oxo-4-HPR’s preferential suppression of DNA synthesis in dysplastic as opposed to normal oral keratinocytes. Collectively, these data showed that mucoadhesive patch-mediated fenretinide delivery is a viable strategy to

  14. Evaluation of a mucoadhesive fenretinide patch for local intraoral delivery: a strategy to reintroduce fenretinide for oral cancer chemoprevention.

    PubMed

    Holpuch, Andrew S; Phelps, Maynard P; Desai, Kashappa-Goud H; Chen, Wei; Koutras, George M; Han, Byungdo B; Warner, Blake M; Pei, Ping; Seghi, Garrett A; Tong, Meng; Border, Michael B; Fields, Henry W; Stoner, Gary D; Larsen, Peter E; Liu, Zhongfa; Schwendeman, Steven P; Mallery, Susan R

    2012-05-01

    Systemic delivery of fenretinide in oral cancer chemoprevention trials has been largely unsuccessful due to dose-limiting toxicities and subtherapeutic intraoral drug levels. Local drug delivery, however, provides site-specific therapeutically relevant levels while minimizing systemic exposure. These studies evaluated the pharmacokinetic and growth-modulatory parameters of fenretinide mucoadhesive patch application on rabbit buccal mucosa. Fenretinide and blank-control patches were placed on right/left buccal mucosa, respectively, in eight rabbits (30 min, q.d., 10 days). No clinical or histological deleterious effects occurred. LC-MS/MS analyses of post-treatment samples revealed a delivery gradient with highest fenretinide levels achieved at the patch-mucosal interface (no metabolites), pharmacologically active levels in fenretinide-treated oral mucosa (mean: 5.65 μM; trace amounts of 4-oxo-4-HPR) and undetectable sera levels. Epithelial markers for cell proliferation (Ki-67), terminal differentiation (transglutaminase 1-TGase1) and glucuronidation (UDP-glucuronosyltransferase1A1-UGT1A1) exhibited fenretinide concentration-specific relationships (elevated TGase1 and UGT1A1 levels <5 μM, reduced Ki-67 indices >5 μM) relative to blank-treated epithelium. All fenretinide-treated tissues showed significantly increased intraepithelial apoptosis (TUNEL) positivity, implying activation of intersecting apoptotic and differentiation pathways. Human oral mucosal correlative studies showed substantial interdonor variations in levels of the enzyme (cytochrome P450 3A4-CYP3A4) responsible for conversion of fenretinide to its highly active metabolite, 4-oxo-4-HPR. Complementary in vitro assays in human oral keratinocytes revealed fenretinide and 4-oxo-4-HPR's preferential suppression of DNA synthesis in dysplastic as opposed to normal oral keratinocytes. Collectively, these data showed that mucoadhesive patch-mediated fenretinide delivery is a viable strategy to reintroduce

  15. Mucoadhesive amorphous solid dispersions for sustained release of poorly water soluble drugs.

    PubMed

    LaFountaine, Justin S; Prasad, Leena Kumari; Miller, Dave A; McGinity, James W; Williams, Robert O

    2017-04-01

    The oral delivery of mucoadhesive patches has been shown to enhance the absorption of large molecules such as peptides. We hypothesized that this mechanism could have utility for poorly soluble small molecules by utilizing a mucoadhesive polymer as the matrix for an amorphous solid dispersion. Binary dispersions of itraconazole and carbomer (Carbopol 71G) were prepared utilizing a thermokinetic mixing process (KinetiSol Dispersing) and the physicochemical properties were investigated by powder X-ray diffraction, calorimetry, and liquid chromatography. Adhesion of the dispersions to freshly excised porcine intestine was investigated with a texture analyzer. Minitablets were compressed from the optimal dispersion and further investigated in vitro and in vivo in rats. Thermokinetic mixing successfully processed amorphous dispersions up to 30% drug loading and each dispersion exhibited works of adhesion that were approximately an order of magnitude greater than a negative control in vitro. Ethylcellulose (EC) coated and uncoated minitablets prepared with the 30% drug load dispersion were delivered orally to rats and exhibited sustained release characteristics, with overall bioavailability greater for the uncoated minitablets compared to the EC-coated minitablets, similar to the rank order observed in our in vitro dissolution experiments. Necropsy studies showed that minitablets delivered with enteric-coated capsules targeted release to the distal small intestine and adhered to the intestinal mucosa, but the rat model presented limitations with respect to evaluating the overall performance. Based on the in vitro and in vivo results, further investigations in larger animals are a logical next step where fluid volumes, pH, and transit times are more favorable for the evaluated dosage forms.

  16. Effective mucoadhesive liposomal delivery system for risedronate: preparation and in vitro/in vivo characterization

    PubMed Central

    Jung, Il-Woo; Han, Hyo-Kyung

    2014-01-01

    In this work, we aimed to develop chitosan-coated mucoadhesive liposomes containing risedronate to improve intestinal drug absorption. Liposomes containing risedronate were prepared with 1,2-distearoryl-sn-glycero-3-phosphocholine and distearoryl-sn-glycero-3-[phospho-rac-(1-glycerol)] using the freeze-drying method, with subsequent coating of the anionic surfaces of the liposomes with chitosan. The in vitro characteristics of the chitosan-coated liposomes were investigated, including their stability, mucoadhesiveness, and Caco-2 cell permeability. This formulation was stable in simulated gastric and intestinal fluids, with the percentage of drug remaining in the liposomes being more than 90% after 24 hours of incubation. Chitosan-coated liposomes also showed strong mucoadhesive properties, implying potential electrostatic interaction with the mucous layer in the gastrointestinal tract. Compared with the untreated drug, chitosan-coated liposomes significantly enhanced the cellular uptake of risedronate, resulting in an approximately 2.1–2.6-fold increase in Caco-2 cells. Further, the chitosan-coated liposomes increased the oral exposure of risedronate by three-fold in rats. Taken together, the results of this study suggest that chitosan-coated liposomes containing risedronate should be effective for improving the bioavailability of risedronate. PMID:24872692

  17. Effects of the mucoadhesive polymer polycarbophil on the intestinal absorption of a peptide drug in the rat.

    PubMed

    Lehr, C M; Bouwstra, J A; Kok, W; De Boer, A G; Tukker, J J; Verhoef, J C; Breimer, D D; Junginger, H E

    1992-05-01

    The absorption across rat intestinal tissue of the model peptide drug 9-desglycinamide, 8-arginine vasopressin from bioadhesive formulations was studied in-vitro, in a chronically isolated internal loop in-situ and after intraduodenal administration in-vivo. A controlled-release bioadhesive drug delivery system was tested, consisting of microspheres of poly(2-hydroxyethyl methacrylate) with a mucoadhesive Polycarbophil-coating, as well as fast-release formulation consisting of an aqueous solution of the peptide in a suspension of Polycarbophil particles. Using the controlled-release system, a slight improvement of peptide absorption was found in-vitro in comparison with a non-adhesive control system, but not in-situ or in-vivo. In contrast, bioavailability was significantly increased in all three models from the Polycarbophil suspension in comparison with a solution of the drug in saline. The effect appeared to be dose-dependent, indicative of intrinsic penetration-enhancing properties of the mucoadhesive polymer. A prolongation of the absorption phase in-vitro and in the chronically isolated loop in-situ suggested that the polymer was able to protect the peptide from proteolytic degradation. This could be confirmed by degradation studies in-vitro. The duration of the penetration enhancing/enzyme inhibiting effect was diminished with increasing complexity of the test model, in the same way as was previously found for the bioadhesive effect. This interrelationship suggests that the observed improvement in peptide absorption and the mucoadhesive properties of this polymer are associated. The development of a fast-release oral dosage form for peptide drugs on the basis of Polycarbophil appears to be possible.

  18. Thermally triggered mucoadhesive in situ gel of loratadine: β-cyclodextrin complex for nasal delivery.

    PubMed

    Singh, Reena M P; Kumar, Anil; Pathak, Kamla

    2013-03-01

    The aim of the present study was to increase the solubility of an anti-allergic drug loratadine by making its inclusion complex with β-cyclodextrin and to develop it's thermally triggered mucoadhesive in situ nasal gel so as to overcome first-pass effect and consequently enhance its bioavailability. A total of eight formulations were prepared by cold method and optimized by 2(3) full factorial design. Independent variables (concentration of poloxamer 407, concentration of carbopol 934 P, and pure drug or its inclusion complex) were optimized in order to achieve desired gelling temperature with sufficient mucoadhesive strength and maximum permeation across experimental nasal membrane. The design was validated by extra design checkpoint formulation (F9) and Pareto charts were used to help eliminate terms that did not have a statistically significant effect. The response surface plots and possible interactions between independent variables were analyzed using Design Expert Software 8.0.2 (Stat Ease, Inc., USA). Faster drug permeation with zero-order kinetics and target flux was achieved with formulation containing drug: β-cyclodextrin complex rather than those made with free drug. The optimized formulation (F8) with a gelling temperature of 28.6±0.47°C and highest mucoadhesive strength of 7,676.0±0.97 dyn/cm2 displayed 97.74±0.87% cumulative drug permeation at 6 h. It was stable for over 3 months and histological examination revealed no remarkable damage to the nasal tissue.

  19. Formulation and characterization of intranasal mucoadhesive nanoparticulates and thermo-reversible gel of levodopa for brain delivery.

    PubMed

    Sharma, Sumit; Lohan, Shikha; Murthy, R S R

    2014-07-01

    Levodopa is the drug of choice in the treatment of Parkinson's disease but it exhibits low oral bioavailability (30%) and very low brain uptake due to its extensive metabolism by aromatic amino acid decarboxylase in the peripheral circulation. Hence, levodopa is co-administered with carbidopa, a peripheral amino acid decarboxylase inhibitor. In an attempt to improve brain uptake and to avoid degradation of levodopa in peripheral circulation and the use of carbidopa in combination, nose to brain drug delivery of levodopa alone via the olfactory route and the trigeminal nerves has been investigated. Chitosan nanoparticles loaded with levodopa (CNL) were prepared and were incorporated in a thermo-reversible gel prepared using Pluronic PF127 (CNLPgel). The preparation of CNL and CNLPgel was optimized for formulation parameters such as chitosan:TPP ratio, drug load Pluronic concentration to obtain desired particle size of CNL, gelling temperature, gelling time and mucoadhesive strength of CNLPgel. Rheological studies indicated a change in the rheological behavior of plain pluronic gel from Newtonian system at 30 °C to pseudoplastic behavior at 35 °C on incorporation of CNL. In vitro release studies from CNL obeyed Higuchi kinetic model, whereas the drug release from CNLPgel followed the Hixson-Crowell model. In vivo studies indicated a maximum recovery of the drug in brain following intranasal administration of CNL suspension in saline closely followed by the drug dispersed in plain pluronic gel.

  20. Mollusk glue inspired mucoadhesives for biomedical applications.

    PubMed

    Xu, Jinke; Soliman, Ghareb M; Barralet, Jake; Cerruti, Marta

    2012-10-02

    Chitosan (CH), partially N-deacetylated chitin, is a biodegradable and biocompatible polymer that has shown great potential in drug delivery and tissue engineering applications. Although bioadhesive, CH has limited mucoadhesion in wet conditions due to weak interactions with biological surfaces. DOPA (3,4-dihydroxy-L-phenylalanine), a catechol-containing molecule naturally present in marine mussel foot proteins, has been shown to increase the mucoadhesion of several polymers. We report here a simple and bioinspired approach to enhance CH mucoadhesion in wet conditions by preparing mixed hydrogels including CH and different catechol-containing compounds, namely DOPA, hydrocaffeic acid (HCA), and dopamine (DA). We characterized the hydrogels for their swelling, release kinetics of the catechol compounds, and mucoadhesive strength to rabbit small intestine. The swelling of the hydrogels was pH dependent with maximum swelling at pH 1. The hydrogel swelling was higher in the presence of the DOPA and DA but lower in the presence of HCA. HCA/CH hydrogel also showed the slowest catechol release, most likely due to electrostatic interactions between CH and HCA. Lower hydrogel swelling and slower HCA release resulted in increased mucoadhesion: HCA/CH showed more than 2-fold enhancement of mucoadhesion to rabbit small intestine compared to CH alone. Since it is known that catechol compounds can be oxidized, we analyzed the oxidation of DOPA, HCA, and DA at different pH values and its effect on mucoadhesion. We found that oxidation occurring before contact with the intestinal mucosa did not improve mucoadhesion, while oxidation occurring during the contact further increased the mucoadhesion of HCA/CH hydrogels. These results show that mucoadhesion of CH hydrogels can be increased with a simple bioinspired approach, which has the potential to be applied to other polymers since it does not require any chemical modification.

  1. Smart Polymers in Nasal Drug Delivery

    PubMed Central

    Chonkar, Ankita; Nayak, Usha; Udupa, N.

    2015-01-01

    Nasal drug delivery has now been recognized as a promising route for drug delivery due to its capability of transporting a drug to systemic circulation and central nervous system. Though nasal mucosa offers improved bioavailability and quick onset of action of the drug, main disadvantage associated with nasal drug delivery is mucocilliary clearance due to which drug particles get cleared from the nose before complete absorption through nasal mucosa. Therefore, mucoadhesive polymeric approach can be successfully used to enhance the retention of the drug on nasal mucosal surface. Here, some of the aspects of the stimuli responsive polymers have been discussed which possess liquid state at the room temperature and in response to nasal temperature, pH and ions present in mucous, can undergo in situ gelation in nasal cavity. In this review, several temperature responsive, pH responsive and ion responsive polymers used in nasal delivery, their gelling mechanisms have been discussed. Smart polymers not only able to enhance the retention of the drug in nasal cavity but also provide controlled release, ease of administration, enhanced permeation of the drug and protection of the drug from mucosal enzymes. Thus smart polymeric approach can be effectively used for nasal delivery of peptide drugs, central nervous system dugs and hormones. PMID:26664051

  2. Tragacanth as an oral peptide and protein delivery carrier: Characterization and mucoadhesion.

    PubMed

    Nur, M; Ramchandran, L; Vasiljevic, T

    2016-06-05

    Biopolymers such as tragacanth, an anionic polysaccharide gum, can be alternative polymeric carrier for physiologically important peptides and proteins. Characterization of tragacanth is thus essential for providing a foundation for possible applications. Rheological studies colloidal solution of tragacanth at pH 3, 5 or 7 were carried out by means of steady shear and small amplitude oscillatory measurements. Tragacanth mucoadhesivity was also analyzed using an applicable rheological method and compared to chitosan, alginate and PVP. The particle size and zeta potential were measured by a zetasizer. Thermal properties of solutions were obtained using a differential scanning calorimetry. The solution exhibited shear-thinning characteristics. The value of the storage modulus (G') and the loss modulus (G″) increased with an increase in angular frequency (Ω). In all cases, loss modulus values were higher than storage values (G″>G') and viscous character was, therefore, dominant. Tragacanth and alginate showed a good mucoadhesion. Tragacanth upon dispersion created particles of a submicron size with a negative zeta potential (-7.98 to -11.92 mV). These properties were pH dependant resulting in acid gel formation at pH 3.5. Tragacanth has thus a potential to be used as an excipient for peptide/protein delivery.

  3. Tapioca starch blended alginate mucoadhesive-floating beads for intragastric delivery of Metoprolol Tartrate.

    PubMed

    Biswas, Nikhil; Sahoo, Ranjan Kumar

    2016-02-01

    The objective of the study was to develop tapioca starch blended alginate mucoadhesive-floating beads for the intragastric delivery of Metoprolol Tartrate (MT). The beads were prepared by ionotropic gelation method using calcium chloride as crosslinker and gas forming calcium carbonate (CaCO3) as floating inducer. The alginate gel beads having 51-58% entrapped MT showed 90% release within 45 min in gastric medium (pH 1.2). Tapioca starch blending markedly improved the entrapment efficiency (88%) and sustained the release for 3-4 h. A 12% w/w HPMC coating on these beads extended the release upto 9-11 h. In vitro wash off and buoyancy test in gastric media revealed that the beads containing CaCO3 has gastric residence of more than 12 h. In vitro optimized multi-unit formulation consisting of immediate and sustained release mucoadhesive-floating beads (40:60) showed good initial release of 42% MT within 1h followed by a sustained release of over 90% for 11 h. Pharmacokinetic study performed in rabbit model showed that the relative oral bioavailability of MT after administration of oral solution, sustain release and optimized formulation was 51%, 67% and 87%, respectively. Optimized formulation showed a higher percent inhibition of isoprenaline induced heart rate in rabbits for almost 12 h.

  4. Lyophilized mucoadhesive-dendrimer enclosed matrix tablet for extended oral delivery of albendazole.

    PubMed

    Mansuri, Shakir; Kesharwani, Prashant; Tekade, Rakesh Kumar; Jain, Narendra Kumar

    2016-05-01

    Dendrimers are multifunctional carriers widely employed for delivering drugs in a variety of disease conditions including HIV/AIDS and cancer. Albendazole (ABZ) is a commonly used anthelmintic drug in human as well as veterinary medicine. In this investigation, ABZ was formulated as a "muco-dendrimer" based sustained released tablet. The mucoadhesive complex was synthesized by anchoring chitosan to fifth generation PPI dendrimer (Muco-PPI) and characterized by UV, FTIR, (1)H NMR spectroscopy and electron microscopy. ABZ was entrapped inside Muco-PPI followed by lyophilization and tableting as matrix tablet. A half-life (t1/2) of 8.06±0.15, 8.17±0.47, 11.04±0.73, 11.49±0.92, 12.52±1.04 and 16.9±1.18h was noted for ABZ (free drug), conventional ABZ tablet (F1), conventional ABZ matrix tablet (F2), PPI-ABZ complex, PPI-ABZ matrix tablet (F3) and Muco-PPI-ABZ matrix tablet (F4), respectively. Thus the novel mucoadhesive-PPI based formulation of ABZ (F4) increased the t1/2 of ABZ significantly by almost twofold as compared to the administration of free drug. The in vivo drug release data showed that the Muco-PPI based formulations have a significantly higher Cmax (2.40±0.02μg/mL) compared with orally administered free ABZ (0.19±0.07μg/mL) as well as conventional tablet (0.20±0.05μg/mL). In addition, the Muco-PPI-ABZ matrix tablet displayed increased mean residence time (MRT) and is therefore a potential candidate to appreciably improve the pharmacokinetic profile of ABZ. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Recent advances in ophthalmic drug delivery

    PubMed Central

    Kompella, Uday B; Kadam, Rajendra S; Lee, Vincent HL

    2011-01-01

    Topical ocular drug bioavailability is notoriously poor, in the order of 5% or less. This is a consequence of effective multiple barriers to drug entry, comprising nasolacrimal drainage, epithelial drug transport barriers and clearance from the vasculature in the conjunctiva. While sustained drug delivery to the back of the eye is now feasible with intravitreal implants such as Vitrasert™ (~6 months), Retisert™ (~3 years) and Iluvien™ (~3 years), currently there are no marketed delivery systems for long-term drug delivery to the anterior segment of the eye. The purpose of this article is to summarize the resurgence in interest to prolong and improve drug entry from topical administration. These approaches include mucoadhesives, viscous polymer vehicles, transporter-targeted prodrug design, receptor-targeted functionalized nanoparticles, iontophoresis, punctal plug and contact lens delivery systems. A few of these delivery systems might be useful in treating diseases affecting the back of the eye. Their effectiveness will be compared against intravitreal implants (upper bound of effectiveness) and trans-scleral systems (lower bound of effectiveness). Refining the animal model by incorporating the latest advances in microdialysis and imaging technology is key to expanding the knowledge central to the design, testing and evaluation of the next generation of innovative ocular drug delivery systems. PMID:21399724

  6. Transmucosal macromolecular drug delivery.

    PubMed

    Prego, C; García, M; Torres, D; Alonso, M J

    2005-01-03

    Mucosal surfaces are the most common and convenient routes for delivering drugs to the body. However, macromolecular drugs such as peptides and proteins are unable to overcome the mucosal barriers and/or are degraded before reaching the blood stream. Among the approaches explored so far in order to optimize the transport of these macromolecules across mucosal barriers, the use of nanoparticulate carriers represents a challenging but promising strategy. The present paper aims to compare the characteristics and potential of nanostructures based on the mucoadhesive polysaccharide chitosan (CS). These are CS nanoparticles, CS-coated oil nanodroplets (nanocapsules) and CS-coated lipid nanoparticles. The characteristics and behavior of CS nanoparticles and CS-coated lipid nanoparticles already reported [A. Vila, A. Sanchez, M. Tobio, P. Calvo, M.J. Alonso, Design of biodegradable particles for protein delivery, J. Control. Rel. 78 (2002) 15-24; R. Fernandez-Urrusuno, P. Calvo, C. Remunan-Lopez, J.L. Vila-Jato, M.J. Alonso, Enhancement of nasal absorption of insulin using chitosan nanoparticles, Pharm. Res. 16 (1999) 1576-1581; M. Garcia-Fuentes, D. Torres, M.J. Alonso, New surface-modified lipid nanoparticles as delivery vehicles for salmon calcitonin (submitted for publication).] are compared with those of CS nanocapsules originally reported here. The three types of systems have a size in the nanometer range and a positive zeta potential that was attributed to the presence of CS on their surface. They showed an important capacity for the association of peptides such as insulin, salmon calcitonin and proteins, such as tetanus toxoid. Their mechanism of interaction with epithelia was investigated using the Caco-2 model cell line. The results showed that CS-coated systems caused a concentration-dependent reduction in the transepithelial resistance of the cell monolayer. Moreover, within the range of concentrations investigated, these systems were internalized in the

  7. Chitosan-catechol: a polymer with long-lasting mucoadhesive properties.

    PubMed

    Kim, Kyuri; Kim, Keumyeon; Ryu, Ji Hyun; Lee, Haeshin

    2015-06-01

    Numerous mucoadhesive polymers have been exploited for prolonging the residence time of formulated drugs or pharmaceuticals at specific delivery sites. However, it has been difficult to achieve satisfactory mucoadhesive properties. The two major modification strategies such as thiolation or lectin functionalization have been extensively studied, but disulfide bond reversibility in the case of thiolation and the toxicity of lectins have been problems. Thus, approaches for further improvement of mucoadhesive properties need to be developed. With an overwhelming library of mucoadhesive polymers, one practical way to improve mucoadhesion is chemical modification of existing mucoadhesive polymers. In other words, the method is based on utilizing the cooperative effect that might be achieved by chemical tethering of a small adhesive moiety to an available mucoadhesive polymer. Here, we conjugated catechols derived from mussel adhesive proteins to chitosan, which is a widely known mucoadhesive polymer. We demonstrated that the gastrointestinal (GI) tract retention of chitosan-catechol was improved compared to unmodified chitosan, which is due to the formation of irreversible catechol mediated-crosslinking with mucin. The results indicate that catechol modification of mucoadhesive polymers may possibly lead to a new generation of mucoadhesive polymers for mucosal drug delivery.

  8. Mucosa-plate for direct evaluation of mucoadhesion of drug carriers.

    PubMed

    Tachaprutinun, Amornset; Pan-In, Porntip; Wanichwecharungruang, Supason

    2013-01-30

    The method to prepare mucosa-plates, glass slides covalently coated with mucin, is demonstrated. The use of the plate to evaluate mucoadhesion of nanocarriers made from different four polymeric materials, N-succinylchitosan (NS-chitosan), alginate (ALG), ethylcellulose (EC), and a blend of EC and methylcellulose (EC/MC), was demonstrated. While different mucoadhesion of the four carriers could be detected using mucosa-plate, the conventional viscosity measurement could not differentiate their mucin-binding ability. ALG and NS-chitosan nanospheres showed the best attachment to the mucosa-plate compared to the EC/MC and EC spheres. Capsaicin, a model hydrophobic drug, was loaded into the carriers and the ability of the different polymeric carriers to retain capsaicin at the stomach tissue was compared using an ex vivo fresh porcine stomach assay. Ability to retain capsaicin at the stomach tissue correlated well with binding affinity toward the mucosa-plate and the loading capacity of the carriers.

  9. Evaluation of TRI-726 as a drug delivery matrix.

    PubMed

    Mondal, Pravakar; Alur, Hemant H; Johnston, Thomas P

    2011-08-01

    The TRI-726 polymeric drug delivery matrix is a newly-developed biocompatible hydrogel exhibiting in situ reverse-thermal gelling, mucoadhesivity, and sustained-erosion properties. Using two model drugs, clindamycin hydrochloride and acetaminophen, we determined the gelling temperatures, in vitro release profiles, kinetics of matrix erosion, rheological properties, mucoadhesive strength, microbiological activity of released clindamycin, and biocompatibility when in contact with cells. It was demonstrated that none of the excipients contained in the TRI-726 polymer matrix caused any loss in clindamycin?s antimicrobial activity following incorporation into the polymer matrix. Thus, the new patent pending TRI-726 drug delivery matrix was both inert and non-reactive toward the incorporated clindamycin in terms of chemical degradation (< 10% degradation under accelerated conditions over 6 months) and antimicrobial activity. This new drug delivery matrix is capable of releasing a wide variety of water-soluble drug compounds over an approximate 10-day period, due primarily to protracted dissolution/erosion of the three-dimensional polymer matrix in an aqueous-based biophase. Additionally, TRI-726 exhibits excellent mucoadhesive properties that would allow a candidate drug/TRI-726 formulation to adhere and remain at a potential application site for an extended period of time. Lastly, the biocompatibility tests affirmed the non-toxic and biocompatible nature of TRI-726 when in contact with cells, which suggests its suitability and versatility as a drug delivery matrix for the targeted administration of a wide range of pharmaceutical compounds where in situ gelation, protracted release of the active, and mucoadhesion of the formulation are desired.

  10. [A novel anticancer drug delivery system -DAC-70/CDDP].

    PubMed

    Sugitachi, Akio; Otsuka, Koki; Fujisawa, Kentaro; Itabashi, Tetsuya; Akiyama, Yuji; Sasaki, Akira; Ikeda, Kenichiro; Yoshida, Yasuo; Takamori, Yoshimori; Kurozumi, Seiji; Mori, Takatoshi; Wakabayashi, Go

    2007-11-01

    We devised a muco-adhesive anticancer drug delivery system using 70% deacetylated chitin (DAC-70) and cisplatin (CDDP) and 5-fluorouracil (5-FU). The adhesive force between the system and human colonic mucosa was measured ex vivo, and a release profile of each drug was examined in vitro. Each system demonstrated a stronger muco-adhesive force at 37 degrees C than that of 25 degrees C. The CDDP-loaded system showed a sustained release of the drug while the 5-FU-loaded system exhibited an initial bursting of the agent. We presume that the release profile of CDDP and 5-FU is closely related to both degradability of the chitin and interactions between the chitin and each drug. The DAC-70/CDDP system would be clinically promising in loco-regional cancer chemotherapy.

  11. Chitosan nanoparticles for oral drug and gene delivery

    PubMed Central

    Bowman, Katherine; Leong, Kam W

    2006-01-01

    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. PMID:17722528

  12. A new approach in gastroretentive drug delivery system using cholestyramine.

    PubMed

    Umamaheshwari, R B; Jain, Subheet; Jain, N K

    2003-01-01

    We prepared cellulose acetate butyrate (CAB)-coated cholestyramine microcapsules as a intragastric floating drug delivery system endowed with floating ability due to the carbon dioxide generation when exposed to the gastric fluid. The microcapsules also have a mucoadhesive property. Ion-exchange resin particles can be loaded with bicarbonate followed by acetohydroxamic acid (AHA) and coated with CAB by emulsion solvent evaporation method. The drug concentration was monitored to maintain the floating property and minimum effective concentration. The effect of CAB: drug-resin ratio (2:1, 4:1, 6:1 w/w) on the particle size, floating time, and drug release was determined. Cholestyramine microcapsules were characterized for shape, surface characteristics, and size distribution; cholestyramine/acetohydroxamic acid interactions inside microcapsules were investigated by X-ray diffractometry. The buoyancy time of CAB-coated formulations was better than that of uncoated resin particles. Also, a longer floating time was observed with a higher polymer:drug resin complex ratio (6:1). With increasing coating thickness the particle size was increased but drug release rate was decreased. The drug release rate was higher in simulated gastric fluid (SGF) than in simulated intestinal fluid (SIF). The in vivo mucoadhesion studies were performed with rhodamine-isothiocyanate (RITC) by fluorescent probe method. The amount of CAB-coated cholestyramine microcapsules that remained in the stomach was slightly lower than that of uncoated resin particles. Cholestyramine microcapsules were distributed throughout the stomach and exhibited prolonged gastric residence via mucoadhesion. These results suggest that CAB-coated microcapsules could be a floating as well as a mucoadhesive drug delivery system. Thus, it has promise in the treatment of Helicobacter pylori.

  13. Overview on gastroretentive drug delivery systems for improving drug bioavailability.

    PubMed

    Lopes, Carla M; Bettencourt, Catarina; Rossi, Alessandra; Buttini, Francesca; Barata, Pedro

    2016-08-20

    In recent decades, many efforts have been made in order to improve drug bioavailability after oral administration. Gastroretentive drug delivery systems are a good example; they emerged to enhance the bioavailability and effectiveness of drugs with a narrow absorption window in the upper gastrointestinal tract and/or to promote local activity in the stomach and duodenum. Several strategies are used to increase the gastric residence time, namely bioadhesive or mucoadhesive systems, expandable systems, high-density systems, floating systems, superporous hydrogels and magnetic systems. The present review highlights some of the drugs that can benefit from gastroretentive strategies, such as the factors that influence gastric retention time and the mechanism of action of gastroretentive systems, as well as their classification into single and multiple unit systems.

  14. Mucoadhesion on urinary bladder mucosa: the influence of sodium, calcium, and magnesium ions.

    PubMed

    Kos, M Kerec; Bogataj, M; Mrhar, A

    2010-07-01

    The aim of the present work was to establish if different cations present in the lumen of the urinary bladder at the time of application affect the mucoadhesion strength of cationic chitosan, anionic sodium carboxymethyl cellulose (NaCMC), and nonionic hydroxypropyl cellulose (HPC). The mucoadhesion strength of polymeric films was determined on pig urinary bladder mucosa. Sodium, calcium, and magnesium ions decreased the mucoadhesion strength of all three polymers except NaCMC, whose detachment forces were not influenced by the presence of sodium. Lower mucoadhesion strength in the presence of cations should be considered when drug delivery systems, for example microspheres, containing the tested mucoadhesive polymers are applied intravesically. In the majority of the experiments, cations decreased the mucoadhesion strength of the polymers already in concentrations normally present in urine. For stronger mucoadhesion, application of microspheres into the empty urinary bladder would be recommended. Additionally, the mucoadhesion properties of the tested polymers could be controlled by the selection of a proper medium for the suspension of microspheres. Namely, for all three polymers bivalent calcium and magnesium had stronger influence on mucoadhesion compared to univalent sodium, and with increasing concentrations of cations mucoadhesion strength of the polymers decreased.

  15. Advances in chitosan-based drug delivery vehicles

    NASA Astrophysics Data System (ADS)

    Hu, Liming; Sun, Yun; Wu, Yan

    2013-03-01

    Within the past few years, chitosan-based drug delivery vehicles have become some of the most attractive to be studied. In contrast to all other polysaccharides, chitosan has demonstrated its unique characteristics for drug delivery platforms, including its active primary amino groups for chemical modification, simple and mild preparation methods for the encapsulation of biomolecules or drugs, mucoadhesion to facilitate transport across mucosal barriers and so on. In this review, an overview of the various types of chitosan-based drug delivery systems is provided, with special focus on polymeric drug conjugates and drug nanocarriers. The first part of the review is concerned with the development and applications of polymeric chitosan-drug conjugates. Then the chitosan-based nanocarrier systems as well as their preparation methods and applications are further discussed.

  16. Buccal drug delivery.

    PubMed

    Smart, John D

    2005-05-01

    Buccal formulations have been developed to allow prolonged localised therapy and enhanced systemic delivery. The buccal mucosa, however, while avoiding first-pass effects, is a formidable barrier to drug absorption, especially for biopharmaceutical products (proteins and oligonucleotides) arising from the recent advances in genomics and proteomics. The buccal route is typically used for extended drug delivery, so formulations that can be attached to the buccal mucosa are favoured. The bioadhesive polymers used in buccal drug delivery to retain a formulation are typically hydrophilic macro-molecules containing numerous hydrogen bonding groups. Newer second-generation bioadhesives have been developed and these include modified or new polymers that allow enhanced adhesion and/or drug delivery, in addition to site-specific ligands such as lectins. Over the last 20 years a wide range of formulations has been developed for buccal drug delivery (tablet, patch, liquids and semisolids) but comparatively few have found their way onto the market. Currently, this route is restricted to the delivery of a limited number of small lipophilic molecules that readily cross the buccal mucosa. However, this route could become a significant means for the delivery of a range of active agents in the coming years, if the barriers to buccal drug delivery are overcome. In particular, patient acceptability and the successful systemic delivery of large molecules (proteins, oligonucleotides and polysaccharides) via this route remains both a significant opportunity and challenge, and new/improved technologies may be required to address these.

  17. Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaluronic acid and chitosan.

    PubMed

    Lim, S T; Martin, G P; Berry, D J; Brown, M B

    2000-05-15

    Rapid mucociliary clearance of intranasally administered drugs is often a key factor in determining the bioavailability of such therapeutic agents. The use of mucoadhesive microparticles provide a potential strategy for improving retention of drugs within the nasal cavity, and thereby improve the resultant pharmacokinetic profile. This study describes the comparison of a number of novel, potentially mucoadhesive microspheres, prepared by solvent evaporation, composed of hyaluronic acid (HA), chitosan glutamate (CH) and a combination of the two with microcapsules of HA and gelatin prepared by complex coacervation. The microspheres had a mean particle size of 19.91+/-1.57 microm (HA), 28.60+/-1.34 microm (HA/CH), 29.47+/-3.58 microm (CH). The incorporation of a model drug, gentamicin sulphate (%) was 46.90+/-0.53 (HA), 28.04+/-1.21 (HA/CH) and 13.32+/-1.04 (CH). The in vitro release profiles of microsphere formulations prepared by solvent evaporation were determined. The release of gentamicin from HA and HA/CH was 50% longer than CH and was best modelled as a release from a matrix. The degree of mucoadhesion of each formulation was investigated by determining the mucociliary transport rate (MTR) of the microparticles across an isolated frog palate. Acacia/gelatin microcapsules were used as a positive control. The rank order of mucoadhesion for the microspheres and the microparticles was HA=HA/CH>CH>HA/gelatin>CHins. The entrapment of gentamicin did not affect the mucoadhesive properties (P>0.05, Mann--Whitney U-test). The combination of HA with chitosan may afford additional advantages in combining the mucoadhesive potential of HA with the penetration enhancing effect of chitosan.

  18. Mucoadhesion and drug permeability of free mixed films of pectin and chitosan: an in vitro and ex vivo study.

    PubMed

    Hagesaether, Ellen; Hiorth, Marianne; Sande, Sverre Arne

    2009-02-01

    The objective of this study was to identify the important factors for the drug permeability and mucoadhesion of casted free pectin/chitosan combination films. The factors varied were: the type of pectin (low and high methoxyl pectin) and the ratio pectin:chitosan (25:75, 50:50 and 75:25). The model drug used for measuring drug permeability was paracetamol. A texture analyzer was used for measuring mucoadhesion by using two different setups: (1) in vitro tensile tests measuring the detachment force of films versus a mucin dispersion and (2) ex vivo shear tests measuring the friction forces between pre-hydrated films and fresh porcine small intestine, with the system immersed in phosphate buffer, pH 6.8. The type of pectin used in the combination films did not have a significant effect on the drug permeability. The ex vivo mucoadhesion test revealed significant differences between low and high methoxyl pectin only for the 50:50 pectin:chitosan films. For that type of film, the peak and friction forces were highest for high methoxyl pectin. Both the mucoadhesion and drug permeability generally increased with decreasing amounts of pectin relative to chitosan in the films.

  19. Intracochlear Drug Delivery Systems

    PubMed Central

    Borenstein, Jeffrey T.

    2011-01-01

    Introduction Advances in molecular biology and in the basic understanding of the mechanisms associated with sensorineural hearing loss and other diseases of the inner ear, are paving the way towards new approaches for treatments for millions of patients. However, the cochlea is a particularly challenging target for drug therapy, and new technologies will be required to provide safe and efficacious delivery of these compounds. Emerging delivery systems based on microfluidic technologies are showing promise as a means for direct intracochlear delivery. Ultimately, these systems may serve as a means for extended delivery of regenerative compounds to restore hearing in patients suffering from a host of auditory diseases. Areas covered in this review Recent progress in the development of drug delivery systems capable of direct intracochlear delivery is reviewed, including passive systems such as osmotic pumps, active microfluidic devices, and systems combined with currently available devices such as cochlear implants. The aim of this article is to provide a concise review of intracochlear drug delivery systems currently under development, and ultimately capable of being combined with emerging therapeutic compounds for the treatment of inner ear diseases. Expert Opinion Safe and efficacious treatment of auditory diseases will require the development of microscale delivery devices, capable of extended operation and direct application to the inner ear. These advances will require miniaturization and integration of multiple functions, including drug storage, delivery, power management and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for treatment of these diseases. PMID:21615213

  20. Hydrogel nanoparticles and nanocomposites for nasal drug/vaccine delivery.

    PubMed

    Salatin, Sara; Barar, Jaleh; Barzegar-Jalali, Mohammad; Adibkia, Khosro; Milani, Mitra Alami; Jelvehgari, Mitra

    2016-09-01

    Over the past few years, nasal drug delivery has attracted more and more attentions, and been recognized as the most promising alternative route for the systemic medication of drugs limited to intravenous administration. Many experiments in animal models have shown that nanoscale carriers have the ability to enhance the nasal delivery of peptide/protein drugs and vaccines compared to the conventional drug solution formulations. However, the rapid mucociliary clearance of the drug-loaded nanoparticles can cause a reduction in bioavailability percentage after intranasal administration. Thus, research efforts have considerably been directed towards the development of hydrogel nanosystems which have mucoadhesive properties in order to maximize the residence time, and hence increase the period of contact with the nasal mucosa and enhance the drug absorption. It is most certain that the high viscosity of hydrogel-based nanosystems can efficiently offer this mucoadhesive property. This update review discusses the possible benefits of using hydrogel polymer-based nanoparticles and hydrogel nanocomposites for drug/vaccine delivery through the intranasal administration.

  1. Novel tamarind seed polysaccharide-alginate mucoadhesive microspheres for oral gliclazide delivery: in vitro-in vivo evaluation.

    PubMed

    Pal, Dilipkumar; Nayak, Amit Kumar

    2012-04-01

    Novel tamarind seed polysaccharide (TSP)-alginate mucoadhesive microspheres were prepared using TSP and alginate as blend in different ratios with different calcium chloride (CaCl(2)) concentration as a cross linker by ionotropic gelation. The prepared microspheres were of spherical shape having rough surfaces, and average particle sizes within the range of 752.12 ± 6.42 to 948.49 ± 20.92 µm. The drug entrapment efficiency of these microspheres were within the range between 58.12 ± 2.42 to 82.78 ± 3.43% w/w. Fourier transform infrared (FTIR) studies indicated that there were no reactions between gliclazide, and polymers (TSP, and sodium alginate) used. Different formulations of gliclazide loaded TSP-alginate microspheres showed prolonged in vitro release profiles of gliclazide over 12 hours in both stomach pH (pH 1.2), and intestinal pH (pH 7.4). It was found that the gliclazide release in gastric pH was comparatively slow and sustained than intestinal pH. These TSP-alginate microspheres also exhibited good mucoadhesivity. The in vivo studies on alloxan-induced diabetic rats (Animal Ethical Committee registration number: IFTM/837ac/0160) demonstrated the significant hypoglycemic effect of selected formulation of TSP-alginate mucoadhesive microspheres containing gliclazide on oral administration. This developed gliclazide loaded new TSP-alginate mucoadhesive microspheres may be very much useful for prolonged systemic absorption of gliclazide for proper maintaining blood glucose level and advanced patient compliance.

  2. Sublingual drug delivery.

    PubMed

    Goswami, Tarun; Jasti, Bhaskara; Li, Xiaoling

    2008-01-01

    The sublingual route is one of the early modes of administration for systemic drug delivery. This route avoids first-pass metabolism and affords quick drug entry into the systemic circulation. Attempts have been made to deliver various pharmacologically active agents, such as cardiovascular drugs, analgesics, and peptides, across the sublingual mucosa. In this review, the anatomical structure, blood supply, biochemical composition, transport pathways, permeation enhancement strategies, in vitro/in vivo models, and clinical investigations for the sublingual route of drug delivery is discussed.

  3. Advanced drug delivery approaches against periodontitis.

    PubMed

    Joshi, Deeksha; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    Periodontitis is an inflammatory disease of gums involving the degeneration of periodontal ligaments, creation of periodontal pocket and resorption of alveolar bone, resulting in the disruption of the support structure of teeth. According to WHO, 10-15% of the global population suffers from severe periodontitis. The disease results from the growth of a diverse microflora (especially anaerobes) in the pockets and release of toxins, enzymes and stimulation of body's immune response. Various local or systemic approaches were used for an effective treatment of periodontitis. Currently, controlled local drug delivery approach is more favorable as compared to systemic approach because it mainly focuses on improving the therapeutic outcomes by achieving factors like site-specific delivery, low dose requirement, bypass of first-pass metabolism, reduction in gastrointestinal side effects and decrease in dosing frequency. Overall it provides a safe and effective mode of treatment, which enhances patient compliance. Complete eradication of the organisms from the sites was not achieved by using various surgical and mechanical treatments. So a number of polymer-based delivery systems like fibers, films, chips, strips, microparticles, nanoparticles and nanofibers made from a variety of natural and synthetic materials have been successfully tested to deliver a variety of drugs. These systems are biocompatible and biodegradable, completely fill the pockets, and have strong retention on the target site due to excellent mucoadhesion properties. The review summarizes various available and recently developing targeted delivery devices for the treatment of periodontitis.

  4. A mucoadhesive endoluminal wearable sensory system.

    PubMed

    Chan, Cecilia K W; Zheng, Yali; Siu, Elaine H L; Yu, Ruoxi; Leung, Billy H K; Zhang, R; Poon, C C Y

    2015-08-01

    Bio- or muco-adhesive anchoring is a challenge for the development of advanced gastrointestinal (GI) surgical instruments, endoluminal monitoring devices and drug delivery systems. In this paper, we present a polymeric bio-adhesive film embedded with an optical sensor that can potentially be used to detect gastrointestinal bleeding. Four different formulas of mucoadhesive polymers were synthesized based on various chemical components and concentration combinations, and they were further layered with miniature photoplethymographic (PPG) sensors. The adhesive ability of the proposed mucoadhesive-sensor module was tested by attaching it to the lumen of a porcine stomach and compared amongst the four formulas. pH testing was also implemented to simulate the performance of the film in gastric cavity. To demonstrate the signal quality of this module, we also tested on the skin of five healthy subjects for hours. The observed shear detachment force between mucoadhesive film and porcine stomach tissue of all four formulations ranged from 0.09 to 1.38 N, and the performance of mucoadhesive film in pH 7 and pH 2 were similar. The module can attach firmly onto the skin for 3-10 hours with comparable PPG signal quality to traditional clip-based setup. With the advent of mucosal tissue anchoring by means of bioadhensive film, a wider extent of endoluminal procedures may become feasible. This emerging technology can also help shape the future of in-body wearable devices in the GI tract or other endoluminal cavities.

  5. Protein and Peptide Drug Delivery: Oral Approaches

    PubMed Central

    Shaji, Jessy; Patole, V.

    2008-01-01

    Till recent, injections remained the most common means for administering therapeutic proteins and peptides because of their poor oral bioavailability. However, oral route would be preferred to any other route because of its high levels of patient acceptance and long term compliance, which increases the therapeutic value of the drug. Designing and formulating a polypeptide drug delivery through the gastro intestinal tract has been a persistent challenge because of their unfavorable physicochemical properties, which includes enzymatic degradation, poor membrane permeability and large molecular size. The main challenge is to improve the oral bioavailability from less than 1% to at least 30-50%. Consequently, efforts have intensified over the past few decades, where every oral dosage form used for the conventional small molecule drugs has been used to explore oral protein and peptide delivery. Various strategies currently under investigation include chemical modification, formulation vehicles and use of enzyme inhibitors, absorption enhancers and mucoadhesive polymers. This review summarizes different pharmaceutical approaches which overcome various physiological barriers that help to improve oral bioavailability that ultimately achieve formulation goals for oral delivery. PMID:20046732

  6. Microfabrication for Drug Delivery

    PubMed Central

    Koch, Brendan; Rubino, Ilaria; Quan, Fu-Shi; Yoo, Bongyoung; Choi, Hyo-Jick

    2016-01-01

    This review is devoted to discussing the application of microfabrication technologies to target challenges encountered in life processes by the development of drug delivery systems. Recently, microfabrication has been largely applied to solve health and pharmaceutical science issues. In particular, fabrication methods along with compatible materials have been successfully designed to produce multifunctional, highly effective drug delivery systems. Microfabrication offers unique tools that can tackle problems in this field, such as ease of mass production with high quality control and low cost, complexity of architecture design and a broad range of materials. Presented is an overview of silicon- and polymer-based fabrication methods that are key in the production of microfabricated drug delivery systems. Moreover, the efforts focused on studying the biocompatibility of materials used in microfabrication are analyzed. Finally, this review discusses representative ways microfabrication has been employed to develop systems delivering drugs through the transdermal and oral route, and to improve drug eluting implants. Additionally, microfabricated vaccine delivery systems are presented due to the great impact they can have in obtaining a cold chain-free vaccine, with long-term stability. Microfabrication will continue to offer new, alternative solutions for the development of smart, advanced drug delivery systems. PMID:28773770

  7. Metrology for drug delivery.

    PubMed

    Lucas, Peter; Klein, Stephan

    2015-08-01

    In various recently published studies, it is argued that there are underestimated risks with infusion technology, i.e., adverse incidents believed to be caused by inadequate administration of the drugs. This is particularly the case for applications involving very low-flow rates, i.e., <1 ml/h and applications involving drug delivery by means of multiple pumps. The risks in infusing are caused by a lack of awareness, incompletely understood properties of the complete drug delivery system and a lack of a proper metrological infrastructure for low-flow rates. Technical challenges such as these were the reason a European research project "Metrology for Drug Delivery" was started in 2011. In this special issue of Biomedical Engineering, the results of that project are discussed.

  8. Lyophilized wafers comprising carrageenan and pluronic acid for buccal drug delivery using model soluble and insoluble drugs.

    PubMed

    Kianfar, Farnoosh; Antonijevic, Milan; Chowdhry, Babur; Boateng, Joshua S

    2013-03-01

    Lyophilized muco-adhesive wafers with optimum drug loading for potential buccal delivery have been developed. A freeze-annealing cycle was used to obtain optimized wafers from aqueous gels containing 2% κ-carrageenan (CAR 911), 4% pluronic acid (F127), 4.4% (w/w) polyethylene glycol with 1.8% (w/w) paracetamol or 0.8% (w/w) ibuprofen. Thermogravimetric analysis showed acceptable water content between 0.9 and 1.5%. Differential scanning calorimetry and X-ray diffraction showed amorphous conversion for both drugs. Texture analysis showed ideal mechanical and mucoadhesion characteristics whilst both drugs remained stable over 6 months and drug dissolution at a salivary pH showed gradual release within 2h. The results show the potential of CAR 911 and F127 based wafers for buccal mucosa drug delivery.

  9. Liposomes for drug delivery to the lungs by nebulization.

    PubMed

    Zaru, Marco; Mourtas, Spyridon; Klepetsanis, Pavlos; Fadda, Anna Maria; Antimisiaris, Sophia G

    2007-11-01

    Preparation of drug-loaded freeze-dried (FD) liposomes, designed for delivery to lungs after rehydration/nebulization was investigated. Rifampicin (RIF) incorporating multilamelar (MLV) and dried rehydrated vesicles (DRV); composed of phosphatidylcholine (PC), dipalmitoyloglycero-PC (DPPC) or distearoyloglycero-PC (DSPC), containing or not Cholesterol (Chol), were prepared. Vesicles were characterized for encapsulation efficiency (EE%), size distribution, zeta-potential, stability during freeze drying (FD) and nebulization (nebulization efficiency (NE%) and retention of RIF after nebulization (NER%)). Mucoadhesion and toxicity in A549 cells was measured. RIF EE% was not affected by liposome type but lipid composition was important; Synthetic lipid vesicles (DPPC and DSPC) had higher EE% compared to PC. As Chol increased EE% decreased. Freeze drying (FD) had no effect on EE%, however trehalose decreased EE% possibly due to RIF displacement. NER% was highly affected by lipid composition. Results of NE% and NER% for RIF-loaded liposomes show that DSPC/Chol (2:1) is the best composition for RIF delivery in vesicular form to lungs, by nebulization. Mucoadhesion and A549 cell toxicity studies were in line with this conclusion, however if mucoadhesion is required, improvement may be needed.

  10. Development and characterization of mucoadhesive buccal patches of salbutamol sulphate.

    PubMed

    Patel, Rajesh Singh; Poddar, S S

    2009-01-01

    Mucoadhesive patch releasing the drug in the oral cavity at predetermined rate may present distinct advantages over traditional dosage forms such as tablets, gels and solutions. The present study was concerned with the preparation and evaluation of mucoadhesive buccal patches for the controlled systemic delivery of Salbutamol sulphate to avoid first pass hepatic metabolism. The developed patches were evaluated for the physicochemical, mechanical and drug release characteristics. The patches showed desired mechanical and physicochemical properties to withstand environment of oral cavity. The in-vitro release study showed that patches could deliver drug to the oral mucosa for a period of 7 h. the patches exhibited adequate stability when tested under accelerated conditions.

  11. Single compartment drug delivery

    PubMed Central

    Cima, Michael J.; Lee, Heejin; Daniel, Karen; Tanenbaum, Laura M.; Mantzavinou, Aikaterini; Spencer, Kevin C.; Ong, Qunya; Sy, Jay C.; Santini, John; Schoellhammer, Carl M.; Blankschtein, Daniel; Langer, Robert S.

    2014-01-01

    Drug design is built on the concept that key molecular targets of disease are isolated in the diseased tissue. Systemic drug administration would be sufficient for targeting in such a case. It is, however, common for enzymes or receptors that are integral to disease to be structurally similar or identical to those that play important biological roles in normal tissues of the body. Additionally, systemic administration may not lead to local drug concentrations high enough to yield disease modification because of rapid systemic metabolism or lack of sufficient partitioning into the diseased tissue compartment. This review focuses on drug delivery methods that physically target drugs to individual compartments of the body. Compartments such as the bladder, peritoneum, brain, eye and skin are often sites of disease and can sometimes be viewed as “privileged,” since they intrinsically hinder partitioning of systemically administered agents. These compartments have become the focus of a wide array of procedures and devices for direct administration of drugs. We discuss the rationale behind single compartment drug delivery for each of these compartments, and give an overview of examples at different development stages, from the lab bench to phase III clinical trials to clinical practice. We approach single compartment drug delivery from both a translational and a technological perspective. PMID:24798478

  12. Chitosomes as drug delivery systems for C-phycocyanin: preparation and characterization.

    PubMed

    Manconi, M; Mura, S; Manca, M L; Fadda, A M; Dolz, M; Hernandez, M J; Casanovas, A; Díez-Sales, O

    2010-06-15

    The aim of this work was to investigate chitosomes, i.e. liposomes coated by a polyelectrolyte complex between chitosan (CH) and xantan gum (XG), as potential delivery system for oral administration of the protein C-phycocyanin. To this purpose several CH-XG-microcomplexes were prepared in aqueous lactic acid at different chitosan-xanthan gum percent ratios and rheological properties of the microcomplexes were studied to analyse the contribution of chitosan and xanthan gum in the reaction of microcomplexation. After establishing the best microcomplexes, chitosomes were prepared by coating C-phycocyanin loaded liposomes with the CH-XG hydrogels using spray-drying or freeze-drying. The chitosomes were characterized in terms of morphology, size distribution, zeta potential, swelling properties, drug release, and mucoadhesive properties. Rheological studies showed the influence of xanthan gum in the microcomplex properties. Moreover, obtained results demonstrated the effects of formulation and process variables on particle size, drug content, swelling, drug release, and especially on the mucoadhesiveness of C-PC chitosomes of CH-XG. In particular, chitosomes prepared by spray-drying technique using CH-XG in 0.5/8.0 (w/w) ratio showed a regular surface and a drug release characteristic for a Fickian diffusion of the active ingredient. The in vitro mucoadhesive study revealed that the spray-drying method is advantageous to prepare C-phycocyanin loaded chitosomes with excellent mucoadhesive properties for colonic drug delivery.

  13. Polymeric Micelles, a Promising Drug Delivery System to Enhance Bioavailability of Poorly Water-Soluble Drugs

    PubMed Central

    Ling, Peixue; Zhang, Tianmin

    2013-01-01

    Oral administration is the most commonly used and readily accepted form of drug delivery; however, it is find that many drugs are difficult to attain enough bioavailability when administered via this route. Polymeric micelles (PMs) can overcome some limitations of the oral delivery acting as carriers able to enhance drug absorption, by providing (1) protection of the loaded drug from the harsh environment of the GI tract, (2) release of the drug in a controlled manner at target sites, (3) prolongation of the residence time in the gut by mucoadhesion, and (4) inhibition of efflux pumps to improve the drug accumulation. To explain the mechanisms for enhancement of oral bioavailability, we discussed the special stability of PMs, the controlled release properties of pH-sensitive PMs, the prolongation of residence time with mucoadhesive PMs, and the P-gp inhibitors commonly used in PMs, respectively. The primary purpose of this paper is to illustrate the potential of PMs for delivery of poorly water-soluble drugs with bioavailability being well maintained. PMID:23936656

  14. New developments and opportunities in oral mucosal drug delivery for local and systemic disease.

    PubMed

    Hearnden, Vanessa; Sankar, Vidya; Hull, Katrusha; Juras, Danica Vidović; Greenberg, Martin; Kerr, A Ross; Lockhart, Peter B; Patton, Lauren L; Porter, Stephen; Thornhill, Martin H

    2012-01-01

    The oral mucosa's accessibility, excellent blood supply, by-pass of hepatic first-pass metabolism, rapid repair and permeability profile make it an attractive site for local and systemic drug delivery. Technological advances in mucoadhesives, sustained drug release, permeability enhancers and drug delivery vectors are increasing the efficient delivery of drugs to treat oral and systemic diseases. When treating oral diseases, these advances result in enhanced therapeutic efficacy, reduced drug wastage and the prospect of using biological agents such as genes, peptides and antibodies. These technologies are also increasing the repertoire of drugs that can be delivered across the oral mucosa to treat systemic diseases. Trans-mucosal delivery is now a favoured route for non-parenteral administration of emergency drugs and agents where a rapid onset of action is required. Furthermore, advances in drug delivery technology are bringing forward the likelihood of transmucosal systemic delivery of biological agents.

  15. Impact of chitosan composites and chitosan nanoparticle composites on various drug delivery systems: A review.

    PubMed

    Elgadir, M Abd; Uddin, Md Salim; Ferdosh, Sahena; Adam, Aishah; Chowdhury, Ahmed Jalal Khan; Sarker, Md Zaidul Islam

    2015-12-01

    Chitosan is a promising biopolymer for drug delivery systems. Because of its beneficial properties, chitosan is widely used in biomedical and pharmaceutical fields. In this review, we summarize the physicochemical and drug delivery properties of chitosan, selected studies on utilization of chitosan and chitosan-based nanoparticle composites in various drug delivery systems, and selected studies on the application of chitosan films in both drug delivery and wound healing. Chitosan is considered the most important polysaccharide for various drug delivery purposes because of its cationic character and primary amino groups, which are responsible for its many properties such as mucoadhesion, controlled drug release, transfection, in situ gelation, and efflux pump inhibitory properties and permeation enhancement. This review can enhance our understanding of drug delivery systems particularly in cases where chitosan drug-loaded nanoparticles are applied. Copyright © 2014. Published by Elsevier B.V.

  16. Development and characterization of surface modified PLGA nanoparticles for nasal vaccine delivery: effect of mucoadhesive coating on antigen uptake and immune adjuvant activity.

    PubMed

    Pawar, Dilip; Mangal, Sharad; Goswami, Roshan; Jaganathan, K S

    2013-11-01

    In this study, the efficacy of mucoadhesive polymers, i.e., chitosan and glycol chitosan as a mucoadhesive coating material in nasal vaccine delivery was investigated. The Hepatitis B surface Antigen (HBsAg) encapsulated PLGA, chitosan coated PLGA (C-PLGA), and Glycol chitosan coated PLGA (GC-PLGA) nanoparticles (NPs) were prepared. The formulations were characterized for particle size, shape, surface charge, and entrapment efficiency. The mucoadhesive ability of coated and non-coated NPs was determined using in vitro mucoadhesion and nasal clearance test. In addition, the systemic uptake and bio-distribution were also evaluated to understand the fate of NPs following nasal delivery. The immuno-adjuvant ability of various formulations was compared by measuring specific antibody titer in serum and secretory. The results indicated that PLGA NPs exhibit negative surface charge, whereas C-PLGA and GC-PLGA NPs exhibited positive surface charge. The GC-PLGA NPs demonstrated lower clearance and better local and systemic uptake compared to chitosan coated and uncoated PLGA NPs. In vivo immunogenicity studies indicated that GC-PLGA NPs could induce significantly higher systemic and mucosal immune response compared to PLGA and C-PLGA NPs. In conclusion, GC-PLGA NPs could be a promising carrier adjuvant for the nasal vaccine delivery for inducing a potent immune response at mucosal surface(s) and systemic circulation.

  17. Fabrication of a multifunctional nano-in-micro drug delivery platform by microfluidic templated encapsulation of porous silicon in polymer matrix.

    PubMed

    Zhang, Hongbo; Liu, Dongfei; Shahbazi, Mohammad-Ali; Mäkilä, Ermei; Herranz-Blanco, Bárbara; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

    2014-07-09

    A multifunctional nano-in-micro drug delivery platform is developed by conjugating the porous silicon nanoparticles with mucoadhesive polymers and subsequent encapsulation into a pH-responsive polymer using microfluidics. The multistage platform shows monodisperse size distribution and pH-responsive payload release, and the released nanoparticles are mucoadhesive. Moreover, this platform is capable of simultaneously loading and releasing multidrugs with distinct properties. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Gastroretentive mucoadhesive tablet of lafutidine for controlled release and enhanced bioavailability.

    PubMed

    Patil, Satish; Talele, Gokul S

    2015-05-01

    Lafutidine a newly developed histamine H2-receptor antagonist having biological half-life of 1.92 ± 0.94 h due to its selective absorption from upper part of gastrointestinal tract the development of mucoadhesive sustained release drug delivery system is recommended in order to enhance the bioavailability. A mucoadhesive tablets was developed using the natural polymer, sodium alginate, xanthan gum and karaya gum. Mucoadhesion is a complex phenomenon which involves wetting, adsorption and interpenetration of polymer chains. The prepared tablets of various formulations were evaluated for a total mucoadhesion time, buoyancy lag time and percentage drug released. The formulation with xanthan gum showed better results. Thus, it may be useful for prolonged drug release in stomach to improve the bioavailability and reduced dosing frequency. Non-fickians release transport was confirmed as the drug release mechanism from the optimized formulation by Korsmeyer-Peppas. The optimized formulation (B3) showed a mucoadhesive strength >35 g. In vivo study was performed using rabbits by X-ray imaging technique. Radiological evidences suggest that, a formulated tablet was well adhered for >10 h in rabbit's stomach. Optimized lafutidine mucoadhesive tablets showed no significant change in physical appearance, drug content, mucoadhesive properties and in vitro dissolution pattern after storage at 40 °C temperature 75 ± 5% relative humidity for 3 months.

  19. Transmucosal delivery of testosterone in rabbits using novel bi-layer mucoadhesive wax-film composite disks.

    PubMed

    Jay, Steven; Fountain, William; Cui, Zhengrong; Mumper, Russell J

    2002-09-01

    Testosterone exhibits very low oral bioavailability because of its low aqueous solubility and extensive first-pass metabolism. The purpose of this study was to develop a novel bi-layer mucoadhesive wax-film composite (WFC), and to test the relative bioavailability of testosterone via the buccal route in rabbits. The release rate of testosterone from optimal WFCs (3/8-in. diameter) per unit surface area was 5.6 microg x cm(2) x mL(-1) x min(-1) and was zero-order. Bi-layer WFCs (average weight of 14 +/- 2.6 mg and thickness of 186 +/- 34 microns) containing 4 mg of testosterone were applied to the buccal pouch of anesthetized New Zealand white rabbits. Rabbits (n = 3) injected intravenously had C(max) and area under the curve values of 1200 +/- 46 ng/mL, and 48,227 +/- 12,995 ng x min/mL, respectively. Rabbits (n = 3) dosed via the buccal pouch had C(max), T(max), and area under the curve values of 127 +/- 13 ng/mL, 200 +/- 35 min, and 24,221 +/- 1543 ng x min/mL. The relative bioavailability for rabbits treated with the WFC was 50.2 +/- 3.2% with a coefficient of variation of 6.4%. It was concluded that these bi-layer mucoadhesive WFCs disks could deliver physiologically relevant amounts of insoluble drugs such as testosterone across the buccal mucosa.

  20. Photomechanical drug delivery

    NASA Astrophysics Data System (ADS)

    Doukas, Apostolos G.; Lee, Shun

    2000-05-01

    Photomechanical waves (PW) are generated by Q-switched or mode-locked lasers. Ablation is a reliable method for generating PWs with consistent characteristics. Depending on the laser wavelength and target material, PWs with different parameters can be generated which allows the investigation of PWs with cells and tissue. PWs have been shown to permeabilize the stratum corneum (SC) in vivo and facilitate the transport of drugs into the skin. Once a drug has diffused into the dermis it can enter the vasculature, thus producing a systemic effect. Fluorescence microscopy of biopsies show that 40-kDa molecules can be delivered to a depth of > 300 micrometers into the viable skin of rats. Many important drugs such as insulin, and erythropoietin are smaller or comparable in size, making the PWs attractive for transdermal drug delivery. There are three possible pathways through the SC: Transappendageal via hair follicles or other appendages, transcellular through the corneocytes, and intercellular via the extracellular matrix. The intracellular route appears to be the most likely pathway of drug delivery through the SC.

  1. Microwave grafted, composite and coprocessed materials: drug delivery applications.

    PubMed

    Kaur, Loveleen; Singh, Inderbir

    2016-12-01

    Novel modified pharmaceutical materials with desired functionalities are required for the development of drug delivery systems. Excipients are no more inert ingredients but these are playing crucial roles in modifying physicochemical properties of drugs and for imparting desired functionalities in the delivery system. In this review article, modified materials such as grafted, composite and coprocessed have been discussed along with the updated reported literature on the same. Applications of grafted materials as drug release retardant, mucoadhesive polymer and tablet superdisintegrant have been elaborated. Use of composite materials in the development of transdermal films, hydrogels, microspheres, beads and nanoparticles have been discussed. Methods for the preparation of coprocessed materials along with commercial products of different coprocessed excipients have also been enlisted.

  2. Development of mucoadhesive sprayable gellan gum fluid gels.

    PubMed

    Mahdi, Mohammed H; Conway, Barbara R; Smith, Alan M

    2015-07-05

    The nasal mucosa provides a potentially good route for local and systemic drug delivery. However, the protective feature of the nasal cavity make intranasal delivery challenging. The application of mucoadhesive polymers in nasal drug delivery systems enhances the retention of the dosage form in the nasal cavity. Several groups have investigated using low acyl gellan as a drug delivery vehicle but only limited research however, has been performed on high acyl gellan for this purpose, despite its properties being more conducive to mucoadhesion. High acyl gellan produces highly elastic gels below 60°C which make it difficult to spray using a mechanical spray device. Therefore, in this study we have tried to address this problem by making fluid gels by introducing a shear force during gelation of the gellan polymer. These fluid gel systems contain gelled micro-particles suspended in a solution of un-gelled polymer. These systems can therefore behave as pourable viscoelastic fluids. In this study we have investigated the rheological behavior and mucoadhesion of fluid gels of two different types of gellan (high and low acyl) and fluid gels prepared from blends of high and low acyl gellan at a 50:50 ratio. The results demonstrated that by preparing fluid gels of high acyl gellan, the rheological properties were sufficient to spray through a standard nasal spray device. Moreover fluid gels also significantly enhance both high acyl and low acyl gellan mucoadhesion properties.

  3. Alginate-based hybrid aerogel microparticles for mucosal drug delivery.

    PubMed

    Gonçalves, V S S; Gurikov, P; Poejo, J; Matias, A A; Heinrich, S; Duarte, C M M; Smirnova, I

    2016-10-01

    The application of biopolymer aerogels as drug delivery systems (DDS) has gained increased interest during the last decade since these structures have large surface area and accessible pores allowing for high drug loadings. Being biocompatible, biodegradable and presenting low toxicity, polysaccharide-based aerogels are an attractive carrier to be applied in pharmaceutical industry. Moreover, some polysaccharides (e.g. alginate and chitosan) present mucoadhesive properties, an important feature for mucosal drug delivery. This feature allows to extend the contact of DDS with biological membranes, thereby increasing the absorption of drugs through the mucosa. Alginate-based hybrid aerogels in the form of microparticles (<50μm) were investigated in this work as carriers for mucosal administration of drugs. Low methoxyl pectin and κ-carrageenan were co-gelled with alginate and further dried with supercritical CO2 (sc-CO2). Spherical mesoporous aerogel microparticles were obtained for alginate, hybrid alginate/pectin and alginate/κ-carrageenan aerogels, presenting high specific surface area (370-548m(2)g(-1)) and mucoadhesive properties. The microparticles were loaded with ketoprofen via adsorption from its solution in sc-CO2, and with quercetin via supercritical anti-solvent precipitation. Loading of ketoprofen was in the range between 17 and 22wt% whereas quercetin demonstrated loadings of 3.1-5.4wt%. Both the drugs were present in amorphous state. Loading procedure allowed the preservation of antioxidant activity of quercetin. Release of both drugs from alginate/κ-carrageenan aerogel was slightly faster compared to alginate/pectin. The results indicate that alginate-based aerogel microparticles can be viewed as promising matrices for mucosal drug delivery applications.

  4. Evaluation of a mucoadhesive buccal patch for delivery of peptides: in vitro screening of bioadhesion.

    PubMed

    Li, C; Bhatt, P P; Johnston, T P

    1998-10-01

    We have assessed the bioadhesive properties of several different mucoadhesive buccal patches. The patches consisted of custom coformulations of silicone polymers and Carbopol 974P. The contact angle of water was measured for each of the test formulations, using an ophthalmic shadow scope. The corresponding work of adhesion between the water and the patches (W1), and between the patches and freshly-excised rabbit buccal mucosa (W2) was then calculated, using a modification of Dupre's equation. The bioadhesive strength between the patches and excised rabbit buccal mucosa was also assessed. The results of the contact-angle measurements indicated that the contact angle decreased with an increase in the amount of Carbopol in the formulation. Additionally, the calculated values of both W1 and W2 increased with an increase in the amount of Carbopol in the buccal-patch formulations. A correlation (r not equal to 0.9808) was found between the measured contact angle and the calculated values for W2. The direct measurement of the force required to separate a buccal patch from excised rabbit buccal mucosa with the INSTRON demonstrated that the adhesive strength increased with an increase in the amount of Carbopol. This preliminary study has shown that the measurement of contact angles alone may provide a useful technique for estimating the work of adhesion, and may serve as a convenient and rapid screening procedure to identify potential mucoadhesive buccal-patch formulations.

  5. Bioadhesive okra polymer based buccal patches as platform for controlled drug delivery.

    PubMed

    Kaur, Gurpreet; Singh, Deepinder; Brar, Vivekjot

    2014-09-01

    In the present investigation, polysaccharide from the Okra fruits (Hibiscus esculentus) was extracted, characterized and explored for its mucoadhesive potential. Mucoadhesive films of okra polymer (OP) were prepared by solvent casting method based on 3(2) factorial design. For these studies, OP (2.0%, 2.5%, 3.0%, w/v) and glycerol (plasticizer) (0.25%, 0.50%, 0.75%, v/v) were taken as independent variables while tensile strength, mucoadhesive strength, contact angle, swelling index and residence time as dependent variables. The developed films were evaluated for their physicochemical, mechanical and electrical properties. The formulated films were found to be smooth, flexible, and displayed adequate mucoadhesive and tensile strength. Their near neutral pH and negative hemolytic studies indicated their non-irritability and biocompatible nature with biological tissues. The formulation comprising of 3% OP and 0.5% glycerol (F8) was found to exhibit optimum mechanical properties. Further, optimized film was loaded with zolmitriptan (model drug) to determine its drug release profiles. In vitro and ex vivo drug release studies demonstrated a controlled release of zolmitriptan over a period of 8h in simulated salivary fluid (SSF) pH 6.8, with the correlation coefficient values indicating its non-Fickian kinetics. Thus, OP can be used as a promising biomaterial for controlled drug delivery.

  6. The basics and underlying mechanisms of mucoadhesion.

    PubMed

    Smart, John D

    2005-11-03

    Mucoadhesion is where two surfaces, one of which is a mucous membrane, adhere to each other. This has been of interest in the pharmaceutical sciences in order to enhance localised drug delivery, or to deliver 'difficult' molecules (proteins and oligonucleotides) into the systemic circulation. Mucoadhesive materials are hydrophilic macromolecules containing numerous hydrogen bond forming groups, the carbomers and chitosans being two well-known examples. The mechanism by which mucoadhesion takes place has been said to have two stages, the contact (wetting) stage followed by the consolidation stage (the establishment of the adhesive interactions). The relative importance of each stage will depend on the individual application. For example, adsorption is a key stage if the dosage form cannot be applied directly to the mucosa of interest, while consolidation is important if the formulation is exposed to significant dislodging stresses. Adhesive joint failure will inevitably occur as a result of overhydration of a dosage form, or as a result of epithelia or mucus turnover. New mucoadhesive materials with optimal adhesive properties are now being developed, and these should enhance the potential applications of this technology.

  7. Nanomaterials for Drugs Delivery

    SciTech Connect

    Márquez, Francisco; Morant, Carmen

    2014-07-01

    Nanotechnology has revolutionized engineering, biology, chemistry, physics and medicine of today. These disciplines are evolving thanks to the ongoing development of new materials and applications. Nanomedicine, as application of nanotechnology in the field of health care, has undergone unprecedented development. Some of these changes have real applications as, for example, the use of nanoparticles in MRI imaging, in hyperthermia, in immunotherapy, or to improve the bioavailability of drugs, among others. Furthermore, when a drug is administered to a patient, the blood distributes it throughout the body. In the case of very localized diseases (i.e. tumors), only a small fraction of the drug reaches the target. Chemotherapy is one of the most aggressive treatment options used in some types of cancer, and is usually administered intravenously. The drug circulates throughout the body, reaching and destroying healthy and cancerous tissues, producing side effects throughout the body, sometimes with serious consequences for the health of the patient (nephrotoxicity, cardiotoxicity, peripheral neuropathy, anemia, etc.) in this type of therapy. Among the many applications of nanotechnology, the fabrication of nanostructures capable of safely transporting these drugs is seen as a strategy for reducing these side effects. Nanoparticles are able to carry and release the drug in the right place and with the required dose, greatly reducing the problems associated with direct treatment with these drugs. In recent years, there have been continuous improvements in the design and development of new tailor-made drug delivery systems, including hollow magnetic nanoparticles, liposomal structures, dendrimers, nanoporous silicon, etc. These structures can be obtained with different molecular weights (in the case of polymers), structures, shapes, and even with the appropriate functional groups for interaction at the desired positions. But, a great effort is still required to solve many

  8. Nanomaterials for Drugs Delivery

    DOE PAGES

    Márquez, Francisco; Morant, Carmen

    2014-07-01

    Nanotechnology has revolutionized engineering, biology, chemistry, physics and medicine of today. These disciplines are evolving thanks to the ongoing development of new materials and applications. Nanomedicine, as application of nanotechnology in the field of health care, has undergone unprecedented development. Some of these changes have real applications as, for example, the use of nanoparticles in MRI imaging, in hyperthermia, in immunotherapy, or to improve the bioavailability of drugs, among others. Furthermore, when a drug is administered to a patient, the blood distributes it throughout the body. In the case of very localized diseases (i.e. tumors), only a small fraction ofmore » the drug reaches the target. Chemotherapy is one of the most aggressive treatment options used in some types of cancer, and is usually administered intravenously. The drug circulates throughout the body, reaching and destroying healthy and cancerous tissues, producing side effects throughout the body, sometimes with serious consequences for the health of the patient (nephrotoxicity, cardiotoxicity, peripheral neuropathy, anemia, etc.) in this type of therapy. Among the many applications of nanotechnology, the fabrication of nanostructures capable of safely transporting these drugs is seen as a strategy for reducing these side effects. Nanoparticles are able to carry and release the drug in the right place and with the required dose, greatly reducing the problems associated with direct treatment with these drugs. In recent years, there have been continuous improvements in the design and development of new tailor-made drug delivery systems, including hollow magnetic nanoparticles, liposomal structures, dendrimers, nanoporous silicon, etc. These structures can be obtained with different molecular weights (in the case of polymers), structures, shapes, and even with the appropriate functional groups for interaction at the desired positions. But, a great effort is still required to

  9. Comparative in vivo mucoadhesion studies of thiomer formulations using magnetic resonance imaging and fluorescence detection.

    PubMed

    Albrecht, K; Greindl, M; Kremser, C; Wolf, C; Debbage, P; Bernkop-Schnürch, A

    2006-09-28

    The aim of this study was to compare different oral delivery systems based on the thiolated polymer polycarbophil-cysteine (PCP-Cys) and to provide evidence for the validity of the hypothesis that unhydrated polymers provide better mucoadhesion in vivo. To achieve dry polymer application, a new, experimental dosage form named Eutex (made of Eudragit L100-55 and latex) capsule has been developed. Magnetic resonance imaging was used to localize the point of release of the thiolated polymer from the application forms via the positive magnetic resonance signal from a gadolinium complex (Gd-DTPA). In vivo mucoadhesion was determined by ascertaining the residence time of the fluorescence-tagged thiomer on intestinal mucosa after 3 h. Results showed that in comparison to conventional application forms the Eutex capsules led to 1.9-fold higher mucoadhesive properties of PCP-Cys when compared to application with a conventional enteric-coated capsule, and to 1.4-fold higher mucoadhesion when compared to administration with an enteric-coated tablet of the thiomer. The findings of this study should contribute to the understanding of mucoadhesion and mucoadhesion influencing parameters in vivo and should therefore be of considerable interest for the development of future mucoadhesive oral drug delivery dosage forms.

  10. Evaluation of Calendula mucilage as a mucoadhesive and controlled release component in buccal tablets

    PubMed Central

    Sabale, V.; Patel, V.; Paranjape, A.

    2014-01-01

    Mucoadhesive drug delivery systems were developed to sustain drug delivery via various mucus membranes for either local or systemic delivery of poorly absorbed drugs such as peptides and proteins as well as drugs that are subjected to high first-pass metabolism. The present study was undertaken to use isolated Calendula mucilage as a mucoadhesive agent and to formulate controlled release buccoadhesive tablets with an intention to avoid hepatic first-pass metabolism as well as to enhance residence time of drug in the buccal cavity. The mucilage was isolated from the Calendula petals by aqueous extraction method and characterized for various physiochemical parameters as well as for its adhesive properties. By using direct compression technique, tablets were prepared containing dried mucilage and chlorpheniramine maleate (CPM) as a model drug. Three batches of tablets were prepared and evaluated containing three mucoadhesive components namely Methocel K4M, Carbopol 974P and isolated Calendula mucilage in 16.66%, 33.33 % and 50 % (1:2:3 ratio) resulting in 9 different formulations. FTIR studies between mucilage and CPM suggested the absence of a chemical interaction between CPM and Calendula mucilage. The results of the study showed that the isolated mucilage had good physicochemical and morphological characteristics and tablets conformed to the pharmacopoeial specifications. Also in vitro release studies showed controlled action of drug with increasing the concentration of the isolated Calendula mucilage as a mucoadhesive agent in the formulations. Permeability studies indicated that permeability behavior was not statistically different (P>0.05) by changing the mucoadhesive component. The formulated mucoadhesive tablets for buccal administration containing 75 mg Calendula mucilage showed controlled drug release. Thus, mucoadhesive natural Calendula mucilage based buccal tablets for controlled release were successfully formulated. PMID:25598798

  11. Evaluation of Calendula mucilage as a mucoadhesive and controlled release component in buccal tablets.

    PubMed

    Sabale, V; Patel, V; Paranjape, A

    2014-01-01

    Mucoadhesive drug delivery systems were developed to sustain drug delivery via various mucus membranes for either local or systemic delivery of poorly absorbed drugs such as peptides and proteins as well as drugs that are subjected to high first-pass metabolism. The present study was undertaken to use isolated Calendula mucilage as a mucoadhesive agent and to formulate controlled release buccoadhesive tablets with an intention to avoid hepatic first-pass metabolism as well as to enhance residence time of drug in the buccal cavity. The mucilage was isolated from the Calendula petals by aqueous extraction method and characterized for various physiochemical parameters as well as for its adhesive properties. By using direct compression technique, tablets were prepared containing dried mucilage and chlorpheniramine maleate (CPM) as a model drug. Three batches of tablets were prepared and evaluated containing three mucoadhesive components namely Methocel K4M, Carbopol 974P and isolated Calendula mucilage in 16.66%, 33.33 % and 50 % (1:2:3 ratio) resulting in 9 different formulations. FTIR studies between mucilage and CPM suggested the absence of a chemical interaction between CPM and Calendula mucilage. The results of the study showed that the isolated mucilage had good physicochemical and morphological characteristics and tablets conformed to the pharmacopoeial specifications. Also in vitro release studies showed controlled action of drug with increasing the concentration of the isolated Calendula mucilage as a mucoadhesive agent in the formulations. Permeability studies indicated that permeability behavior was not statistically different (P>0.05) by changing the mucoadhesive component. The formulated mucoadhesive tablets for buccal administration containing 75 mg Calendula mucilage showed controlled drug release. Thus, mucoadhesive natural Calendula mucilage based buccal tablets for controlled release were successfully formulated.

  12. Polymers for Drug Delivery Systems

    PubMed Central

    Liechty, William B.; Kryscio, David R.; Slaughter, Brandon V.; Peppas, Nicholas A.

    2012-01-01

    Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery. PMID:22432577

  13. Designing mucoadhesive discs containing stem bark extract of Ziziphus jujuba based on Iranian traditional documents

    PubMed Central

    Hamedi, Shokouhsadat; Shams-Ardakani, Mohammad Reza; Sadeghpour, Omid; Amin, Gholamreza; Hajighasemali, Dawood; Orafai, Hossein

    2016-01-01

    Objective (s): Mucoadhesive disc is one of the various routes of drug delivery for curing buccal disease Materials and Methods: Every discs containing 70 mg stem bark extract of Ziziphus jujuba were formulated by using Carbopol 934, PVP k30 and gelatin as polymers. Discs were made by granulation and direct compression. Discs were standardized based on the total phenol. Properties such as in vitro and in vivo mucoadhesion, drug release, water uptake, and disintegration were carried out. Results: Discs showed excellent mucoadhesion and released high amount of the active ingredients (47%) immediately and completed after approximately the first hour. They had a good adhesion in buccal cavity. Conclusion: This study showed that the kinetics of release of the active substance from the mucoadhesive disc obeyed the zero order kinetic and didn’t follow the fick's law. The water uptake and dissolution (DS), increased with the passing of time. PMID:27114804

  14. Optimizing drugs for local delivery.

    PubMed

    Collingwood, S; Lock, R; Searcey, M

    2009-12-01

    An international panel of speakers together with approximately 70 delegates were brought together by The Society for Medicines Research's symposium on Optimising Drugs for Local Delivery, held on June 11, 2009 at the Novartis Institutes for Biomedical Research, Horsham, UK. The focus of the conference was on the delivery of drugs direct to the site of action and the consequences of this delivery route on delivery technologies, formulation science and molecular design.

  15. Microprocessor controlled transdermal drug delivery.

    PubMed

    Subramony, J Anand; Sharma, Ashutosh; Phipps, J B

    2006-07-06

    Transdermal drug delivery via iontophoresis is reviewed with special focus on the delivery of lidocaine for local anesthesia and fentanyl for patient controlled acute therapy such as postoperative pain. The role of the microprocessor controller in achieving dosimetry, alternating/reverse polarity, pre-programmed, and sensor-based delivery is highlighted. Unique features such as the use of tactile signaling, telemetry control, and pulsatile waveforms in iontophoretic drug delivery are described briefly.

  16. Controlled Drug Delivery Using Microdevices

    PubMed Central

    Sanjay, Sharma T.; Dou, Maowei; Fu, Guanglei; Xu, Feng; Li, XiuJun

    2016-01-01

    Therapeutic drugs administered systematically are evenly distributed to the whole body through blood circulation and have to cross many biological barriers before reaching the pathological site. Conventional drug delivery may make drugs inactive or reduce their potency as they may be hydrolyzed or degraded enzymatically and are rapidly excreted through the urinary system resulting in suboptimal concentration of drugs at the desired site. Controlled drug delivery aims to localize the pharmacological activity of the drug to the desired site at desired release rates. The advances made by micro/nanofluidic technologies have provided new opportunities for better-controlled drug delivery. Various components of a drug delivery system can be integrated within a single tiny micro/nanofluidic chip. This article reviews recent advances of controlled drug delivery made by microfluidic/nanofluidic technologies. We first discuss microreservoir-based drug delivery systems. Then we highlight different kinds of microneedles used for controlled drug delivery, followed with a brief discussion about the current limitations and the future prospects of controlled drug delivery systems. PMID:26813304

  17. Sonophoresis in transdermal drug deliverys.

    PubMed

    Park, Donghee; Park, Hyunjin; Seo, Jongbum; Lee, Seunghun

    2014-01-01

    Transdermal drug delivery (TDD) has several significant advantages compared to oral drug delivery, including elimination of pain and sustained drug release. However, the use of TDD is limited by low skin permeability due to the stratum corneum (SC), the outermost layer of the skin. Sonophoresis is a technique that temporarily increases skin permeability such that various medications can be delivered noninvasively. For the past several decades, various studies of sonophoresis in TDD have been performed focusing on parameter optimization, delivery mechanism, transport pathway, or delivery of several drug categories including hydrophilic and high molecular weight compounds. Based on these various studies, several possible mechanisms of sonophoresis have been suggested. For example, cavitation is believed to be the predominant mechanism responsible for drug delivery in sonophoresis. This review presents details of various studies on sonophoresis including the latest trends, delivery of various therapeutic drugs, sonophoresis pathways and mechanisms, and outlook of future studies.

  18. MRI in ocular drug delivery.

    PubMed

    Li, S Kevin; Lizak, Martin J; Jeong, Eun-Kee

    2008-11-01

    Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed.

  19. MRI in ocular drug delivery

    PubMed Central

    Li, S. Kevin; Lizak, Martin J.; Jeong, Eun-Kee

    2008-01-01

    Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. PMID:18186077

  20. Synthesis of thiolated chitosan and preparation nanoparticles with sodium alginate for ocular drug delivery

    PubMed Central

    Su, Meiqin; Tang, Shaoheng; Wang, Lingsong; Liang, Xinfang; Meng, Feihong; Hong, Ying; Xu, Zhiran

    2012-01-01

    Purpose The goal of the present study was to synthesize mucoadhesive polymer – thiolated chitosan (TCS) from chitosan (CS), then prepared CS/TCS-sodium alginate nanoparticles (CS/TCS-SA NPs), determined which was more potential for ocular drug delivery. Methods A new method for preparing TCS was developed, and the characteristics were determined using Fourier transform infrared spectroscopy and the degree of thiol immobilized was measured by Ellman’s reagent. Human corneal epithelium (HCE) cells were incubated with different concentrations of TCS for 48 h to determine the cell viabilities. CS/TCS-SA NPs were prepared and optimized by a modified ionic gelation method. The particle sizes, zeta potentials, Scanning electron microscopy images, mucoadhesion, in vitro cell uptake and in vivo studies of the two types of NP were compared. Results The new method enabled a high degree of thiol substitution of TCS, up to 1,411.01±4.02 μmol/g. In vitro cytocompatibility results suggest that TCS is nontoxic. Compared to CS-SA NPs, TCS-SA NPs were more stable, with higher mucoadhesive properties and could deliver greater amounts of drugs into HCE cells in vitro and cornea in vivo. Conclusions TCS-SA NPs have better delivery capability, suggesting they have good potential for ocular drug delivery applications. PMID:22876124

  1. Hollow Pollen Shells to Enhance Drug Delivery

    PubMed Central

    Diego-Taboada, Alberto; Beckett, Stephen T.; Atkin, Stephen L.; Mackenzie, Grahame

    2014-01-01

    Pollen grain and spore shells are natural microcapsules designed to protect the genetic material of the plant from external damage. The shell is made up of two layers, the inner layer (intine), made largely of cellulose, and the outer layer (exine), composed mainly of sporopollenin. The relative proportion of each varies according to the plant species. The structure of sporopollenin has not been fully characterised but different studies suggest the presence of conjugated phenols, which provide antioxidant properties to the microcapsule and UV (ultraviolet) protection to the material inside it. These microcapsule shells have many advantageous properties, such as homogeneity in size, resilience to both alkalis and acids, and the ability to withstand temperatures up to 250 °C. These hollow microcapsules have the ability to encapsulate and release actives in a controlled manner. Their mucoadhesion to intestinal tissues may contribute to the extended contact of the sporopollenin with the intestinal mucosa leading to an increased efficiency of delivery of nutraceuticals and drugs. The hollow microcapsules can be filled with a solution of the active or active in a liquid form by simply mixing both together, and in some cases operating a vacuum. The active payload can be released in the human body depending on pressure on the microcapsule, solubility and/or pH factors. Active release can be controlled by adding a coating on the shell, or co-encapsulation with the active inside the shell. PMID:24638098

  2. Release of triamcinolone acetonide from mucoadhesive polymer composed of chitosan and poly(acrylic acid) in vitro.

    PubMed

    Ahn, Jae-Soon; Choi, Hoo-Kyun; Chun, Myong-Kwan; Ryu, Jei-Man; Jung, Jae-Hee; Kim, Yue-Un; Cho, Chong-Su

    2002-03-01

    Transmucosal drug delivery (TMD) system using mucoadhesive polymer has been recently interested due to the rapid onset of action, high blood level, avoidance of the first-pass effect and the exposure of the drug to the gastrointestinal tract. A novel mucoadhesive polymer complex composed of chitosan and poly(acrylic acid) (PAA) was prepared by template polymerization of acrylic acid in the presence of chitosan for the TMD system. Triamcinolone acetonide (TAA) was loaded into the chitosan/PAA polymer complex film. TAA was evenly dispersed in chitosan, PAA polymer complex film without interaction with polymer complex. Release behavior of TAA from the mucoadhesive polymer film was dependent on time, pH, loading content of drug, and chitosan PAA ratio. The analysis of the drug release from the mucoadhesive film showed that TAA might be released from the chitosan/PAA polymer complex film through non-Fickian diffusion mechanism.

  3. Brain targeted delivery of mucoadhesive thermosensitive nasal gel of selegiline hydrochloride for treatment of Parkinson's disease.

    PubMed

    Sridhar, Vinay; Wairkar, Sarika; Gaud, Ram; Bajaj, Amrita; Meshram, Pramod

    2017-07-18

    Selegiline hydrochloride (SL), is an anti-Parkinson's agent, has low-oral bioavailability due to its high first pass metabolism and scarce oral absorption. In the present study, SL mucoadhesive nasal thermosensitive gel (SNT-gel) was prepared to enhance the bioavailability and subsequently, its concentration in the brain. The SNT-gel was prepared using Poloxamer 407-Chitosan combination and optimised formulation was further evaluated for physicochemical parameters. The comparative pharmacodynamic studies including behavioural studies, biochemical testing and histopathology of the brain was carried out in rats for SNT-gel, SL-nasal solution and SL Marketed Tablets. The optimised SNT-gel formulation (SNT-V) revealed sol-gel transition at 33-34°C. In-vitro diffusion study of SNT-V showed 102.37 ± 2.1% diffusion at 12 h which reduced to 89.64 ± 1.2% in Ex-vivo diffusion. Comparative results of behavioural studies indicated an improved score of photoactometer and reduced motor deficit (catalepsy score) in SNT-gel treatment group as compared with other groups. Similarly, a significant increase in brain dopamine, reduction in monoamine oxidase B level, increase in catalase activity and level of reduced glutathione upon treatment with SNT-gel indicated its effectiveness which was also supported by histopathology results. Therefore, nasal thermosensitive gel holds better potential for brain targeting in Parkinson's disease over the conventional nasal or oral formulations.

  4. Cell-Mediated Drugs Delivery

    PubMed Central

    Batrakova, Elena V.; Gendelman, Howard E.; Kabanov, Alexander V.

    2011-01-01

    INTRODUCTION Drug targeting to sites of tissue injury, tumor or infection with limited toxicity is the goal for successful pharmaceutics. Immunocytes (including mononuclear phagocytes (dendritic cells, monocytes and macrophages), neutrophils, and lymphocytes) are highly mobile; they can migrate across impermeable barriers and release their drug cargo at sites of infection or tissue injury. Thus immune cells can be exploited as trojan horses for drug delivery. AREAS COVERED IN THIS REVIEW This paper reviews how immunocytes laden with drugs can cross the blood brain or blood tumor barriers, to facilitate treatments for infectious diseases, injury, cancer, or inflammatory diseases. The promises and perils of cell-mediated drug delivery are reviewed, with examples of how immunocytes can be harnessed to improve therapeutic end points. EXPERT OPINION Using cells as delivery vehicles enables targeted drug transport, and prolonged circulation times, along with reductions in cell and tissue toxicities. Such systems for drug carriage and targeted release represent a novel disease combating strategy being applied to a spectrum of human disorders. The design of nanocarriers for cell-mediated drug delivery may differ from those used for conventional drug delivery systems; nevertheless, engaging different defense mechanisms into drug delivery may open new perspectives for the active delivery of drugs. PMID:21348773

  5. Biocompatibility of Chitosan Carriers with Application in Drug Delivery

    PubMed Central

    Rodrigues, Susana; Dionísio, Marita; Remuñán López, Carmen; Grenha, Ana

    2012-01-01

    Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures. PMID:24955636

  6. Ultrasound mediated transdermal drug delivery.

    PubMed

    Azagury, Aharon; Khoury, Luai; Enden, Giora; Kost, Joseph

    2014-06-01

    Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injections. However, the stratum corneum serves as a barrier that limits the penetration of substances to the skin. Application of ultrasound (US) irradiation to the skin increases its permeability (sonophoresis) and enables the delivery of various substances into and through the skin. This review presents the main findings in the field of sonophoresis in transdermal drug delivery as well as transdermal monitoring and the mathematical models associated with this field. Particular attention is paid to the proposed enhancement mechanisms and future trends in the fields of cutaneous vaccination and gene therapy.

  7. Synthesis of mucoadhesive thiolated gelatin using a two-step reaction process.

    PubMed

    Duggan, Sarah; O'Donovan, Orla; Owens, Eleanor; Cummins, Wayne; Hughes, Helen

    2015-04-01

    Using a novel two-step approach, the thiolation of gelatin for mucoadhesive drug delivery has been achieved. The initial step involved the amination of native gelatin via an amine to carboxylic acid coupling reaction with ethylene diamine, followed by thiolation with Traut's reagent. The resulting thiolated product showed an increase in thiol content of up to 10-fold in comparison with control gelatin samples. Improved cohesion and mucoadhesion in comparison with unmodified and control gelatin samples was also observed. This reaction process was observed to be influenced by both the temperature and the pH of the amination reaction, affecting both amine content and product yield. Swelling ability, cohesion and mucoadhesion were all observed to be strongly dependent on the thiol content of the samples but also, importantly, the molecular weight (MW) of the gelatin used. Gelatin with a MW of 20-25 kDa proved to be optimal in creating this novel mucoadhesive gelatin material.

  8. Why Chitosan? From properties to perspective of mucosal drug delivery.

    PubMed

    Kumar, Ashwini; Vimal, Archana; Kumar, Awanish

    2016-10-01

    Non-parenteral drug delivery routes primarily remove the local pain at the injection site. The drugs administered through the oral route encounter the process of hepatic first pass metabolism. Among the alternative delivery routes, mucosal route is being investigated as the most preferred route. Different mucosal routes include the gastrointestinal tract (oral), vagina, buccal cavity and nasal cavity. Novel formulations are being developed using natural and synthetic polymers that could increase the residence time of the drug at mucosal surface in order to facilitate permeation and reduce (or bypass) the first pass metabolism. For recombinant drugs, the formulations are accompanied by enzyme inhibitors and penetration enhancers. Buccal cavity (buccal and sublingual mucosa) has smaller surface area than the gastrointestinal tract but the drugs can easily escape the first pass metabolism. Chitosan is the most applied natural polymer while synthetic polymers include Carbopol and Eudragit. Chitosan has inherent properties of mucoadhesion and penetration enhancement apart from biodegradability and efflux pump inhibition. This review hoards the important research purview of chitosan as a compatible drug carrier macromolecule for mucosal delivery on single platform.

  9. Development and gamma-scintigraphy study of Hibiscus rosasinensis polysaccharide-based microspheres for nasal drug delivery.

    PubMed

    Sharma, Nitin; Tyagi, Shanu; Gupta, Satish Kumar; Kulkarni, Giriraj Thirupathirao; Bhatnagar, Aseem; Kumar, Neeraj

    2016-11-01

    This work describes the application of natural plant polysaccharide as pharmaceutical mucoadhesive excipients in delivery systems to reduce the clearance rate through nasal cavity. Novel natural polysaccharide (Hibiscus rosasinensis)-based mucoadhesive microspheres were prepared by using emulsion crosslinking method for the delivery of rizatriptan benzoate (RB) through nasal route. Mucoadhesive microspheres were characterized for different parameters and nasal clearance of technetium-99m ((99m)Tc)-radiolabeled microspheres was determined by using gamma-scintigraphy. Their Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) studies showed that the drug was stable during preparation of microspheres. Aerodynamic diameter of microspheres was in the range 13.23 ± 1.83-33.57 ± 3.69 µm. Change in drug and polysaccharide ratio influenced the mucoadhesion, encapsulation efficiency and in-vitro release property. Scintigraphs taken at regular interval indicate that control solution was cleared rapidly from nasal cavity, whereas microspheres showed slower clearance (p < 0.005) with half-life of 160 min. Natural polysaccharide-based microspheres achieved extended residence by minimizing effect of mucociliary clearance with opportunity of sustained delivery for longer duration.

  10. A gastroretentive drug delivery system of lisinopril imbibed on isabgol-husk.

    PubMed

    Semwal, Ravindra; Semwal, Ruchi Badoni; Semwal, Deepak Kumar

    2014-01-01

    The gastroretentive drug delivery system is site-specific and allows the drug to remain in the stomach for a prolonged period of time so that it can be released in a controlled manner in gastrointestinal tract. The present study was carried out to develop a gastroretentive drug delivery system using isabgol as an excipient to prolong the residence time of the model drug lisinopril in the stomach. The gastroretentive ability of isabgol was increased by addition of NaHCO3 as a gas-generating agent while its mucoadhesive property was enhanced by incorporation of HPMC-K4M. The drug, NaHCO3 and HPMC-K3M were imbibed on isabgol-husk as per entrapment efficiency of the isabgol-husk. After drying, the product was filled in a hard gelatin capsule and evaluated for its buoyancy, mucoadhesive properties, swelling index and in vitro drug release. The lisinopril released through isabgol was delayed by 12 hours when compared to a preparation available on the market which released the complete drug in 0.5 hours. The drug release study of lisinopril from the formulation follows first order kinetics using a diffusion controlled mechanism. The results from the present study revealed that isabgol can be used as a potential excipient for the formulation of gastroretentive drug delivery systems in the near future.

  11. Drug delivery to the ear.

    PubMed

    Hoskison, E; Daniel, M; Al-Zahid, S; Shakesheff, K M; Bayston, R; Birchall, J P

    2013-01-01

    Drug delivery to the ear is used to treat conditions of the middle and inner ear such as acute and chronic otitis media, Ménière's disease, sensorineural hearing loss and tinnitus. Drugs used include antibiotics, antifungals, steroids, local anesthetics and neuroprotective agents. A literature review was conducted searching Medline (1966-2012), Embase (1988-2012), the Cochrane Library and Ovid (1966-2012), using search terms 'drug delivery', 'middle ear', 'inner ear' and 'transtympanic'. There are numerous methods of drug delivery to the middle ear, which can be categorized as topical, systemic (intravenous), transtympanic and via the Eustachian tube. Localized treatments to the ear have the advantages of targeted drug delivery allowing higher therapeutic doses and minimizing systemic side effects. The ideal scenario would be a carrier system that could cross the intact tympanic membrane loaded with drugs or biochemical agents for the treatment of middle and inner ear conditions.

  12. Mucoadhesive in situ gel formulation for vaginal delivery of clotrimazole: formulation, preparation, and in vitro/in vivo evaluation.

    PubMed

    Rençber, Seda; Karavana, Sinem Yaprak; Şenyiğit, Zeynep Ay; Eraç, Bayri; Limoncu, Mine Hoşgör; Baloğlu, Esra

    2017-06-01

    The purpose of this study was to develop a suitable mucoadhesive in situ gel formulation of clotrimazole (CLO) for the treatment of vaginal candidiasis. For this aim, the mixture of poloxamer (PLX) 407 and 188 were used to prepare in situ gels. Hydroxypropyl methylcellulose (HPMC) K100M or E50 was added to in situ gels in 0.5% ratio to improve the mucoadhesive and mechanical properties of formulations and to prolong the residence time in vaginal cavity. After the preparation of mucoadhesive in situ gels; gelation temperature/time, viscosity, mechanical, mucoadhesive, syringeability, spreadibility and rheological properties, in vitro release behavior, and anticandidal activities were determined. Moreover vaginal retention of mucoadhesive in situ gels was investigated with in vivo distribution studies in rats. Based on the obtained results, it was found that gels prepared with 20% PLX 407, 10% PLX 188 and 0.5% HPMC K100M/E50 might be suitable for vaginal administration of CLO. In addition, the results of in vivo distribution studies showed that gel formulations remained on the vaginal mucosa even 24 h after application. In conclusion, the mucoadhesive in situ gels of CLO would be alternative candidate for treatment of vaginal candidiasis since it has suitable gel properties with good vaginal retention.

  13. Drug release and washability of mucoadhesive gels based on sodium carboxymethylcellulose and polyacrylic acid.

    PubMed

    Rossi, S; Bonferoni, M C; Ferrari, F; Caramella, C

    1999-01-01

    This study investigated the relationship of the washability of gels based on two mucoadhesive polymers (sodium carboxymethylcellulose [NaCMC] and polyacrylic acid [PAA]) and their mixtures to their physical properties such as consistency and hydration/dissolution. The mucoadhesive properties of the two polymers and the effect of mucus-polymer interaction on gel washability at the mucoadhesive interface were also investigated using mixtures of PAA and NaCMC gels with increasing mucin amounts. Release and wash-away properties of the gels were assessed by means of a simultaneous release and wash-away test, whereas the consistency and hydration/dissolution properties of the gels were investigated by rheological analysis (viscosity and dynamic viscoelastic tests) and liquid uptake measurements, respectively. The results showed that PAA was characterized by lower release and wash-away properties than those of NaCMC. Mixing of two gels at different ratios allowed modulation of the release and wash-away properties. A relationship between washability and hydration/dissolution properties was found. Gel consistency by itself did not always provide a complete explanation of the wash-away process. The two polymers investigated showed different rheological interaction properties with mucin. Depending on the extent of such interaction, gel-mucin mixture had hydration/dissolution and washability properties that were quite different with respect to the initial gel.

  14. Intranasal delivery of antipsychotic drugs.

    PubMed

    Katare, Yogesh K; Piazza, Justin E; Bhandari, Jayant; Daya, Ritesh P; Akilan, Kosalan; Simpson, Madeline J; Hoare, Todd; Mishra, Ram K

    2016-11-29

    Antipsychotic drugs are used to treat psychotic disorders that afflict millions globally and cause tremendous emotional, economic and healthcare burdens. However, the potential of intranasal delivery to improve brain-specific targeting remains unrealized. In this article, we review the mechanisms and methods used for brain targeting via the intranasal (IN) route as well as the potential advantages of improving this type of delivery. We extensively review experimental studies relevant to intranasal delivery of therapeutic agents for the treatment of psychosis and mental illnesses. We also review clinical studies in which intranasal delivery of peptides, like oxytocin (7 studies) and desmopressin (1), were used as an adjuvant to antipsychotic treatment with promising results. Experimental animal studies (17) investigating intranasal delivery of mainstream antipsychotic drugs have revealed successful targeting to the brain as suggested by pharmacokinetic parameters and behavioral effects. To improve delivery to the brain, nanotechnology-based carriers like nanoparticles and nanoemulsions have been used in several studies. However, human studies assessing intranasal delivery of mainstream antipsychotic drugs are lacking, and the potential toxicity of nanoformulations used in animal studies has not been explored. A brief discussion of future directions anticipates that if limitations of low aqueous solubility of antipsychotic drugs can be overcome and non-toxic formulations used, IN delivery (particularly targeting specific tissues within the brain) will gain more importance moving forward given the inherent benefits of IN delivery in comparison to other methods.

  15. Nanoencapsulation for drug delivery

    PubMed Central

    Kumari, Avnesh; Singla, Rubbel; Guliani, Anika; Yadav, Sudesh Kumar

    2014-01-01

    Nanoencapsulation of drug/small molecules in nanocarriers (NCs) is a very promising approach for development of nanomedicine. Modern drug encapsulation methods allow efficient loading of drug molecules inside the NCs thereby reducing systemic toxicity associated with drugs. Targeting of NCs can enhance the accumulation of nanonencapsulated drug at the diseased site. This article focussed on the synthesis methods, drug loading, drug release mechanism and cellular response of nanoencapsulated drugs on liposomes, micelles, carbon nanotubes, dendrimers, and magnetic NCs. Also the uses of these various NCs have been highlighted in the field of nanotechnology. PMID:26417260

  16. Cellulose nanofiber aerogel as a promising biomaterial for customized oral drug delivery.

    PubMed

    Bhandari, Jyoti; Mishra, Harshita; Mishra, Pawan Kumar; Wimmer, Rupert; Ahmad, Farhan J; Talegaonkar, Sushama

    2017-01-01

    Cellulose nanofiber (CNF) aerogels with favorable floatability and mucoadhesive properties prepared by the freeze-drying method have been introduced as new possible carriers for oral controlled drug delivery system. Bendamustine hydrochloride is considered as the model drug. Drug loading was carried out by the physical adsorption method, and optimization of drug-loaded formulation was done using central composite design. A very lightweight-aerogel-with-matrix system was produced with drug loading of 18.98%±1.57%. The produced aerogel was characterized for morphology, tensile strength, swelling tendency in media with different pH values, floating behavior, mucoadhesive detachment force and drug release profiles under different pH conditions. The results showed that the type of matrix was porous and woven with excellent mechanical properties. The drug release was assessed by dialysis, which was fitted with suitable mathematical models. Approximately 69.205%±2.5% of the drug was released in 24 hours in medium of pH 1.2, whereas ~78%±2.28% of drug was released in medium of pH 7.4, with floating behavior for ~7.5 hours. The results of in vivo study showed a 3.25-fold increase in bioavailability. Thus, we concluded that CNF aerogels offer a great possibility for a gastroretentive drug delivery system with improved bioavailability.

  17. Cellulose nanofiber aerogel as a promising biomaterial for customized oral drug delivery

    PubMed Central

    Bhandari, Jyoti; Mishra, Harshita; Mishra, Pawan Kumar; Wimmer, Rupert; Ahmad, Farhan J; Talegaonkar, Sushama

    2017-01-01

    Cellulose nanofiber (CNF) aerogels with favorable floatability and mucoadhesive properties prepared by the freeze-drying method have been introduced as new possible carriers for oral controlled drug delivery system. Bendamustine hydrochloride is considered as the model drug. Drug loading was carried out by the physical adsorption method, and optimization of drug-loaded formulation was done using central composite design. A very lightweight-aerogel-with-matrix system was produced with drug loading of 18.98%±1.57%. The produced aerogel was characterized for morphology, tensile strength, swelling tendency in media with different pH values, floating behavior, mucoadhesive detachment force and drug release profiles under different pH conditions. The results showed that the type of matrix was porous and woven with excellent mechanical properties. The drug release was assessed by dialysis, which was fitted with suitable mathematical models. Approximately 69.205%±2.5% of the drug was released in 24 hours in medium of pH 1.2, whereas ~78%±2.28% of drug was released in medium of pH 7.4, with floating behavior for ~7.5 hours. The results of in vivo study showed a 3.25-fold increase in bioavailability. Thus, we concluded that CNF aerogels offer a great possibility for a gastroretentive drug delivery system with improved bioavailability. PMID:28352172

  18. Drug Delivery Systems for Platinum Drugs

    NASA Astrophysics Data System (ADS)

    Huynh, Vien T.; Scarano, Wei; Stenzel, Martina H.

    2013-09-01

    Since the discovery of cisplatin, drugs based on platinum, have made a significant impact on the treatment of various cancers. The administration of platinum drugs is however accompanied by significant side effects. This chapter discusses the types of drug delivery systems that have been developed in order to enable the targeted delivery while maintaining controlled temporal supply of the drug. The sizes of carriers range from nanometer to micrometer sized particles. The most common types of drug carriers are micelles, liposomes, nanoparticles, and dendrimers, but also a few microspheres have been developed. Most striking aspect of the delivery of platinum drugs is the possibility of physical encapsulation but also the binding of the drug to the polymer carrier coordinate covalent bond. Since platinum drugs have typically two permanent and two leaving ligands, the polymer can be part of either ligand. As the leaving ligand, the platinum drug is released often as cisplatin. If the polymer provides the functionality for the permanent ligand, a new macromolecular drug has been formed. In addition to the attachment of pt(II) drugs, recent offorts are devoted to the conjugation via the Pt((IV) prodrug.

  19. Photoresponsive nanoparticles for drug delivery

    PubMed Central

    Rwei, Alina Y.; Wang, Weiping; Kohane, Daniel S.

    2015-01-01

    Summary Externally triggerable drug delivery systems provide a strategy for the delivery of therapeutic agents preferentially to a target site, presenting the ability to enhance therapeutic efficacy while reducing side effects. Light is a versatile and easily tuned external stimulus that can provide spatiotemporal control. Here we will review the use of nanoparticles in which light triggers drug release or induces particle binding to tissues (phototargeting). PMID:26644797

  20. Formulation and evaluation of nano based drug delivery system for the buccal delivery of acyclovir.

    PubMed

    Al-Dhubiab, Bandar E; Nair, Anroop B; Kumria, Rachna; Attimarad, Mahesh; Harsha, Sree

    2015-12-01

    Oral bioavailability of acyclovir is limited, primarily because of low permeability across the gastrointestinal membrane. The purpose of this study is the prospective evaluation of buccal films impregnated with acyclovir loaded nanospheres as a drug delivery system to improve systemic bioavailability. Acyclovir polymeric nanospheres were prepared by double emulsion solvent evaporation technique. Nanospheres were embedded into buccoadhesive films (A1-A4) comprising of different concentrations of polymers (Eudragit RL 100, HPMC K15 and carbopol 974P). Films were characterized for physico-mechanical properties, mucoadhesive strength, hydration, drug release and ex vivo permeation. In vivo studies were carried out on rabbits to assess the pharmacokinetic profile of buccal film (A3) as compared to oral therapy. The prepared films demonstrated excellent physical properties, adequate hydration and buccoadhesive strength. In vitro drug release data inferred that the drug release was dependent on the composition of film. Ex vivo permeation studies indicated greater flux in film A3. In vivo studies revealed a significant enhancement in absorption of acyclovir (P<0.0001) with Cmax (~3 folds) and AUC0-α (~8 folds, P<0.0001) when compared to oral dosing. Moreover, the extended Tmax value (6h) signifies the potential of the prepared film to prolong acyclovir delivery. Given the promising results, the study concludes that the developed buccal film (A3) impregnated with acyclovir loaded nanospheres could be a promising approach for effective delivery of acyclovir.

  1. Phototriggered multifunctional drug delivery device

    NASA Astrophysics Data System (ADS)

    Härtner, S.; Kim, H.-C.; Hampp, N.

    2006-02-01

    Although phototriggered cleavage of chemical bonds induced by single-photon or two-photon-absorption provides attractive tools for controlled drug delivery, the choice of drugs is still limited by the linker system to which the therapeutic molecules need to be bound covalently. The use of a multifunctional linker system suitable for coupling a broad spectrum of drugs to the polymeric carrier will open a new field for drug delivery. We have developed a novel photocleavable multifunctional linker system based on coumarin dimers, whose unique photochemical behavior are well characterized. As a first example, an acrylic polymer-drug conjugate with antimetabolites is explored. The cleavage of the link between the drug and the polymer backbone is triggered by both single- as well as two-photon absorption. The release of the drug is investigated. It is possible to manufacture a polymeric drug delivery device with several drugs in different areas. In particular the two-photon-absorption induced process offers the possibility to address the drug of interest owing to the superior spatial resolution. The key to such devices is a versatile linker-system which can be adopted to work with various drug compounds.

  2. Mucoadhesive bilayered tablets for buccal sustained release of flurbiprofen.

    PubMed

    Perioli, Luana; Ambrogi, Valeria; Giovagnoli, Stefano; Ricci, Maurizio; Blasi, Paolo; Rossi, Carlo

    2007-07-13

    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.

  3. Design, formulation, and physicochemical evaluation of periodontal propolis mucoadhesive gel

    PubMed Central

    Aslani, Abolfazl; Malekpour, Negar

    2016-01-01

    Background: Periodontitis is a disease of tooth supporting tissues, and Gram-negative Bacteria are the main cause of this. Propolis has antibacterial, anti-inflammatory, and antioxidant effects due to its high polyphenol and flavonoids content. The aim of this study is the formulation of a mucoadhesive gel containing concentrated extract of propolis for treatment of periodontitis. Materials and Methods: Formulations containing carbopol 940, sodium carboxymethylcellulose (NaCMC), hydroxypropyl methylcellulose K4M, and propolis extract were prepared. Among ten prepared formulations, five formulations had acceptable and proper physical appearance and uniformity; thus, they were selected for physicochemical tests (centrifugal, thermal change, cooling and heating, freeze and thaw, thermal stress, and pH evaluation), quantification of flavonoids, viscosity, mucoadhesion, drug release, and syringeability tests. We investigated the antibacterial activity of F10 (carbopol 940 1%, NaCMC 3%) against Porphyromonas gingivalis using the disk diffusion method. Results: Phenolic content was measured 39.02 ± 3.24 mg/g of concentrated extract as gallic acid and flavonoid content was determined 743.28 ± 12.1 mg/g of concentrated extract as quercetin. Highest viscosity (3700 cps) and mucoadhesion (21 MPa) were seen in F10. Study of release profile in F10 also revealed that propolis could release from this system in more than 7 days. All of the five selected formulations had ease of syringeability in 21-gauge needle for drug delivery into periodontal pocket. In the disk diffusion method, F10 produced significant growth inhibition zones against P. gingivalis. Conclusion: Controlled release of drug into periodontal pocket helps effective treatment and recovery, higher persistence and reduces drug use frequency. Increase of carbopol 940 leads to viscosity and mucoadhesion elevation and accordingly decreases of release rate. F10 was the best formulation because of highest viscosity and

  4. In vitro evaluation of some parameters involved in mucoadhesion of aqueous polymeric dispersions.

    PubMed

    Burgalassi, Susi; Monti, Daniela; Tampucci, Silvia; Chetoni, Patrizia

    2014-07-25

    Abstract Context: The mucoadhesive formulations are constantly developing due to their relevance in the drug delivery to various districts of the organism. Objective: The purpose of this study was to find a direct link between physicochemical properties of the polymers and their adhesive ability in order to offer guidelines for the development of mucoadhesive semisolid formulations. Materials and methods: Twelve polymers were dispersed in water and characterized with regard to their mucoadhesiveness, apparent viscosity, contact angle on solid surface, and hydrodynamic diameter of their molecules. The adhesive properties were related to the other measured parameters. Results and discussion: The data seem to indicate the existence of an optimal value of viscosity, around 5-6 Pa s, to obtain the highest mucoadhesiveness of the polymeric dispersions. Regarding the molecular sizes, the best mucoadhesive performances seem to be given from polymers with a hydrodynamic diameter lower than 350-400 nm. In any case, the ability to wet the surface by the polymeric dispersion seems to play an essential role in bioadhesion process, capable of strongly limiting the phenomenon. Conclusions: Performing simple in vitro measurements, it seems possible to identify the best polymeric concentration to obtain a semisolid formulation with good mucoadhesive properties.

  5. Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery

    NASA Astrophysics Data System (ADS)

    Ensign-Hodges, Laura

    A method that could provide more uniform and longer-lasting drug delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections and inflammatory bowel disease. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. Here, we investigate the use of muco-inert mucus-penetrating nanoparticles (MPP) for improving vaginal and gastrointestinal drug delivery. Conventional hydrophobic nanoparticles strongly adhere to mucus, facilitating rapid clearance from the body. Here, we demonstrate that mucoadhesive polystyrene nanoparticles (conventional nanoparticles, CP) become mucus-penetrating in human cervicovaginal mucus (CVM) after pretreatment with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large MPP did not change in F127 pretreated CVM, implying there is no affect on the native pore structure of CVM. Additionally, there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for one week. Importantly, HSV virus remains adherent in F127-pretreated CVM. Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that hypotonically-induced fluid uptake could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We evaluated hypotonic formulations for delivering water-soluble drugs and for drug delivery with MPP. Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that isotonic formulations

  6. Calcium alginate-carboxymethyl cellulose beads for colon-targeted drug delivery.

    PubMed

    Agarwal, Tarun; Narayana, S N Gautham Hari; Pal, Kunal; Pramanik, Krishna; Giri, Supratim; Banerjee, Indranil

    2015-04-01

    The present study delineates preparation, characterization and application of calcium alginate (CA)-carboxymethyl cellulose (CMC) beads for colon-specific oral drug delivery. Here, we exploited pH responsive swelling, mucoadhesivity and colonic microflora-catered biodegradability of the formulations for colon-specific drug delivery. The CA-CMC beads were prepared by ionic gelation method and its physicochemical characterization was done by SEM, XRD, EDAX, DSC and texture analyzer. The swelling and mucoadhesivity of the beads was found higher at the simulated colonic environment. Variation was more prominent in compositions with lower CMC concentrations. CA-CMC formulations degraded slowly in simulated colonic fluid, however the degradation rate increased drastically in the presence of colonic microflora. In vitro release study of anticancer drug 5-fluorouracil (5-FU) showed a release (>90%) in the presence of colonic enzymes. A critical analysis of drug release profile along with FRAP (fluorescence recovery after photobleaching) study revealed that the presence of CMC in the formulation retarded the release rate of 5-FU. 5-FU-loaded formulations were tested against colon adenocarcinoma cells (HT-29). Cytotoxicity data, nuclear condensation-fragmentation and apoptosis analysis (by flow cytometry) together confirmed the therapeutic potential of the CA-CMC formulations. In conclusion, CA-CMC beads can be used for colon-specific drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Thiolation of arabinoxylan and its application in the fabrication of controlled release mucoadhesive oral films.

    PubMed

    Hanif, Muhammad; Zaman, Muhammad

    2017-03-20

    Mucoadhesion is an important property that helps oral drug delivery system to remain attached with buccal mucosa and hence to improve the delivery of the drug. The current study was designed to achieve the thiol modification of Arabinoxylan (ARX) and to develop a mucoadhesive oral film for the improved delivery of tizanidine hydrochloride (TZN HCl). Synthesis of thiolated arabinoxylan (TARX) was accomplished by esterification of ARX with thioglycolic acid (TGA). TARX was further used for the development of mucoadhesive oral films which were prepared by using a solvent casting technique. Formulation of the films was designed and optimized by using central composite design (CCRD), selecting TARX (X1) and glycerol (X2) as variables. Prepared film formulations were evaluated for mechanical strength, ex-vivo mucoadhesion, in-vitro drug release, ex-vivo drug permeation, surface morphology and drug contents. Thiolation of ARX was confirmed by fourier transform infra-red spectroscopy (FTIR) as a peak related to thiol group appeared at 2516 cm(-1). The claim of successful thiolation of ARX was strengthened by the presence of 2809.003 ± 1.03 μmoles of thiol contents per gram of the polymer, which was determined by Ellman's reagent method. From the results, it was observed that the films were of satisfactory mechanical strength and mucoadhesiveness with folding endurance greater than 300 and mucoadhesive strength 11.53 ± 0.17 N, respectively. Reasonable drug retention was observed during in-vitro dissolution (85.03% cumulative drug release) and ex-vivo permeation (78.90% cumulative amount of permeated drug) studies conducted for 8 h. Effects of varying concentrations of both polymer and plasticizer on prepared mucoadhesive oral films were evaluated by ANOVA and it was observed that glycerol can enhanced the dissolution as well as permeation of the drug while TARX has opposite impact on these parameters. In nutshell, TARX in combination with glycerolwas found to

  8. Absorption-improving effects of chitosan oligomers based on their mucoadhesive properties: a comparative study on the oral and pulmonary delivery of calcitonin.

    PubMed

    Zhang, Hailong; Huang, Xiaoyan; Sun, Ya; Xing, Jianfeng; Yamamoto, Akira; Gao, Yang

    2016-09-01

    Effects of chitosan oligomers with different types and varying concentrations on the intestinal and pulmonary absorptions of calcitonin were investigated in rats by an in situ closed loop method and an in vivo pulmonary absorption experiment, respectively. Various chitosan oligomers demonstrated different efficiencies in improving the intestinal and pulmonary absorptions of calcitonin, and chitosan hexamer with the optimal concentration of 0.5% (w/v) showed the greatest absorption enhancing effect. Moreover, pharmacodynamic parameters of calcitonin after its coadministration intrapulmonarily with various chitosan oligomers were consistently larger than that in the intestinal delivery, indicating the superior potential of pulmonary administration for systemic delivery of calcitonin. Furthermore, various chitosan oligomers neither obviously increased release amounts of protein nor activities of lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF), revealing the safety of these chitosan oligomers to lung tissue. In addition, bioadhesions of various chitosan oligomers were well consistent with their absorption enhancing effects in the absorption experiment, suggesting the contribution of mucoadhesive properties of chitosan oligomers to their absorption improving effects. Taken together, chitosan oligomers, especially chitosan hexamer, can effectively improve the intestinal and pulmonary absorptions of calcitonin partly due to the mucoadhesion between positive chitosan oligomers and negative mucus in the membrane.

  9. Rheological Analysis of Polymer Interactions and Ageing of Poly(Methylvinylether-Co-Maleic Anhydride)/Poly(Vinyl Alcohol) Binary Networks and Their Effects on Mucoadhesion.

    PubMed

    Andrews, Gavin P; Laverty, Thomas P; Jones, David S

    2015-12-01

    Polymer blends of poly(vinylalcohol, PVA) and poly(methylvinylether-co-maleic anhydride, PMVE/MA) were formulated and their viscoelastic and mucoadhesive properties characterised. The viscoelastic and mucoadhesive properties were dependent on polymer concentration, molecular weight of PVA and PVA:PMVE/MA ratio. Alteration of these properties allowed platforms to be designed to offer defined rheological and mucoadhesive properties, properties that could not be achieved using monopolymeric platforms. A strong correlation was noted between the modulus of the polymeric blends and mucoadhesion. After storage, the polymeric blends underwent rheological structuring (ageing) with an attendant enhancement of mucoadhesion. In certain blends containing the highest molecular weight of PVA (146-186 kDa), storage ultimately resulted in an increase and then a significant decrease in the rheological and mucoadhesive properties, the latter phenomenon being accredited to polymer recrystallisation. Ageing of the rheological and mucoadhesive properties was modelled using an exponential growth model, allowing predictions of the storage period associated with the maxima in viscoelastic and mucoadhesive properties. These observations highlight the possible implications whenever interactive polymeric blends are employed in drug delivery. Caution is therefore urged whenever a formulation strategy based on interactive polymer blends is employed to ensure that ageing is fully understood and mathematically characterised.

  10. Albumin nanoparticles carrying cyclodextrins for nasal delivery of the anti-Alzheimer drug tacrine.

    PubMed

    Luppi, Barbara; Bigucci, Federica; Corace, Giuseppe; Delucca, Alice; Cerchiara, Teresa; Sorrenti, Milena; Catenacci, Laura; Di Pietra, Anna Maria; Zecchi, Vittorio

    2011-11-20

    Peroral administration of tacrine, the first acetylcholinestearse inhibitor licensed for the treatment of Alzheimer's disease, is associated with low bioavailability, due to an extended first-pass methabolism, short elimination half-life and hepatotoxicity. Nasal drug delivery may reduce the degree of these problems. Tacrine hydrochloride nasal delivery is here investigated by means of albumin nanoparticles carrying beta cyclodextrin and two different beta cyclodextrin derivatives (hydroxypropyl beta cyclodextrin and sulphobutylether beta cyclodextrin). Bovine serum albumin nanoparticles were obtained using a coacervation method, followed by thermal cross-linking, starting from protein solution at alkaline pH. After preparation, nanoparticles were loaded by soaking from solutions of tacrine hydrochloride and lyophilised. Thermal analysis (differential scanning calorimetry and thermogravimetric analysis) supported by Fourier Transform Infrared Spectroscopy were performed in order to confirm protein cross-linking in nanosphere structure and possible drug/carrier interaction occurred after the loading process. Moreover, size, polydispersity, zeta potential and morphology of the nanoparticles were investigated as well as drug loading, mucoadhesion properties and ex-vivo drug permeation ability. Results indicate that all the nanoparticles presented a mean size and a polydispersity lower than 300nm and 0.33nm, respectively, were spherical shaped and negatively charged even after drug loading. Moreover, the presence of the different beta cyclodextrins in the polymeric network affected drug loading and could differently modulate nanoparticle mucoadhesiveness and drug permeation behaviour. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Mathematical modeling of drug delivery.

    PubMed

    Siepmann, J; Siepmann, F

    2008-12-08

    Due to the significant advances in information technology mathematical modeling of drug delivery is a field of steadily increasing academic and industrial importance with an enormous future potential. The in silico optimization of novel drug delivery systems can be expected to significantly increase in accuracy and easiness of application. Analogous to other scientific disciplines, computer simulations are likely to become an integral part of future research and development in pharmaceutical technology. Mathematical programs can be expected to be routinely used to help optimizing the design of novel dosage forms. Good estimates for the required composition, geometry, dimensions and preparation procedure of various types of delivery systems will be available, taking into account the desired administration route, drug dose and release profile. Thus, the number of required experimental studies during product development can be significantly reduced, saving time and reducing costs. In addition, the quantitative analysis of the physical, chemical and potentially biological phenomena, which are involved in the control of drug release, offers another fundamental advantage: The underlying drug release mechanisms can be elucidated, which is not only of academic interest, but a pre-requisite for an efficient improvement of the safety of the pharmaco-treatments and for effective trouble-shooting during production. This article gives an overview on the current state of the art of mathematical modeling of drug delivery, including empirical/semi-empirical and mechanistic realistic models. Analytical as well as numerical solutions are described and various practical examples are given. One of the major challenges to be addressed in the future is the combination of mechanistic theories describing drug release out of the delivery systems with mathematical models quantifying the subsequent drug transport within the human body in a realistic way. Ideally, the effects of the design

  12. Enema ion compositions for enhancing colorectal drug delivery.

    PubMed

    Maisel, Katharina; Chattopadhyay, Sumon; Moench, Thomas; Hendrix, Craig; Cone, Richard; Ensign, Laura M; Hanes, Justin

    2015-07-10

    Delivering drugs to the colorectum by enema has advantages for treating or preventing both local and systemic diseases. However, the properties of the enema itself are not typically exploited for improving drug delivery. Sodium ions are actively pumped out of the lumen of the colon, which is followed by osmotically-driven water absorption, so we hypothesized that this natural mechanism could be exploited to drive nanoparticles and drugs to the colorectal tissue surface. Here, we report that sodium-based, absorption-inducing (hypotonic) enemas rapidly transport hydrophilic drugs and non-mucoadhesive, mucus penetrating nanoparticles (MPP), deep into the colorectal folds to reach virtually the entire colorectal epithelial surface. In contrast, isotonic and secretion-inducing (hypertonic) vehicles led to non-uniform, poor surface coverage. Sodium-based enemas induced rapid fluid absorption even when moderately hyper-osmolal (~350 mOsm) compared to blood (~300 mOsm), which suggests that active sodium absorption plays a key role in osmosis-driven fluid uptake. We then used tenofovir, an antiretroviral drug in clinical trials for preventing HIV, to test the effects of enema composition on local and systemic drug delivery. We found that strongly hypotonic and hypertonic enemas caused rapid systemic drug uptake, whereas moderately hypotonic enemas with ion compositions similar to feces resulted in high local tissue levels with minimal systemic drug exposure. Similarly, moderately hypotonic enemas provided improved local drug retention in colorectal tissue, whereas hypertonic and isotonic enemas provided markedly reduced drug retention in colorectal tissue. Lastly, we found that moderately hypotonic enema formulations caused little to no detectable epithelial damage, while hypertonic solutions caused significant damage, including epithelial sloughing; the epithelial damage caused increased systemic drug absorption and penetration of MPP into colorectal tissue, a potential

  13. Development and optimisation of mucoadhesive nanoparticles of acyclovir using design of experiments approach.

    PubMed

    Kharia, Ankit Anand; Singhai, Akhlesh Kumar

    2015-01-01

    The aim of our study was to improve the bioavailability of acyclovir (ACV) by delivery of mucoadhesive nanoparticles (NPs) and controlled delivery of drug at its absorption window. Central composite design was used by which the effects of independent variables (gelatin and Pluronic F-68) on various responses such as particle size, polydispersity index, entrapment efficiency, loading efficiency, drug release and mucoadhesive strength were studied. The optimised formulation was evaluated for morphology, stability, pharmacokinetic and gastrointestinal tracking. The optimised NPs were found to be nearly spherical. Changes in characteristics of NPs were not significant after six months of accelerated stability studies. In vivo mucoadhesion study showed significant retention of mucoadhesive NPs in upper gastro-intestinal tract for more than 12 h. Pharmacokinetic study in rats revealed that mucoadhesive NPs could maintain relatively steady plasma concentration of ACV for more than 10 h. The AUC0-∞ and mean residence time of optimised formulation (7527.9 ng h/mL and 12.09 h) were significantly high than tablet dispersion (3841.13 ng h/mL and 7.97 h).

  14. Development of Imiquimod-Loaded Mucoadhesive Films for Oral Dysplasia

    PubMed Central

    Ramineni, S.K.; Cunningham, L.L.; Dziubla, T.D.; Puleo, D.A.

    2013-01-01

    Oral squamous dysplasia, which can usually be readily visualized as leukoplakia during an oral examination and confirmed by histology, is often considered a premalignant condition. Current treatments, however, focus on the final stages of disease, and treatments such as surgery can lead to postoperative disabilities. Hence, this study was designed to develop a noninvasive, mucoadhesive drug delivery system loaded with an immune response modifier, imiquimod, as treatment for precancerous dysplastic lesions. Blends of polyvinylpyrrolidone and carboxymethylcellulose were used to prepare mucoadhesive films that were backed with poly(ethylene-co-vinyl acetate). Because of the hydrophobic nature of imiquimod, four methods of loading (sonication, linoleic acid, 2-hydroxypropyl-β-cyclodextrin, and acetate buffer) were compared. The formation of imiquimod-cyclodextrin complexes and their solubility was studied by differential scanning calorimetry and phase solubility studies. All films achieved sustained release of drug for three hours except for those prepared by linoleic acid. The high solubility of imiquimod in acetate buffer facilitated high loading capability and greater release (68%) of drug than did the other formulations (approximately 40%). In summary, a noninvasive and local approach with the potential to treat precancerous lesions may be achieved by this described mucoadhesive drug delivery system. PMID:23192692

  15. Tamarind seed polysaccharide-gellan mucoadhesive beads for controlled release of metformin HCl.

    PubMed

    Nayak, Amit Kumar; Pal, Dilipkumar; Santra, Kousik

    2014-03-15

    The paper describes the development, optimization and evaluation of tamarind seed polysaccharide (TSP)-blended gellan gum (GG) mucoadhesive beads containing metformin HCl through Ca(2+)-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 ± 0.24 mm.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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Chitosan in nasal delivery systems for therapeutic drugs.

    PubMed

    Casettari, Luca; Illum, Lisbeth

    2014-09-28

    There is an obvious need for efficient and safe nasal absorption enhancers for the development of therapeutically efficacious nasal products for small hydrophilic drugs, peptides, proteins, nucleic acids and polysaccharides, which do not easily cross mucosal membranes, including the nasal. Recent years have seen the development of a range of nasal absorption enhancer systems such as CriticalSorb (based on Solutol HS15) (Critical Pharmaceuticals Ltd), Chisys based on chitosan (Archimedes Pharma Ltd) and Intravail based on alkylsaccharides (Aegis Therapeutics Inc.), that is presently being tested in clinical trials for a range of drugs. So far, none of these absorption enhancers have been used in a marketed nasal product. The present review discusses the evaluation of chitosan and chitosan derivatives as nasal absorption enhancers, for a range of drugs and in a range of formulations such as solutions, gels and nanoparticles and finds that chitosan and its derivatives are able to efficiently improve the nasal bioavailability. The revirtew also questions whether chitosan nanoparticles for systemic drug delivery provide any real improvement over simpler chitosan formulations. Furthermore, the review also evaluates the use of chitosan formulations for the improvement of transport of drugs directly from the nasal cavity to the brain, based on its mucoadhesive characteristics and its ability to open tight junctions in the olfactory and respiratory epithelia. It is found that the use of chitosan nanoparticles greatly increases the transport of drugs from nose to brain over and above the effect of simpler chitosan formulations.

  17. Drug release from xyloglucan beads coated with Eudragit for oral drug delivery.

    PubMed

    Yoo, Mi Kyong; Choi, Hoo Kyun; Kim, Tae Hee; Choi, Yun Jaie; Akaike, Toshihiro; Shirakawa, Mayumi; Cho, Chong Su

    2005-06-01

    Xyloglucan (XG), which exhibits thermal sol to gel transition, non-toxicity, and low gelation concentration, is of interest in the development of sustained release carriers for drug delivery. Drug-loaded XG beads were prepared by extruding dropwise a dispersion of indomethacin in aqueous XG solution (2 wt.-%) through a syringe into corn oil. Enteric coating of XG bead was performed using Eudragit L 100 to improve the stability of XG bead in gastrointestinal (GI) track and to achieve gastroresistant drug release. Release behavior of indomethacin from XG beads in vitro was investigated as a function of loading content of drug, pH of release medium, and concentration of coating agent. Adhesive force of XG was also measured using the tensile test. Uniform-sized spherical beads with particle diameters ranging from 692 +/- 30 to 819 +/- 50 microm were obtained. The effect of drug content on the release of indomethacin from XG beads depended on the medium pH. Release of indomethacin from XG beads was retarded by coating with Eudragit and increased rapidly with the change in medium pH from 1.2 to 7.4. Adhesive force of XG was stronger than that of Carbopol 943 P, a well-known commercial mucoadhesive polymer, in wet state. Results indicate the enteric-coated XG beads may be suitable as a carrier for oral drug delivery of irritant drug in the stomach.

  18. Chitosan-based hydrogels for nasal drug delivery: from inserts to nanoparticles.

    PubMed

    Luppi, Barbara; Bigucci, Federica; Cerchiara, Teresa; Zecchi, Vittorio

    2010-07-01

    Chitosan represents a multifunctional polymer, featuring both mucoadhesive and permeation-enhancing properties and therefore is a widely studied excipient for mucosal drug delivery. As regards nasal administration, chitosans have been used for the preparation of gels, solid inserts, powders and nanoparticles in which a three-dimensional network can be recognized. This review provides a discussion of the different nasal dosage forms based on chitosan hydrogels. In the first section intranasal delivery is discuss as a useful tool for non-invasive administration of drugs intended for local or systemic treatments. Then chitosan-based hydrogels are described with a focus on their mucoadhesive and permeation-enhancing ability as well as their capacity of controlled drug release. Finally, a detailed discussion regarding several examples of the different nasal dosage forms is reported, including considerations on in vitro, ex vivo and in vivo studies. Summary and discussion of recent data on the different pharmaceutical forms based on chitosan hydrogels could be of interest to researchers dealing with nasal drug delivery. The aim of this review is to stimulate further investigations in order to achieve the collection of harmonized data and concrete clinical perspectives.

  19. Quantitative analysis of drug delivery to the brain via nasal route.

    PubMed

    Kozlovskaya, Luba; Abou-Kaoud, Mohammed; Stepensky, David

    2014-09-10

    The blood-brain barrier (BBB) prevents drugs' permeability into the brain and limits the management of brain diseases. Intranasal delivery is a convenient route of drug administration that can bypass the BBB and lead to a direct delivery of the drug to the brain. Indeed, drug accumulation in the brain following intranasal application of a drug solution, or of a drug encapsulated in specialized delivery systems (DDSs), has been reported in numerous scientific publications. We aimed to analyze the available quantitative data on drug delivery to the brain via the nasal route and to reveal the efficiency of brain drug delivery and targeting by different types of nasally-administered DDSs. We searched for scientific publications published in 1970-2014 that reported delivery of drugs or model compounds to the brain via intranasal and parenteral routes, and contained quantitative data that were sufficient for calculation of brain targeting efficiency. We identified 73 publications (that reported data on 82 compounds) that matched the search criteria and analyzed their experimental settings, formulation types, analytical methods, and the claimed efficiencies of drug brain targeting: drug targeting efficiency (%DTE) and nose-to-brain direct transport (%DTP). Outcomes of this analysis indicate that efficiency of brain delivery by the nasal route differs widely between the studies, and does not correlate with the drug's physicochemical properties. Particle- and gel-based DDSs offer limited advantage for brain drug delivery in comparison to the intranasal administration of drug solution. Nevertheless, incorporation of specialized reagents (e.g., absorption enhancers, mucoadhesive compounds, targeting residues) can increase the efficiency of drug delivery to the brain via the nasal route. More elaborate and detailed methodological and analytical characterizations and standardized reporting of the experimental outcomes are required for reliable quantification of drug targeting

  20. Mucoadhesive system formed by liquid crystals for buccal administration of poly(hexamethylene biguanide) hydrochloride.

    PubMed

    Souza, Carla; Watanabe, Evandro; Borgheti-Cardoso, Livia Neves; De Abreu Fantini, Márcia Carvalho; Lara, Marilisa Guimarães

    2014-12-01

    Antimicrobial approaches are valuable in controlling the development of buccal diseases, but some antibacterial agents have a short duration of activity. Therefore, the development of prolonged delivery systems would be advantageous. Liquid crystalline systems comprising monoolein (GMO)/water have been considered to be a potential vehicle to deliver drugs to the buccal mucosa because of the phase properties that allow for controlled drug release as well as its mucoadhesive properties. Therefore, the aim of this study was to develop a GMO/water system for the slow release of poly(hexamethylene biguanide) hydrochloride (PHMB) on the buccal mucosa and test the properties of this system with regard to swelling, release profile, antimicrobial activity, and strength of mucoadhesion, with the overall goal of treating buccal infections. The tested systems were capable of modulating drug release, which is controlled by diffusion of the drug throughout the system. Furthermore, PHMB appeared to improve the mucoadhesive properties of the system and may synergistically act with the drug to promote antimicrobial activity against S. mutas and C. albicans, indicating that liquid crystals may be suitable for the administration of PHMB on the buccal mucosa. Therefore, this system could be proposed as a novel system for mucoadhesive drug delivery.

  1. Formulation and Evaluation of In-vitro Characterization of Gastic-Mucoadhesive Microparticles/Discs Containing Metformin Hydrochloride

    PubMed Central

    Khonsari, Fatemeh; Zakeri-Milani, Parvin; Jelvehgari, Mitra

    2014-01-01

    The present study involves preparation and evaluation of gastric-mucoadhesive microparticles with Metformin Hydrochloride as model drug for prolongation of gastric residence time. The microparticles were prepared by the emulsification solvent evaporation technique using polymers of Carbomer 934p (CP) and Ethylcellulose (EC). The microparticles were prepared by emulsion solvent evaporation method (O1/O2). Disc formulations were prepared by direct compression technique from microparticles. In the current study, gastric-mucoadhesive microparticles with different polymers ratios (CP:EC) were prepared and were characterized by encapsulation efficiency, particle size, flowability, mucoadhesive property and drug release studies. The best polymers ratio was 1:3 (F2) with Carbomer 934p (as mucoadhesive polymer) and ethylcellulose (as retardant polymer), respectively. The production yield microparticles F2 showed 98.80%, mean particle size 933.25 µm and loading efficiency %98.44. The results were found that microparticle discs prepared had slower release than microparticles (p > o.o5). The microparticles exhibited very good percentage of mucoadhesion and flowability properties. The release of drug was prolonged to 8 h (71.65-82.22%) when incorporated into mucoadhesive microparticles. The poor bioavailability of metformine is attributed to short retention of its dosage form at the absorption sites (in upper gastrointestinal tract). The results of mucoadhesion study showed better retention of metformine microparticles (8 h) in duodenal and jejunum regions of intestine (F1, 1:2 ratio of CP:EC). Therefore, it may be concluded that drug loaded gastric-mucoadhesive microparticles are a suitable delivery system for metformin hydrochloride, and may be used for effective management of NIDDM (Non Insulin Dependent Diabetes Mellitus). PMID:24734057

  2. Implantable drug-delivery systems.

    PubMed

    Blackshear, P J

    1979-12-01

    Implantable drug-delivery systems are being developed to release drugs to the bloodstream continuously as well as free patients from being hospitalized to receive intravenous infusions or frequent injections. One technique is implantation of a pellet in the subcutaneous tissue so the pellet may be released by erosion. Drugs are also diffused through silicone rubber capsules but only polyacrylamide is able to release large molecules. Contraceptive rings containing progesterone and placed in the uterus or vagina and implanted silicone-rubber capsules use these principles. Disadvantages to the subcutaneous delivery of drugs include: 1) release of the drug in subcutaneous tissue rather than in the bloodstream directly; 2) entry into the circulatory system is controlled by surrounding blood supplies which vary with fat; 3) diffusion may be difficult due to dense layers of fibrous tissue; and 4) drug amounts cannot be readily regulated. The Ommaya reservoir uses a container with a self-sealing membrane implanted in the scalp and connected to a cerebral ventricle to treat forms of leukemia and fungal meningitis. Another development is an implantable disk-shaped infusion pump with 2 compartments, the outer one containing a propellant and the inner chamber containing the drug, holds 45 milliliters and releases about 1 milliliter/day. In the future these systems may release drugs in response to biochemical feedback or deliver a drug to 1 specific area.

  3. Enhanced vaginal drug delivery through the use of hypotonic formulations that induce fluid uptake

    PubMed Central

    Ensign, Laura M.; Hoen, Timothy; Maisel, Katharina; Cone, Richard; Hanes, Justin

    2013-01-01

    Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that administration of hypotonic solutions would induce fluid uptake that could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We found that hypotonic formulations markedly increased the rate at which small molecule drugs and muco-inert nanoparticles (mucus-penetrating particles, or MPP), but not conventional mucoadhesive nanparticles (CP), reached the vaginal epithelial surface in vivo in mice. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that drugs or MPP in isotonic formulations failed to reach efficiently. However, hypotonic formulations caused unencapsulated “free” drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for localized sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. In contrast, as we previously demonstrated, hypotonic delivery of drug via MPP led to better long-term retention and protection in the vagina. Importantly, we demonstrate that slightly hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. Hypotonic formulations for vaginal drug delivery via MPP may significantly improve prevention and treatment of reproductive tract diseases and disorders. PMID:23769419

  4. Chitosan gels for the vaginal delivery of lactic acid: relevance of formulation parameters to mucoadhesion and release mechanisms.

    PubMed

    Bonferoni, Maria Cristina; Giunchedi, Paolo; Scalia, Santo; Rossi, Silvia; Sandri, Giuseppina; Caramella, Carla

    2006-01-01

    The aim of this work was to assess the effect of formulation parameters of a mucoadhesive vaginal gel based on chitosan and lactic acid, and to highlight its release mechanisms. Two molecular weight chitosans were used to prepare gels with 2 lactic acid concentrations. Both chitosan molecular weight and lactic acid concentration had a significant and mutually dependent influence on mucoadhesion, measured on pig vaginal mucosa. Similarly, the lactate release profiles were found to be dependent on lactic acid content and polymer molecular weight. One gel formulation based on the stoichiometric lactate to chitosan ratio was subjected to release test in media with 2 different counterions and increasing ionic strength. This test demonstrated that the lactate release is mainly due to ionic displacement.

  5. Nanoparticles for Brain Drug Delivery

    PubMed Central

    Masserini, Massimo

    2013-01-01

    The central nervous system, one of the most delicate microenvironments of the body, is protected by the blood-brain barrier (BBB) regulating its homeostasis. BBB is a highly complex structure that tightly regulates the movement of ions of a limited number of small molecules and of an even more restricted number of macromolecules from the blood to the brain, protecting it from injuries and diseases. However, the BBB also significantly precludes the delivery of drugs to the brain, thus, preventing the therapy of a number of neurological disorders. As a consequence, several strategies are currently being sought after to enhance the delivery of drugs across the BBB. Within this review, the recently born strategy of brain drug delivery based on the use of nanoparticles, multifunctional drug delivery systems with size in the order of one-billionth of meters, is described. The review also includes a brief description of the structural and physiological features of the barrier and of the most utilized nanoparticles for medical use. Finally, the potential neurotoxicity of nanoparticles is discussed, and future technological approaches are described. The strong efforts to allow the translation from preclinical to concrete clinical applications are worth the economic investments. PMID:25937958

  6. Effect of low-molecular-weight beta-cyclodextrin polymer on release of drugs from mucoadhesive buccal film dosage forms.

    PubMed

    Arakawa, Yotaro; Kawakami, Shigeru; Yamashita, Fumiyoshi; Hashida, Mitsuru

    2005-09-01

    We investigated the effect of low-molecular-weight beta-cyclodextrin (beta-CyD) polymer on in vitro release of two drugs with different lipophilicities (i.e., lidocaine and ketoprofen) from mucoadhesive buccal film dosage forms. When beta-CyD polymer was added to hydroxypropylcellulose (HPC) or polyvinylalcohol (PVA) film dosage forms, the release of lidocaine into artificial saliva (pH 5.7) was reduced by 40% of the control. In contrast, the release of ketoprofen from the polymer film was enhanced by addition of beta-CyD polymer to the vehicle. When lidocaine and ketoprofen was incubated with beta-CyD polymer in the artificial saliva, concentration of free lidocaine molecules decreased in a beta-CyD polymer concentration-dependent manner. The association constant with beta-CyD polymer was 6.9+/-0.6 and 520+/-90 M(-1) for lidocaine and ketoprofen, respectively. Retarded release of the hydrophilic lidocaine by beta-CyD polymer might be due to the decrease in thermodynamic activity by inclusion complex formation, whereas enhanced release of the lipophilic ketoprofen by the beta-CyD polymer might be due to prevention of recrystallization occurring after contacting the film with aqueous solution. Thus, effects of low-molecular-weight beta-CyD polymer to the drug release rate from film dosage forms would vary according to the strength of interaction with and the solubility of active ingredient.

  7. Preparation of thiomer microparticles and in vitro evaluation of parameters influencing their mucoadhesive properties.

    PubMed

    Albrecht, K; Zirm, E J; Palmberger, T F; Schlocker, W; Bernkop-Schnürch, A

    2006-01-01

    It was the aim of this study to develop mucoadhesive microparticulate delivery systems based on thiomers and to investigate parameters influencing their mucoadhesive properties. Microparticles were prepared via coazervation of thiolated or unmodified polycarbophil with fluorescein-diacetate as marker. The protective effect of the polymers toward enzymatic hydrolysis by intestinal enzymes was investigated. Mucoadhesion studies with microparticles, applied in dry and prehydrated form, were performed by ascertaining their residence time on intestinal mucosa. Furthermore, the influence of the amount of thiol groups on mucoadhesion was studied in vitro. Results showed that in comparison to unmodified polycarbophil, thiolated polycarbophil provided a more than 3-fold higher protective effect for the incorporated marker fluorescein-diacetate toward hydrolysis. When being applied in dry form 23.4 +/- 4.8% of the fluorescence marker being embedded in thiomer microparticles remained adhering to the intestinal mucosa within 3 h. In contrast, only 11.6 +/- 2.0% of the marker remained on the mucosa, when the thiomer microparticles were applied in prehydrated form. In addition, tests performed to assess the impact of the amount of thiol groups pointed out that a high amount of thiol groups is advantageous in order to further improve mucoadhesive properties. This knowledge should contribute to the design of highly efficient drug delivery systems being based on thiomer microparticles.

  8. Formulation and Characterization of Oral Mucoadhesive Chlorhexidine Tablets Using Cordia myxa Mucilage

    PubMed Central

    Moghimipour, Eskandar; Aghel, Nasrin; Adelpour, Akram

    2012-01-01

    Background The dilution and rapid elimination of topically applied drugs due to the flushing action of saliva is a major difficulty in the effort to eradicate infections of oral cavity. Utilization a proper delivery system for incorporation of drugs has a major impact on drug delivery and such a system should be formulated for prolonged drug retention in oral cavity. Objectives The aim of the present study was the use of mucilage of Cordia myxa as a mucoadhesive material in production of chlorhexidine buccal tablets and its substitution for synthetic polymers such as HPMC. Materials and Methods The influence of mucilage concentration on the physicochemical responses (hardness, friability, disintegration time, dissolution, swelling, and muco-adhesiveness strength) was studied and swelling of mucilage and HPMC were compared. The evaluated responses included pharmacopoeial characteristics of tablets, the force needed to separate tablets from mucosa, and the amount of water absorbed by tablets. Results In comparison to HPMC, the rise of mucilage concentration in the formulations increased disintegration time, drug dissolution rate, and reduced MDT. Also, compared to 30% HPMC, muco-adhesiveness strength of buccal tablets containing 20% mucilage was significantly higher. Conclusions It can be concluded that the presence of Cordia myxa powdered mucilage may significantly affect the tablet characteristics, and increasing in muco-adhesiveness may be achieved by using 20% w/w mucilage. PMID:24624170

  9. A mechanistic based approach for enhancing buccal mucoadhesion of chitosan.

    PubMed

    Meng-Lund, Emil; Muff-Westergaard, Christian; Sander, Camilla; Madelung, Peter; Jacobsen, Jette

    2014-01-30

    Mucoadhesive buccal drug delivery systems can enhance rapid drug absorption by providing an increased retention time at the site of absorption and a steep concentration gradient. An understanding of the mechanisms behind mucoadhesion of polymers, e.g. chitosan, is necessary for improving the mucoadhesiveness of buccal formulations. The interaction between chitosan of different chain lengths and porcine gastric mucin (PGM) was studied using a complex coacervation model (CCM), isothermal titration calorimetry (ITC) and a tensile detachment model (TDM). The effect of pH was assessed in all three models and the approach to add a buffer to chitosan based drug delivery systems is a means to optimize and enhance buccal drug absorption. The CCM demonstrated optimal interactions between chitosan and PGM at pH 5.2. The ITC experiments showed a significantly increase in affinity between chitosan and PGM at pH 5.2 compared to pH 6.3 and that the interactions were entropy driven. The TDM showed a significantly increase in strength of adhesion between chitosan discs and an artificial mucosal surface at pH 5.2 compared to pH 6.8, addition of PGM increased the total work of adhesion by a factor of 10 as compared to the wetted surface without PGM. These findings suggest that chitosan and PGM are able to interact by electrostatic interactions and by improving the conditions for electrostatic interactions, the adhesion between chitosan and PGM becomes stronger. Also, the three complementary methods were utilized to conclude the pH dependency on mucoadhesiveness.

  10. Drug delivery by lipid cochleates.

    PubMed

    Zarif, Leila

    2005-01-01

    Drug delivery technology has brought additional benefits to pharmaceuticals such as reduction in dosing frequency and side effects, as well as the extension of patient life. To address this need, cochleates, a precipitate obtained as a result of the interaction between phosphatidylserine and calcium, have been developed and proved to have potential in encapsulating and delivering small molecule drugs. This chapter discusses the molecules that can be encapsulated in a cochleate system and describes in detail the methodology that can be used to encapsulate and characterize hydrophobic drugs such as amphotericin B, a potent antifungal agent. Some efficacy data in animal models infected with candidiasis or aspergillosis are described as well.

  11. Microfabricated injectable drug delivery system

    DOEpatents

    Krulevitch, Peter A.; Wang, Amy W.

    2002-01-01

    A microfabricated, fully integrated drug delivery system capable of secreting controlled dosages of multiple drugs over long periods of time (up to a year). The device includes a long and narrow shaped implant with a sharp leading edge for implantation under the skin of a human in a manner analogous to a sliver. The implant includes: 1) one or more micromachined, integrated, zero power, high and constant pressure generating osmotic engine; 2) low power addressable one-shot shape memory polymer (SMP) valves for switching on the osmotic engine, and for opening drug outlet ports; 3) microfabricated polymer pistons for isolating the pressure source from drug-filled microchannels; 4) multiple drug/multiple dosage capacity, and 5) anisotropically-etched, atomically-sharp silicon leading edge for penetrating the skin during implantation. The device includes an externally mounted controller for controlling on-board electronics which activates the SMP microvalves, etc. of the implant.

  12. Bionanocomposites based on layered double hydroxides as drug delivery systems

    NASA Astrophysics Data System (ADS)

    Aranda, Pilar; Alcântara, Ana C. S.; Ribeiro, Ligia N. M.; Darder, Margarita; Ruiz-Hitzky, Eduardo

    2012-10-01

    The present work introduces new biohybrid materials involving layered double hydroxides (LDH) and biopolymers to produce bionanocomposites, able to act as effective drug delivery systems (DDS). Ibuprofen (IBU) and 5-aminosalicylic acid (5-ASA) have been chosen as model drugs, being intercalated in a Mg-Al LDH matrix. On the one side, the LDHIBU intercalation compound prepared by ion-exchange reaction was blended with the biopolymers zein, a highly hydrophobic protein, and alginate, a polysaccharide widely applied for encapsulating drugs. On the other side, the LDH- 5-ASA intercalation compound prepared by co-precipitation was assembled to the polysaccharides chitosan and pectin, which show mucoadhesive properties and resistance to acid pH values, respectively. Characterization of the intercalation compounds and the resulting bionanocomposites was carried out by means of different experimental techniques: X-ray diffraction, infrared spectroscopy, chemical and thermal analysis, as well as optical and scanning electron microscopies. Data on the swelling behavior and drug release under different pH conditions are also reported.

  13. Mucoadhesive Hydrogel Films of Econazole Nitrate: Formulation and Optimization Using Factorial Design

    PubMed Central

    Gajra, Balaram; Pandya, Saurabh S.; Singh, Sanjay; Rabari, Haribhai A.

    2014-01-01

    The mucoadhesive hydrogel film was prepared and optimized for the purpose of local drug delivery to oral cavity for the treatment of oral Candidiasis. The mucoadhesive hydrogel film was prepared with the poly(vinyl alcohol) by freeze/thaw crosslinking technique. 32 full factorial design was employed to optimize the formulation. Number of freeze/thaw cycles (4, 6, and 8 cycles) and the concentration of the poly(vinyl alcohol) (10, 15, and 20%) were used as the independent variables whereas time required for 50% drug release, cumulative percent of drug release at 8th hour, and “k” of zero order equation were used as the dependent variables. The films were evaluated for mucoadhesive strength, in vitro residence time, swelling study, in vitro drug release, and effectiveness against Candida albicans. The concentration of poly(vinyl alcohol) and the number of freeze/thaw cycles both decrease the drug release rate. Mucoadhesive hydrogel film with 15% poly(vinyl alcohol) and 7 freeze/thaw cycles was optimized. The optimized batch exhibited the sustained release of drug and the antifungal studies revealed that the drug released from the film could inhibit the growth of Candida albicans for 12 hours. PMID:25006462

  14. Crosslinked chitosan-dextran sulfate nanoparticle for improved topical ocular drug delivery

    PubMed Central

    Chaiyasan, Wanachat; Srinivas, Sangly P.

    2015-01-01

    Purpose To examine the benefits of chitosan-dextran sulfate nanoparticles (CDNs) as a topical ocular delivery system with lutein as a model drug. Methods CDNs were developed by polyelectrolyte complexation of positively charged chitosan (CS) and negatively charged dextran sulfate (DS). 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and polyethylene glycol 400 (PEG400) were used as co-crosslinking and stabilizing agents, respectively. The influence of these on the properties of CDNs, including drug release and mucoadhesiveness, was examined. The chemical stability of lutein in CDNs (LCDNs) was also examined. Results Typically, LCDNs showed a spherical shape, possessing a mean size of ~400 nm with a narrow size distribution. The entrapment efficiency of lutein was in the range of 60%–76%. LCDNs possessing a positive surface charge (+46 mV) were found to be mucoadhesive. The release profile of LCDNs followed Higuchi’s square root model, suggesting drug release by diffusion from the polymer matrix. Lutein in LCDNs showed increased chemical stability during storage compared to its solution form. Conclusions These characteristics of CDNs make them suitable for drug delivery to the ocular surface. PMID:26604662

  15. Protease-mediated drug delivery

    NASA Astrophysics Data System (ADS)

    Dickson, Eva F.; Goyan, Rebecca L.; Kennedy, James C.; Mackay, M.; Mendes, M. A. K.; Pottier, Roy H.

    2003-12-01

    Drugs used in disease treatment can cause damage to both malignant and normal tissue. This toxicity limits the maximum therapeutic dose. Drug targeting is of high interest to increase the therapeutic efficacy of the drug without increasing systemic toxicity. Certain tissue abnormalities, disease processes, cancers, and infections are characterized by high levels of activity of specific extracellular and/or intracellular proteases. Abnormally high activity levels of specific proteases are present at sites of physical or chemical trauma, blood clots, malignant tumors, rheumatoid arthritis, inflammatory bowel disease, gingival disease, glomerulonerphritis, and acute pancreatitis. Abnormal protease activity is suspected in development of liver thrombosis, pulmonary emphysema, atherosclerosis, and muscular dystrophy. Inactiviating disease-associated proteases by the administration of appropriate protease inhibitors has had limited success. Instead, one could use such proteases to target drugs to treat the condition. Protease mediated drug delivery offers such a possibility. Solubilizing groups are attached to insoluble drugs via a polypeptide chain which is specifically cleavable by certian proteases. When the solubilized drug enounters the protease, the solubilizing moieties are cleaved, and the drug precipitates at the disease location. Thus, a smaller systemic dosage could result in a therapeutic drug concentration at the treatment site with less systemic toxicity.

  16. Ultrasound mediated nanoparticle drug delivery

    NASA Astrophysics Data System (ADS)

    Mullin, Lee B.

    Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems

  17. Polymeric Nanoparticle Drug Delivery Technologies for Oral Delivery Applications

    PubMed Central

    Pridgen, Eric M.; Alexis, Frank; Farokhzad, Omid C.

    2016-01-01

    Introduction Many therapeutics are limited to parenteral administration. Oral administration is a desirable alternative because of the convenience and increased compliance by patients, especially for chronic diseases that require frequent administration. Polymeric nanoparticles are one technology being developed to enable clinically feasible oral delivery. Areas covered This review discusses the challenges associated with oral delivery. Strategies used to overcome gastrointestinal barriers using polymeric nanoparticles will be considered, including mucoadhesive biomaterials and targeting of nanoparticles to transcytosis pathways associated with M cells and enterocytes. Applications of oral delivery technologies will also be discussed, such as oral chemotherapies, oral insulin, treatment of inflammatory bowel disease, and mucosal vaccinations. Expert opinion There have been many approaches used to overcome the transport barriers presented by the gastrointestinal tract, but most have been limited by low bioavailability. Recent strategies targeting nanoparticles to transcytosis pathways present in the intestines have demonstrated that it is feasible to efficiently transport both therapeutics and nanoparticles across the intestines and into systemic circulation after oral administration. Further understanding of the physiology and pathophysiology of the intestines could lead to additional improvements in oral polymeric nanoparticle technologies and enable the translation of these technologies to clinical practice. PMID:25813361

  18. Food, physiology and drug delivery.

    PubMed

    Varum, F J O; Hatton, G B; Basit, A W

    2013-12-05

    Gastrointestinal physiology is dynamic and complex at the best of times, and a multitude of known variables can affect the overall bioavailability of drugs delivered via the oral route. Yet while the influences of food and beverage intake as just two of these variables on oral drug delivery have been extensively documented in the wider literature, specific information on their effects remains sporadic, and is not so much contextually reviewed. Food co-ingestion with oral dosage forms can mediate several changes to drug bioavailability, yet the precise mechanisms underlying this have yet to be fully elucidated. Likewise, the often detrimental effects of alcohol (ethanol) on dosage form performance have been widely observed experimentally, but knowledge of which has only moderately impacted on clinical practice. Here, we attempt to piece together the available subject matter relating to the influences of both solid and liquid foodstuffs on the gastrointestinal milieu and the implications for oral drug delivery, with particular emphasis on the behaviour of modified-release dosage forms, formulation robustness and drug absorption. Providing better insight into these influences, and exemplifying cases where formulations have been developed or modified to circumvent their associated problems, can help to appropriately direct the design of future in vitro digestive modelling systems as well as oral dosage forms resilient to these effects. Moreover, this will help to better our understanding of the impact of food and alcohol intake on normal gut behaviour and function.

  19. A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods

    PubMed Central

    Chinna Reddy, P; Chaitanya, K.S.C.; Madhusudan Rao, Y.

    2011-01-01

    Owing to the ease of the administration, the oral cavity is an attractive site for the delivery of drugs. Through this route it is possible to realize mucosal (local effect) and transmucosal (systemic effect) drug administration. In the first case, the aim is to achieve a site-specific release of the drug on the mucosa, whereas the second case involves drug absorption through the mucosal barrier to reach the systemic circulation. The main obstacles that drugs meet when administered via the buccal route derive from the limited absorption area and the barrier properties of the mucosa. The effective physiological removal mechanisms of the oral cavity that take the formulation away from the absorption site are the other obstacles that have to be considered. The strategies studied to overcome such obstacles include the employment of new materials that, possibly, combine mucoadhesive, enzyme inhibitory and penetration enhancer properties and the design of innovative drug delivery systems which, besides improving patient compliance, favor a more intimate contact of the drug with the absorption mucosa. This presents a brief description of advantages and limitations of buccal drug delivery and the anatomical structure of oral mucosa, mechanisms of drug permeation followed by current formulation design in line with developments in buccal delivery systems and methodology in evaluating buccal formulations. PMID:23008684

  20. Mucoadhesive films as perspective oral dosage form.

    PubMed

    Landová, Hana; Daněk, Zdeněk; Gajdziok, Jan; Vetchý, David; Stembírek, Jan

    2013-02-01

    Mucoadhesion is a specific phenomenon of creating bonds during intimate contact between biological surfaces covered by a mucus layer and a mucoadhesive material. In recent years come to the forefront of interest in the pharmaceutical industry modern dosage forms based on this specific process. Films (discs, patches) composed of mucoadhesive polymers (cellulose derivatives, polyacrylates, polyoxyethylene, etc.) prepared by established methods (solvent casting, hot melt extrusion, etc.) could be perspective candidates for oral administration of many drugs due to their flexibility and comfortable use. In addition, they can circumvent the relatively short residence time of conventional oral dosage forms on the mucosa and provide a precisely measured drug dose to the application site. Moreover, they can also help to protect the wound surface, thus help to reduce pain and improve effectiveness of the therapy. The aim of this article is to give an overview about the principles of creation of mucoadhesive bonds and about novel dosage form - mucoadhesive films in terms of their composition, preparation and practical usage. oral mucosa mucoadhesion principles mucoadhesive dosage forms films patches discs.

  1. Superhydrophobic materials for drug delivery

    NASA Astrophysics Data System (ADS)

    Yohe, Stefan Thomas

    Superhydrophobicity is a property of material surfaces reflecting the ability to maintain air at the solid-liquid interface when in contact with water. These surfaces have characteristically high apparent contact angles, by definition exceeding 150°, as a result of the composite material-air surface formed under an applied water droplet. Superhydrophobic surfaces were first discovered on naturally occurring substrates, and have subsequently been fabricated in the last several decades to harness these favorable surface properties for a number of emerging applications, including their use in biomedical settings. This work describes fabrication and characterization of superhydrophobic 3D materials, as well as their use as drug delivery devices. Superhydrophobic 3D materials are distinct from 2D superhydrophobic surfaces in that air is maintained not just at the surface of the material, but also within the bulk. When the superhydrophobic 3D materials are submerged in water, water infiltrates slowly and continuously as a new water-air-material interface is formed with controlled displacement of air. Electrospinning and electrospraying are used to fabricate superhydrophobic 3D materials utilizing blends of the biocompatible polymers poly(epsilon-caprolactone) and poly(caprolactone-co-glycerol monostearate) (PGC-C18). PGC-C18 is significantly more hydrophobic than PCL (contact angle of 116° versus 83° for flat materials), and further additions of PGC-C18 into electrospun meshes and electrosprayed coatings affords increased stability of the entrapped air layer. For example, PCL meshes alone (500 mum thick) take 10 days to fully wet, and with 10% or 30% PGC-C18 addition wetting rates are dramatically slowed to 60% wetted by 77 days and 4% by 75 days, respectively. Stability of the superhydrophobic materials can be further probed with a variety of physio-chemical techniques, including pressure, surfactant containing solutions, and solvents of varying surface tension

  2. In situ forming implants for the delivery of metronidazole to periodontal pockets: formulation and drug release studies.

    PubMed

    Kilicarslan, Muge; Koerber, Martin; Bodmeier, Roland

    2014-05-01

    This study was performed to obtain prolonged drug release with biodegradable in situ forming implants for the local delivery of metronidazole to periodontal pockets. The effect of polymer type (capped and uncapped PLGA), solvent type (water-miscible and water-immiscible) and the polymer/drug ratio on in vitro drug release studies were investigated. In situ implants with sustained metronidazole release and low initial burst consisted of capped PLGA and N-methyl-2-pyrolidone as solvent. Mucoadhesive polymers were incorporated into the in situ implants in order to modify the properties of the delivery systems towards longer residence times in vivo. Addition of the polymers changed the adhesiveness and increased the viscosity and drug release of the formulations. However, sustained drug release over 10 days was achievable. Biodegradable in situ forming implants are therefore an attractive delivery system to achieve prolonged release of metronidazole at periodontal therapy.

  3. Thermosensitive polymers for drug delivery

    SciTech Connect

    Gutowska, A.; Kim, Sung Wan

    1996-12-31

    Thermosensitive polymers (TSP) demonstrating temperature-dependent temperature-dependent swelling in water have been extensively studied in recent years. Their molecular and physical properties have been tailored for a variety of biomedical and engineering uses. This presentation will discuss TSP based on poly(N-isopropylacrylamide) and its crosslinked networks modified with hydrophobic or hydrophilic components by copolymerization blending and formation of interpenetrating polymer networks (IPNs). TSP designed for three different areas of drug delivery will be presented. First, heparin releasing temperature-sensitive polymers for the prevention of surface induced thrombosis will be presented as an example of a local macromolecular delivery from a surface of a medical device. Second, a new oral delivery device based on a novel mechanical squeezing concept, utilizing specific swelling-deswelling characteristics of temperature- and temperature/pH-sensitive hydrogels will be described. These hydrogels were synthesized to exhibit a controlled swelling-deswelling kinetics, hence a variety of release profiles may be generated: a delayed, a zero-order or an {open_quotes}on-off{close_quotes} release profile. Finally, thermally reversible polymeric gels as an extracellular matrix for the entrapment of pancreatic islet cells in biohybrid artificial pancreas for insulin delivery will be discussed.

  4. Linear correlation between rheological, mechanical and mucoadhesive properties of polycarbophil polymer blends for biomedical applications.

    PubMed

    De Souza Ferreira, Sabrina Barbosa; Da Silva, Jéssica Bassi; Borghi-Pangoni, Fernanda Belincanta; Junqueira, Mariana Volpato; Bruschi, Marcos Luciano

    2017-02-14

    Polycarbophil is widely used in a variety of pharmaceutical formulations, mainly for their strong ability to adhere to the epithelial and mucous barriers (bio/mucoadhesion). On the other hand, its association with the thermoresponsive polymer (poloxamer 407) has been poorly explored. This work investigates the rheological, mechanical and mucoadhesive properties of polymer blends containing polycarbophil and poloxamer 407, in order to select the best formulations for biomedical and pharmaceutical applications. Mechanical (hardness, compressibility, adhesiveness, softness, and mucoadhesion) and rheological characteristics (consistency index, yield value and hysteresis area) showed that 20% (w/w) poloxamer 407- polymer blends exhibited higher values parameters. However, the rheological interaction parameter, which was more sensible than the mechanical interaction parameter, revealed higher synergism for systems comprising 15% (w/w) poloxamer 407, due to the system organization and polymers' properties. Furthermore, gelation temperatures were appropriated, suggesting that polymer blends can be used as biomedical materials, and displaying easy administration, enhanced retention and prolonged residence time at the site of application. Therefore, rheological, mechanical and mucoadhesive characterization provided a rational basis for selecting appropriated systems, useful for mucoadhesive drug delivery systems and biomedical applications.

  5. Microspheres and Nanotechnology for Drug Delivery.

    PubMed

    Jóhannesson, Gauti; Stefánsson, Einar; Loftsson, Thorsteinn

    2016-01-01

    Ocular drug delivery to the posterior segment of the eye can be accomplished by invasive drug injections into different tissues of the eye and noninvasive topical treatment. Invasive treatment involves the risks of surgical trauma and infection, and conventional topical treatments are ineffective in delivering drugs to the posterior segment of the eye. In recent years, nanotechnology has become an ever-increasing part of ocular drug delivery. In the following, we briefly review microspheres and nanotechnology for drug delivery to the eye, including different forms of nanotechnology such as nanoparticles, microparticles, liposomes, microemulsions and micromachines. The permeation barriers and anatomical considerations linked to ocular drug delivery are discussed and a theoretical overview on drug delivery through biological membranes is given. Finally, in vitro, in vivo and human studies of x03B3;-cyclodextrin nanoparticle eyedrop suspensions are discussed as an example of nanotechnology used for drug delivery to the eye.

  6. Drug delivery systems from nose to brain.

    PubMed

    Misra, Ambikanandan; Kher, Gitanjali

    2012-09-01

    The treatment of brain disorders is particularly challenging due to the presence of a variety of formidable obstacles to deliver drugs selectively and effectively to the brain. Blood-brain-barrier (BBB) constitutes the major obstacle to the uptake of drugs into the brain following systemic administration. Intranasal delivery offers a non-invasive and convenient method to bypass the BBB and delivery of therapeutics directly to the brain. The review discusses the potential of intranasal route to deliver drugs to the brain, the mechanisms and pathways of direct nose to brain drug transport, the various factors influencing transnasal drug absorption, the conventional and novel intranasal drug delivery systems, the various intranasal drug delivery techniques and devices, and examples of brain drug transport that have been feasible in treating various brain disorders. Moreover, products on the market, investigational drugs, and the author's perceptions about the prospect of intranasal delivery for treating brain disorders are also been discussed.

  7. Ocular drug delivery systems: An overview

    PubMed Central

    Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

    2014-01-01

    The major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments

  8. Device-assisted transdermal drug delivery.

    PubMed

    Lee, Hyunjae; Song, Changyeong; Baik, Seungmin; Kim, Dokyoon; Hyeon, Taeghwan; Kim, Dae-Hyeong

    2017-09-01

    Transdermal drug delivery is a prospective drug delivery strategy to complement the limitations of conventional drug delivery systems including oral and injectable methods. This delivery route allows both convenient and painless drug delivery and a sustained release profile with reduced side effects. However, physiological barriers in the skin undermine the delivery efficiency of conventional patches, limiting drug candidates to small-molecules and lipophilic drugs. Recently, transdermal drug delivery technology has advanced from unsophisticated methods simply relying on natural diffusion to drug releasing systems that dynamically respond to external stimuli. Furthermore, physical barriers in the skin have been overcome using microneedles, and controlled delivery by wearable biosensors has been enabled ultimately. In this review, we classify the evolution of advanced drug delivery strategies based on generations and provide a comprehensive overview. Finally, the recent progress in advanced diagnosis and therapy through customized drug delivery systems based on real-time analysis of physiological cues is highlighted. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Colloidal drug delivery systems in vaccine delivery.

    PubMed

    Beg, Sarwar; Samad, Abdus; Nazish, Iram; Sultana, Ruksar; Rahman, Mahfoozur; Ahmad, Md Zaki; Akbar, Md

    2013-01-01

    Vaccines play a vital role in the field of community medicine to combat against several diseases of human existence. Vaccines primarily trigger the acquired immune system to develop long-lasting immunity against pathogens. Conventional approaches for vaccine delivery lacks potential to target a particular antigen to develop acquired immunity by specific antibodies. Recent advancements in vaccine delivery showed that inclusion of adjuvants in vaccine formulations or delivery of them in a carrier helps in achieving desired targeting ability, reducing the immunogenicity and significant augmentation in the immune response. Colloidal carriers (liposomes, niosomes, microspheres, proteosomes, virosomes and virus like particles (VLPs), antigen cochleates, dendrimers and carbon nanotubes) have been widely explored for vaccine delivery. Further, surface engineering of these carriers with ligands, functional moieties and monoclonal antibodies tend to enhance the immune recognition potential of vaccines by differentiation of antigen specific memory T-cells. The current review, therefore, provides an updated account on the recent advancements in various colloidal delivery systems in vaccine delivery, outlining the mechanism of immune response initiated by them along with potential applications and marketed instances in an explicit manner.

  10. Preparation of Mucoadhesive Oral Patches Containing Tetracycline Hydrochloride and Carvacrol for Treatment of Local Mouth Bacterial Infections and Candidiasis

    PubMed Central

    Obaidat, Rana M.; Bader, Ammar; Al-Rajab, Wafa; Abu Sheikha, Ghassan; Obaidat, Aiman A.

    2011-01-01

    The specific aim of this work was to prepare mucoadhesive patches containing tetracycline hydrochloride and carvacrol in an attempt to develop a novel oral drug delivery system for the treatment of mouth infections. The bilayered patches were prepared using ethyl cellulose as a backing layer and carbopol 934 as a matrix mucoadhesive layer. Patches were prepared with different loading amounts of tetracycline hydrochloride and carvacrol. The antimicrobial activity was assessed for the prepared patches using the disc-diffusion method against the yeast Candida albicans and five bacterial strains, including Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Bacillus bronchispti. In this work, we highlighted the possibility of occurrence of a synergistic action between carvacrol and tetracycline. The best formulation was selected based on microbiological tests, drug release, ex-vivo mucoadhesive performance, and swelling index. Physical characteristics of the selected formulations were determined. These included pH, patch thickness, weight uniformity, content uniformity, folding endurance, and patch stability. PMID:21617783

  11. Integrated microsystems for controlled drug delivery.

    PubMed

    Razzacki, S Zafar; Thwar, Prasanna K; Yang, Ming; Ugaz, Victor M; Burns, Mark A

    2004-02-10

    Efficient drug delivery and administration are needed to realize the full potential of molecular therapeutics. Integrated microsystems that incorporate extremely fast sensory and actuation capabilities can fulfill this need for efficient drug delivery tools. Photolithographic technologies borrowed from the semiconductor industry enable mass production of such microsystems. Rapid prototyping allows for the quick development of customized devices that would accommodate for diverse therapeutic requirements. This paper reviews the capabilities of existing microfabrication and their applications in controlled drug delivery microsystems. The next generation of drug delivery systems--fully integrated and self-regulating--would not only improve drug administration, but also revolutionize the health-care industry.

  12. Microemulsion-based drug delivery system for transnasal delivery of Carbamazepine: preliminary brain-targeting study.

    PubMed

    Patel, Rashmin Bharatbhai; Patel, Mrunali Rashmin; Bhatt, Kashyap K; Patel, Bharat G; Gaikwad, Rajiv V

    2016-01-01

    This study reports the development and evaluation of Carbamazepine (CMP)-loaded microemulsions (CMPME) for intranasal delivery in the treatment of epilepsy. The CMPME was prepared by the spontaneous emulsification method and characterized for physicochemical parameters. All formulations were radiolabeled with (99m)Tc (technetium) and biodistribution of CMP in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging in rats was also performed to determine the uptake of the CMP into the brain. CMPME were found crystal clear and stable with average globule size of 34.11 ± 1.41 nm. (99m)Tc-labeled CMP solution (CMPS)/CMPME/CMP mucoadhesive microemulsion (CMPMME) were found to be stable and suitable for in vivo studies. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of CMPMME compared to intravenous CMPME was found to be 2- to 3-fold higher signifying larger extent of distribution of the CMP in brain. Drug targeting efficiency and direct drug transport were found to be highest for CMPMME post-intranasal administration compared to intravenous CMP. Rat brain scintigraphy also demonstrated higher intranasal uptake of the CMP into the brain. This investigation demonstrates a prompt and larger extent of transport of CMP into the brain through intranasal CMPMME, which may prove beneficial for treatment of epilepsy.

  13. Ungual and transungual drug delivery.

    PubMed

    Shivakumar, H N; Juluri, Abhishek; Desai, B G; Murthy, S Narasimha

    2012-08-01

    Topical therapy is desirable in treatment of nail diseases like onychomycosis (fungal infection of nail) and psoriasis. The topical treatment avoids the adverse effects associated with systemic therapy, thereby enhancing the patient compliance and reducing the treatment cost. However the effectiveness of the topical therapies has been limited due to the poor permeability of the nail plate to topically applied therapeutic agents. Research over the past one decade has been focused on improving the transungual permeability by means of chemical treatment, penetration enhancers, mechanical and physical methods. The present review is an attempt to discuss the different physical and chemical methods employed to increase the permeability of the nail plate. Minimally invasive electrically mediated techniques such as iontophoresis have gained success in facilitating the transungual delivery of actives. In addition drug transport across the nail plate has been improved by filing the dorsal surface of the nail plate prior to application of topical formulation. But attempts to improve the trans-nail permeation using transdermal chemical enhancers have failed so far. Attempts are on to search suitable physical enhancement techniques and chemical transungual enhancers in view to maximize the drug delivery across the nail plate.

  14. Polymeric conjugates for drug delivery

    PubMed Central

    Larson, Nate; Ghandehari, Hamidreza

    2012-01-01

    The field of polymer therapeutics has evolved over the past decade and has resulted in the development of polymer-drug conjugates with a wide variety of architectures and chemical properties. Whereas traditional non-degradable polymeric carriers such as poly(ethylene glycol) (PEG) and N-(2-hydroxypropyl methacrylamide) (HPMA) copolymers have been translated to use in the clinic, functionalized polymer-drug conjugates are increasingly being utilized to obtain biodegradable, stimuli-sensitive, and targeted systems in an attempt to further enhance localized drug delivery and ease of elimination. In addition, the study of conjugates bearing both therapeutic and diagnostic agents has resulted in multifunctional carriers with the potential to both “see and treat” patients. In this paper, the rational design of polymer-drug conjugates will be discussed followed by a review of different classes of conjugates currently under investigation. The design and chemistry used for the synthesis of various conjugates will be presented with additional comments on their potential applications and current developmental status. PMID:22707853

  15. Ligand-Targeted Drug Delivery.

    PubMed

    Srinivasarao, Madduri; Low, Philip S

    2017-09-12

    Safety and efficacy constitute the major criteria governing regulatory approval of any new drug. The best method to maximize safety and efficacy is to deliver a proven therapeutic agent with a targeting ligand that exhibits little affinity for healthy cells but high affinity for pathologic cells. The probability of regulatory approval can conceivably be further enhanced by exploiting the same targeting ligand, conjugated to an imaging agent, to select patients whose diseased tissues display sufficient targeted receptors for therapeutic efficacy. The focus of this Review is to summarize criteria that must be met during design of ligand-targeted drugs (LTDs) to achieve the required therapeutic potency with minimal toxicity. Because most LTDs are composed of a targeting ligand (e.g., organic molecule, aptamer, protein scaffold, or antibody), spacer, cleavable linker, and therapeutic warhead, criteria for successful design of each component will be described. Moreover, because obstacles to successful drug design can differ among human pathologies, limitations to drug delivery imposed by the unique characteristics of different diseases will be considered. With the explosion of genomic and transcriptomic data providing an ever-expanding selection of disease-specific targets, and with tools for high-throughput chemistry offering an escalating diversity of warheads, opportunities for innovating safe and effective LTDs has never been greater.

  16. Mucoadhesive Nanostructured Polyelectrolyte Complexes as Potential Carrier to Improve Zidovudine Permeability.

    PubMed

    Pedreiro, Liliane Neves; Stringhetti, Beatriz; Cury, Ferreira; Gremião, Maria Palmira Daflon

    2016-02-01

    Mucoadhesive drug delivery systems have been widely investigated as a strategic to allow the raising of intestinal residence time of drugs and the intimate contact with the intestinal mucosa, both factors that increase the local concentration gradient. Zidovudine (AZT) mucoadhesive nanostructured polyelectrolyte complexes were obtained by chitosan (CS)-hypromellose phthalate (HP) interactions in order to favor the permeability through biological membranes and the AZT absorption. Particle size and morphology analyses showed the obtaining of nanoparticulate delivery systems, with AZT loaded about of 65%. The characterization by DSC, X-ray diffraction and FTIR showed a new crystalline structure formed in which the drug remained molecularly dispersed, without changing this structure. The reduced release rates in the simulated gastric medium and the control of release rates in simulated intestinal medium of AZT were demonstrated by in vitro release studies. The nanoparticles liquid uptake ability associated to the mucoadhesiveness by electronic interaction between the particles and mucus revealed that the drug delivery system developed in this work is a promising approach to improve the permeation of this drug throughout the intestinal mucosa.

  17. Combinatorial Approach of Antigen Delivery Using M Cell-Homing Peptide and Mucoadhesive Vehicle to Enhance the Efficacy of Oral Vaccine.

    PubMed

    Singh, Bijay; Maharjan, Sushila; Jiang, Tao; Kang, Sang-Kee; Choi, Yun-Jaie; Cho, Chong-Su

    2015-11-02

    Orally ingested pathogens or antigens are taken up by microfold cells (M cells) in Peyer's patches of intestine to initiate protective immunity against infections. However, the uptake of orally delivered protein antigens through M cells is very low due to lack of specificity of proteins toward M cells and degradation of proteins in the harsh environment of gastrointestinal (GI) tract. To overcome these limitations, here we developed a pH-sensitive and mucoadhesive vehicle of thiolated eudragit (TE) microparticles to transport an M cell-targeting peptide-fused model protein antigen. Particularly, TE prolonged the particles transit time through the GI tract and predominantly released the proteins in ileum where M cells are abundant. Thus, oral delivery of TE microparticulate antigens exhibited high transcytosis of antigens through M cells resulting in strong protective sIgA as well as systemic IgG antibody responses. Importantly, the delivery system not only induced CD4(+) T cell immune responses but also generated strong CD8(+) T cell responses with enhanced production of IFN-γ in spleen. Given that M cells are considered a promising target for oral vaccination, this study could provide a new combinatorial method for the development of M-cell-targeted mucosal vaccines.

  18. Immune response induced by conjunctival immunization with polymeric antigen BLSOmp31 using a thermoresponsive and mucoadhesive in situ gel as vaccine delivery system for prevention of ovine brucellosis.

    PubMed

    Díaz, Alejandra Graciela; Quinteros, Daniela Alejandra; Gutiérrez, Silvina Elena; Rivero, Mariana Alejandra; Palma, Santiago Daniel; Allemandi, Daniel Alberto; Pardo, Romina Paola; Zylberman, Vanesa; Goldbaum, Fernando Alberto; Estein, Silvia Marcela

    2016-10-01

    Control of ovine brucellosis with subcellular vaccines can solve some drawbacks associated with the use of Brucella melitensis Rev.1. Previous studies have demonstrated that the polymeric antigen BLSOmp31 administered by parenteral route was immunogenic and conferred significant protection against B. ovis in rams. Immunization with BLSOmp31 by conjunctival route could be efficient for the induction of mucosal and systemic immune responses. In this work, we evaluated the conjunctival immunization using a thermoresponsive and mucoadhesive in situ gel composed of Poloxamer 407 (P407) and chitosan (Ch) as vaccine delivery system for BLSOmp31 in rams. Serum samples, saliva, lacrimal, preputial and nasal secretions were analyzed to measure specific IgG and IgA antibodies. Cellular immune response was evaluated in vivo and in vitro. Immunization with BLSOmp31-P407-Ch induced high IgG antibody levels in serum and preputial secretions which remained at similar levels until the end of the experiment. Levels of IgG in saliva, lacrimal and nasal secretions were also higher compared to unvaccinated control group but decreased more rapidly. IgA antibodies were only detected in nasal and preputial secretions. BLSOmp31-P407-Ch stimulated a significant cellular immune response in vivo and in vitro. The induction of systemic and local immune responses indicates a promising potential of P407-Ch for the delivery of BLSOmp31 by conjunctival route.

  19. Design and development of nasal mucoadhesive microspheres containing tramadol HCl for CNS targeting.

    PubMed

    Belgamwar, Veena S; Patel, Hitesh S; Joshi, Ashwini S; Agrawal, Anshuman; Surana, Sanjay J; Tekade, Avinash R

    2011-07-01

    In the present study, tramadol HCl microspheres were designed in order to accomplish rapid delivery of drug to the brain. For this purpose, lower viscosity grade HPMC (E15) was chosen as mucoadhesive polymer and used at different drug/polymer ratios in the microspheres formulations. The spray-dried microspheres were evaluated with respect to the production yield, incorporation efficiency, particle size, mucoadhesive property, in vitro drug release, histopathological study, and radio imaging study in rabbits. DSC and XRD study showed molecular dispersion and conversion of the drug into amorphous form. Size and surface morphology of microspheres was analyzed by SEM and found to be spherical in shape with smooth surface. It was found that the particle size, swelling ability, and incorporation efficiency of microspheres increase with increasing drug-to-polymer ratio. Microspheres show adequate mucoadhesion and do not have any destructive effect on nasal mucosa. In vitro drug release of optimized formulation was found to be 94% after 90 min. The radio imaging study indicated localization of drug in the brain. Hence, tramadol HCl microspheres based on a HPMC E15 may be a promising nasal delivery system for CNS targeting.

  20. Intelligent hydrogels for drug delivery system.

    PubMed

    He, Liumin; Zuo, Qinhua; Xie, Shasha; Huang, Yuexin; Xue, Wei

    2011-09-01

    Intelligent hydrogel, also known as smart hydrogels, are materials with great potential for development in drug delivery system. Intelligent hydrogel also has the ability to perceive as a signal structure change and stimulation. The review introduces the temperature-, pH-, electric signal-, biochemical molecule-, light- and pressure- sensitive hydrogels. Finally, we described the application of intelligent hydrogel in drug delivery system and the recent patents involved for hydrogel in drug delivery.

  1. Novel central nervous system drug delivery systems.

    PubMed

    Stockwell, Jocelyn; Abdi, Nabiha; Lu, Xiaofan; Maheshwari, Oshin; Taghibiglou, Changiz

    2014-05-01

    For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases.

  2. Alginate Particles as Platform for Drug Delivery by the Oral Route: State-of-the-Art

    PubMed Central

    2014-01-01

    Pharmaceutical research and development aims to design products with ensured safety, quality, and efficacy to treat disease. To make the process more rational, coherent, efficient, and cost-effective, the field of Pharmaceutical Materials Science has emerged as the systematic study of the physicochemical properties and behavior of materials of pharmaceutical interest in relation to product performance. The oral route is the most patient preferred for drug administration. The presence of a mucus layer that covers the entire gastrointestinal tract has been exploited to expand the use of the oral route by developing a mucoadhesive drug delivery system that showed a prolonged residence time. Alginic acid and sodium and potassium alginates have emerged as one of the most extensively explored mucoadhesive biomaterials owing to very good cytocompatibility and biocompatibility, biodegradation, sol-gel transition properties, and chemical versatility that make possible further modifications to tailor their properties. The present review overviews the most relevant applications of alginate microparticles and nanoparticles for drug administration by the oral route and discusses the perspectives of this biomaterial in the future. PMID:25101184

  3. Breathable Medicine: Pulmonary Mode of Drug Delivery.

    PubMed

    Gandhimathi, Chinnasamy; Venugopal, Jayarama Reddy; Sundarrajan, Subramanian; Sridhar, Radhakrishnan; Tay, Samuel Sam Wah; Ramakrishna, Seeram; Kumar, Srinivasan Dinesh

    2015-04-01

    Pharmaceutically active compounds require different modes of drug delivery systems to accomplish therapeutic activity without loss of its activity and lead to exhibit no adverse effects. Originating from ancient days, pulmonary mode of drug delivery is gaining much importance compared to other modes of drug delivery systems with respect to specific diseases. Pulmonary drug delivery is a non-invasive route for local and systemic therapies together with more patient convenience, compliance and is a needleless system. In this review, we addressed the vaccine delivery via non- or minimally invasive routes. Polymeric nanoparticles are preferred for use in the pulmonary delivery devices owing to a prolonged retention in lungs. Small site for absorption, mucociliary clearance, short residence time and low bioavailability are some of the limitations in pulmonary drug delivery have been resolved by generating micro- and nano-sized aerosol particles. We have classified the breathable medicine on the basis of available devices for inhalation and also prominent diseases treated through pulmonary mode of drug delivery. Owing to increasing toxicity of pharmacological drugs, the use of natural medicines has been rapidly gaining importance recently. The review article describes breathability of medicines or the pulmonary mode of drug delivery system and their drug release profile, absorption, distribution and efficacy to cure asthma and diabetes.

  4. Magnetic Resonance-Guided Drug Delivery.

    PubMed

    Mikhail, Andrew S; Partanen, Ari; Yarmolenko, Pavel; Venkatesan, Aradhana M; Wood, Bradford J

    2015-11-01

    The use of clinical imaging modalities for the guidance of targeted drug delivery systems, known as image-guided drug delivery (IGDD), has emerged as a promising strategy for enhancing antitumor efficacy. MR imaging is particularly well suited for IGDD applications because of its ability to acquire images and quantitative measurements with high spatiotemporal resolution. The goal of IGDD strategies is to improve treatment outcomes by facilitating planning, real-time guidance, and personalization of pharmacologic interventions. This article reviews basic principles of targeted drug delivery and highlights the current status, emerging applications, and future paradigms of MR-guided drug delivery.

  5. Preparation and evaluation of glyceryl monooleate-coated hollow-bioadhesive microspheres for gastroretentive drug delivery.

    PubMed

    Liu, Yuanfen; Zhang, Jianjun; Gao, Yuan; Zhu, Jiabi

    2011-07-15

    The purpose of this study was to produce hollow and bioadhesive microspheres to lengthen drug retention time in the stomach. In these microspheres, ethylcellulose was used as the matrix, Eudragit EPO was employed to modulate the release rate, and glyceryl monooleate (GMO) was the bioadhesive polymer in situ. The morphological characteristics of the microspheres were defined using scanning electron microscopy. The in vitro release test showed that the release rate of drug from the microspheres was pH-dependent, and was not influenced by the GMO coating film. The prepared microspheres demonstrated strong mucoadhesive properties with good buoyancy both in vitro and in vivo. Pharmacokinetic analysis indicated that the elimination half-life time of the hollow-bioadhesive microspheres was prolonged, and that the elimination rate was decreased. In conclusion, the hollow-bioadhesive synergic drug delivery system may be advantageous in the treatment of stomach diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Collagen macromolecular drug delivery systems

    SciTech Connect

    Gilbert, D.L.

    1988-01-01

    The objective of this study was to examine collagen for use as a macromolecular drug delivery system by determining the mechanism of release through a matrix. Collagen membranes varying in porosity, crosslinking density, structure and crosslinker were fabricated. Collagen characterized by infrared spectroscopy and solution viscosity was determined to be pure and native. The collagen membranes were determined to possess native vs. non-native quaternary structure and porous vs. dense aggregate membranes by electron microscopy. Collagen monolithic devices containing a model macromolecule (inulin) were fabricated. In vitro release rates were found to be linear with respect to t{sup {1/2}} and were affected by crosslinking density, crosslinker and structure. The biodegradation of the collagen matrix was also examined. In vivo biocompatibility, degradation and {sup 14}C-inulin release rates were evaluated subcutaneously in rats.

  7. Drug delivery systems: An updated review

    PubMed Central

    Tiwari, Gaurav; Tiwari, Ruchi; Sriwastawa, Birendra; Bhati, L; Pandey, S; Pandey, P; Bannerjee, Saurabh K

    2012-01-01

    Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. For the treatment of human diseases, nasal and pulmonary routes of drug delivery are gaining increasing importance. These routes provide promising alternatives to parenteral drug delivery particularly for peptide and protein therapeutics. For this purpose, several drug delivery systems have been formulated and are being investigated for nasal and pulmonary delivery. These include liposomes, proliposomes, microspheres, gels, prodrugs, cyclodextrins, among others. Nanoparticles composed of biodegradable polymers show assurance in fulfilling the stringent requirements placed on these delivery systems, such as ability to be transferred into an aerosol, stability against forces generated during aerosolization, biocompatibility, targeting of specific sites or cell populations in the lung, release of the drug in a predetermined manner, and degradation within an acceptable period of time. PMID:23071954

  8. Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery

    PubMed Central

    Ahmed, Tarek A; Aljaeid, Bader M

    2016-01-01

    Naturally occurring polymers, particularly of the polysaccharide type, have been used pharmaceutically for the delivery of a wide variety of therapeutic agents. Chitosan, the second abundant naturally occurring polysaccharide next to cellulose, is a biocompatible and biodegradable mucoadhesive polymer that has been extensively used in the preparation of micro-as well as nanoparticles. The prepared particles have been exploited as a potential carrier for different therapeutic agents such as peptides, proteins, vaccines, DNA, and drugs for parenteral and nonparenteral administration. Therapeutic agent-loaded chitosan micro- or nanoparticles were found to be more stable, permeable, and bioactive. In this review, we are highlighting the different methods of preparation and characterization of chitosan micro- and nanoparticles, while reviewing the pharmaceutical applications of these particles in drug delivery. Moreover, the roles of chitosan derivatives and chitosan metal nanoparticles in drug delivery have been illustrated. PMID:26869768

  9. Design and In Vitro/In Vivo Evaluation of Ultra-Thin Mucoadhesive Buccal Film Containing Fluticasone Propionate.

    PubMed

    Ammar, Hussein O; Ghorab, Mahmoud M; Mahmoud, Azza A; Shahin, Hend I

    2017-01-01

    Fluticasone propionate is a synthetic corticosteroid drug distinguished by its potent anti-inflammatory action with low systemic side effects in comparison to other corticosteroids making it a potential drug for local buccal delivery. The aim of the present study was to design mucoadhesive buccal film containing fluticasone that is aesthetically acceptable and could maintain local drug release for a sustained period to manage the sign and symptoms of severe erosive mouth lesions. Solvent casting technique was used in film preparation. Different polymeric blends were used either alone or in combination with mucoadhesive polymers, sodium carboxymethyl cellulose (SCMC), or Carbopol 971P at different concentrations. The physicochemical properties, in vitro mucoadhesion time as well as the drug release properties for all prepared formulations were determined. Selected formulations with adequate properties were further examined by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) and subjected to in vivo evaluation. Films containing hydroxypropyl methylcellulose (HPMC)/ethyl cellulose (EC) showed acceptable physicochemical properties, homogenous drug distribution, convenient mucoadhesion time, moderate swelling as well as sustained drug release up to 12 h. The biological performance of these formulations was assessed on healthy human volunteers and compared with a prepared mouthwash which showed enhanced pharmacokinetic parameters for the selected films in comparison to the mouthwash. The results revealed that the optimized formulation containing HPMC/EC and 10% SCMC could successfully achieve sustained drug release for 10 h which is considered promising for local treatment of severe mouth lesions.

  10. Optimal stent design for drug delivery.

    PubMed

    Rogers, Campbell D K

    2004-01-01

    The efficacy and safety of drug-eluting coronary stents might differ depending on the pharmacologic agents and stent delivery systems used. Recent research has focused on the various constituents of drug-delivery stents, including the stent backbone, materials used as drug-delivery vehicles, and the physicochemical properties of the pharmacotherapeutic agents themselves. Metal stents coated with an outer layer of polymer (bioabsorbable or non-bioabsorbable) can be drug-loaded, thus providing more controlled and sustained drug delivery and allowing more optimal drug-tissue interactions. Among the next generation of drug-eluting stents will be a stent that uses the non-bioabsorbable polymer phosphorylcholine to release the sirolimus analogue ABT-578; another stent will use a highly deliverable cobalt-chromium metal alloy stent platform and, for the first time, a bioabsorbable polymeric coating (thin-film polylactic acid) for drug encapsulation and release.

  11. Refilling drug delivery depots through the blood.

    PubMed

    Brudno, Yevgeny; Silva, Eduardo A; Kearney, Cathal J; Lewin, Sarah A; Miller, Alex; Martinick, Kathleen D; Aizenberg, Michael; Mooney, David J

    2014-09-02

    Local drug delivery depots have significant clinical utility, but there is currently no noninvasive technique to refill these systems once their payload is exhausted. Inspired by the ability of nanotherapeutics to target specific tissues, we hypothesized that blood-borne drug payloads could be modified to home to and refill hydrogel drug delivery systems. To address this possibility, hydrogels were modified with oligodeoxynucleotides (ODNs) that provide a target for drug payloads in the form of free alginate strands carrying complementary ODNs. Coupling ODNs to alginate strands led to specific binding to complementary-ODN-carrying alginate gels in vitro and to injected gels in vivo. When coupled to a drug payload, sequence-targeted refilling of a delivery depot consisting of intratumor hydrogels completely abrogated tumor growth. These results suggest a new paradigm for nanotherapeutic drug delivery, and this concept is expected to have applications in refilling drug depots in cancer therapy, wound healing, and drug-eluting vascular grafts and stents.

  12. Development of an ANN optimized mucoadhesive buccal tablet containing flurbiprofen and lidocaine for dental pain.

    PubMed

    Hussain, Amjad; Syed, Muhammad Ali; Abbas, Nasir; Hanif, Sana; Arshad, Muhammad Sohail; Bukhari, Nadeem Irfan; Hussain, Khalid; Akhlaq, Muhammad; Ahmad, Zeeshan

    2016-06-01

    A novel mucoadhesive buccal tablet containing flurbiprofen (FLB) and lidocaine HCl (LID) was prepared to relieve dental pain. Tablet formulations (F1-F9) were prepared using variable quantities of mucoadhesive agents, hydroxypropyl methyl cellulose (HPMC) and sodium alginate (SA). The formulations were evaluated for their physicochemical properties, mucoadhesive strength and mucoadhesion time, swellability index and in vitro release of active agents. Release of both drugs depended on the relative ratio of HPMC:SA. However, mucoadhesive strength and mucoadhesion time were better in formulations, containing higher proportions of HPMC compared to SA. An artificial neural network (ANN) approach was applied to optimise formulations based on known effective parameters (i.e., mucoadhesive strength, mucoadhesion time and drug release), which proved valuable. This study indicates that an effective buccal tablet formulation of flurbiprofen and lidocaine can be prepared via an optimized ANN approach.

  13. Implantable Devices for Sustained, Intravesical Drug Delivery

    PubMed Central

    2016-01-01

    In clinical settings, intravesical instillation of a drug bolus is often performed for the treatment of bladder diseases. However, it requires repeated instillations to extend drug efficacy, which may result in poor patient compliance. To alleviate this challenge, implantable devices have been developed for the purpose of sustained, intravesical drug delivery. In this review, we briefly summarize the current trend in the development of intravesical drug-delivery devices. We also introduce the most recently developed devices with strong potential for intravesical drug-delivery applications. PMID:27377941

  14. Mucoadhesive and pH-sensitive thiolated Eudragit microspheres for oral delivery of Pasteurella multocida antigens containing dermonecrotoxin.

    PubMed

    Islam, Mohammad Ariful; Jiang, Hu-Lin; Quan, Ji-Shan; Arote, Rohidas B; Kang, Mi-Lan; Yoo, Han-Sang; Yun, Cheol-Heui; Choi, Yun-Jaie; Cho, Chong-Su

    2011-05-01

    In this study, cysteine was conjugated to the Eudragit to have mucoadhesive and pH-sensitive properties. Pasteurella multocida dermonecrotoxin (PMT) is a major virulence factor as a causative agent of atrophic rhinitis (AR) in swine and, therefore, inactivated P. multocida was used as a candidate vaccine in the current study. PMT-loaded thiolated Eudragit microspheres (TEMS) prepared using W/O/W emulsion-solvent evaporation method were characterized to assess their efficacy in oral vaccination. PMT-loaded TEMS were observed as spherical shapes with smooth surfaces and average particle sizes were 5.2 +/- 0.55 microm. The loading efficiency of PMT in the TEMS was about 75.3%. A significantly higher percentage of PMT from PMT-loaded TEMS was released at pH 7.4 than at pH 1.5. Murine macrophage stimulated with PMT-loaded TEMS facilitated a gradual secretion of tumor necrosis factor-alpha and nitric oxide as immune stimulatory mediators in a time dependent manner, suggesting that the released PMT from PMT-loaded TEMS had immune stimulating activity of AR vaccine in vitro.

  15. Permeation enhancer strategies in transdermal drug delivery.

    PubMed

    Marwah, Harneet; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    Today, ∼74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system.

  16. Prodrug Strategies in Ocular Drug Delivery

    PubMed Central

    Barot, Megha; Bagui, Mahuya; Gokulgandhi, Mitan R.; Mitra, Ashim K.

    2015-01-01

    Poor bioavailability of topically instilled drug is the major concern in the field of ocular drug delivery. Efflux transporters, static and dynamic ocular barriers often possess rate limiting factors for ocular drug therapy. Different formulation strategies like suspension, ointment, gels, nanoparticles, implants, dendrimers and liposomes have been employed in order to improve drug permeation and retention by evading rate limiting factors at the site of absorption. Chemical modification such as prodrug targeting various nutrient transporters (amino acids, peptide and vitamin) has evolved a great deal ofintereSt to improve ocular drug delivery. In this review, we have discussed various prodrug strategies which have been widely applied for enhancing therapeutic efficacy of ophthalmic drugs. The purpose of this review is to provide an update on the utilization of prodrug concept in ocular drug delivery. In addition, this review will highlight ongoing academic and industrial research and development in terms of ocular prodrug design and delivery. PMID:22530907

  17. Nanoparticles for intracellular-targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Paulo, Cristiana S. O.; Pires das Neves, Ricardo; Ferreira, Lino S.

    2011-12-01

    Nanoparticles (NPs) are very promising for the intracellular delivery of anticancer and immunomodulatory drugs, stem cell differentiation biomolecules and cell activity modulators. Although initial studies in the area of intracellular drug delivery have been performed in the delivery of DNA, there is an increasing interest in the use of other molecules to modulate cell activity. Herein, we review the latest advances in the intracellular-targeted delivery of short interference RNA, proteins and small molecules using NPs. In most cases, the drugs act at different cellular organelles and therefore the drug-containing NPs should be directed to precise locations within the cell. This will lead to the desired magnitude and duration of the drug effects. The spatial control in the intracellular delivery might open new avenues to modulate cell activity while avoiding side-effects.

  18. Microneedles: an emerging transdermal drug delivery system.

    PubMed

    Bariya, Shital H; Gohel, Mukesh C; Mehta, Tejal A; Sharma, Om Prakash

    2012-01-01

    One of the thrust areas in drug delivery research is transdermal drug delivery systems (TDDS) due to their characteristic advantages over oral and parenteral drug delivery systems. Researchers have focused their attention on the use of microneedles to overcome the barrier of the stratum corneum. Microneedles deliver the drug into the epidermis without disruption of nerve endings. Recent advances in the development of microneedles are discussed in this review for the benefit of young scientists and to promote research in the area. Microneedles are fabricated using a microelectromechanical system employing silicon, metals, polymers or polysaccharides. Solid coated microneedles can be used to pierce the superficial skin layer followed by delivery of the drug. Advances in microneedle research led to development of dissolvable/degradable and hollow microneedles to deliver drugs at a higher dose and to engineer drug release. Iontophoresis, sonophoresis and electrophoresis can be used to modify drug delivery when used in concern with hollow microneedles. Microneedles can be used to deliver macromolecules such as insulin, growth hormones, immunobiologicals, proteins and peptides. Microneedles containing 'cosmeceuticals' are currently available to treat acne, pigmentation, scars and wrinkles, as well as for skin tone improvement. Literature survey and patents filled revealed that microneedle-based drug delivery system can be explored as a potential tool for the delivery of a variety of macromolecules that are not effectively delivered by conventional transdermal techniques. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

  19. [Site-specific drug delivery systems. I. Colon targeted delivery].

    PubMed

    Szente, Virág; Zelkó, Romána

    2007-01-01

    Colon specific drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon like Chron's disease, ulcerative colitis, irritable bowel syndrome, cancer or infections, but also for the potential it holds for the systemic delivery of proteins (e.g. insulin) and therapeutic peptides. These systems enable the protection of healthy tissues from the side effects of drugs and the drug intake of targeted cells, as well. The formulation of colon specific drug delivery systems is of great impact in the case of diseases having circadian rhythm (midnight gerd). Such circadian rhythm release drug delivery systems are designed to provide a plasma concentration--time profile, which varies according to physiological need at different times during the dosing period, i.e., mimicking the circadian rhythm and severity/manifestation of gastric acid secretion (and/or midnight gerd). In general four primary approaches have been proposed for colon targeted delivery namely pH-dependent systems, time dependent systems, colonic microflora activated systems and prodrugs.

  20. Mechanisms Underlying Drug Delivery to Peripheral Arteries.

    PubMed

    Li, Jun; Tzafriri, Rami; Patel, Sandeep M; Parikh, Sahil A

    2017-04-01

    Delivery of drugs onto arterial targets via endovascular devices commands several principles: dissolution, diffusion, convection, drug binding, barriers to absorption, and interaction between the drug, delivery vehicle, and accepting arterial wall. The understanding of drug delivery in the coronary vasculature is vast; there is ongoing work needed in the peripheral arteries. There are differences that account for some failures of application of coronary technology into the peripheral vascular space. Breakthroughs in peripheral vascular interventional techniques building on current technologies require investigators willing to acknowledge the similarities and differences between these different vascular territories, while developing technologies adapted for peripheral arteries.

  1. Preformulation studies and optimization of sodium alginate based floating drug delivery system for eradication of Helicobacter pylori.

    PubMed

    Diós, Péter; Nagy, Sándor; Pál, Szilárd; Pernecker, Tivadar; Kocsis, Béla; Budán, Ferenc; Horváth, Ildikó; Szigeti, Krisztián; Bölcskei, Kata; Máthé, Domokos; Dévay, Attila

    2015-10-01

    The aim of this study was to design a local, floating, mucoadhesive drug delivery system containing metronidazole for Helicobacter pylori eradication. Face-centered central composite design (with three factors, in three levels) was used for evaluation and optimization of in vitro floating and dissolution studies. Sodium alginate (X1), low substituted hydroxypropyl cellulose (L-HPC B1, X2) and sodium bicarbonate (X3) concentrations were the independent variables in the development of effervescent floating tablets. All tablets showed acceptable physicochemical properties. Statistical analysis revealed that tablets with 5.00% sodium alginate, 38.63% L-HPC B1 and 8.45% sodium bicarbonate content showed promising in vitro floating and dissolution properties for further examinations. Optimized floating tablets expressed remarkable floating force. Their in vitro dissolution studies were compared with two commercially available non-floating metronidazole products and then microbiologically detected dissolution, ex vivo detachment force, rheological mucoadhesion studies and compatibility studies were carried out. Remarkable similarity (f1, f2) between in vitro spectrophotometrically and microbiologically detected dissolutions was found. Studies revealed significant ex vivo mucoadhesion of optimized tablets, which was considerably increased by L-HPC. In vivo X-ray CT studies of optimized tablets showed 8h gastroretention in rats represented by an animation prepared by special CT technique. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Polysaccharides in colon-specific drug delivery.

    PubMed

    Sinha, V R; Kumria, R

    2001-08-14

    Natural polysaccharides are now extensively used for the development of solid dosage forms for delivery of drug to the colon. The rationale for the development of a polysaccharide based delivery system for colon is the presence of large amounts of polysaccharidases in the human colon as the colon is inhabited by a large number and variety of bacteria which secrete many enzymes e.g. beta-D-glucosidase, beta-D-galactosidase, amylase, pectinase, xylanase, beta-D-xylosidase, dextranase, etc. Various major approaches utilizing polysaccharides for colon-specific delivery are fermentable coating of the drug core, embedding of the drug in biodegradable matrix, formulation of drug-saccharide conjugate (prodrugs). A large number of polysaccharides have already been studied for their potential as colon-specific drug carrier systems, such as chitosan, pectin, chondroitin sulphate, cyclodextrin, dextrans, guar gum, inulin, amylose and locust bean gum. Recent efforts and approaches exploiting these polysaccharides in colon-specific drug delivery are discussed.

  3. Colloidal microgels in drug delivery applications

    PubMed Central

    Vinogradov, Serguei V.

    2005-01-01

    Colloidal microgels have recently received attention as environmentally responsive systems and now are increasingly used in applications as carriers for therapeutic drugs and diagnostic agents. Synthetic microgels consist of a crosslinked polymer network that provides a depot for loaded drugs, protection against environmental hazards and template for post-synthetic modification or vectorization of the drug carriers. The aim of this manuscript is to review recent attempts to develop new microgel formulations for oral drug delivery, to design metal-containing microgels for diagnostic and therapeutic applications, and to advance approaches including the systemic administration of microgels. Novel nanogel drug delivery systems developed in the authors’ laboratory are discussed in details including aspects of their synthesis, vectorization and recent applications for encapsulation of low molecular weight drugs or formulation of biological macromolecules. The findings reviewed here are encouraging for further development of the nanogels as intelligent drug carriers with such features as targeted delivery and triggered drug release. PMID:17168773

  4. Intravenous drug delivery in neonates: lessons learnt.

    PubMed

    Sherwin, Catherine M T; Medlicott, Natalie J; Reith, David M; Broadbent, Roland S

    2014-06-01

    Intravenous drug administration presents a series of challenges that relate to the pathophysiology of the neonate and intravenous infusion systems in neonates. These challenges arise from slow intravenous flow rates, small drug volume, dead space volume and limitations on the flush volume in neonates. While there is a reasonable understanding of newborn pharmacokinetics, an appreciation of the substantial delay and variability in the rate of drug delivery from the intravenous line is often lacking. This can lead to difficulties in accurately determining the pharmacokinetic and pharmacodynamic relationship of drugs in the smallest patients. The physical variables that affect the passage of drugs through neonatal lines need to be further explored in order to improve our understanding of their impact on the delivery of drugs by this route in neonates. Through careful investigation, the underlying causes of delayed drug delivery may be identified and administration protocols can then be modified to ensure predictable, appropriate drug input kinetics.

  5. Formulation and evaluation of floating mucoadhesive alginate beads for targeting Helicobacter pylori.

    PubMed

    Adebisi, Adeola O; Laity, Peter R; Conway, Barbara R

    2015-04-01

    There are various obstacles in the eradication of Helicobacter pylori infections, including low antibiotic levels and poor accessibility of the drug at the site of the infection. This study describes the preparation and characterisation of novel floating mucoadhesive alginate beads loaded with clarithromycin for delivery to the gastric mucosa to improve the eradication of this microorganism. Calcium alginate beads were prepared by ionotropic gelation. The formulation was modified through addition of oil and coating with chitosan to improve floating, mucoadhesion and modify drug release. Scanning electron microscopy confirmed the sphericity of the beads with X-ray microtomography showing the three-dimensional structure of the beads with the layered internal structure of the bead and the even distribution of the drug within the bead. This formulation combined two gastro-retentive strategies, and produced excellent in-vitro floating, mucoadhesive and drug release characteristics. Enhanced stability of the beads in phosphate buffer raises a potential for the modified formulations to be targeted to regions of higher pH within the gastrointestinal tract. Drug release from these beads was sustained through an unstirred mucin layer simulating in-vivo conditions under which the H. pylori resides in the gastric mucosa. This novel formulation will ensure retention for a longer period in the stomach than conventional formulations and control drug release, ensuring high local drug concentrations, leading to improved eradication of the bacteria. © 2014 Royal Pharmaceutical Society.

  6. Nanomedicine and drug delivery: a mini review

    NASA Astrophysics Data System (ADS)

    Mirza, Agha Zeeshan; Siddiqui, Farhan Ahmed

    2014-02-01

    The field of nanotechnology now has pivotal roles in electronics, biology and medicine. Its application can be appraised, as it involves the materials to be designed at atomic and molecular level. Due to the advantage of their size, nanospheres have been shown to be robust drug delivery systems and may be useful for encapsulating drugs and enabling more precise targeting with a controlled release. In this review specifically, we highlight the recent advances of this technology for medicine and drug delivery systems.

  7. Magnetic nanoparticles for gene and drug delivery

    PubMed Central

    McBain, Stuart C; Yiu, Humphrey HP; Dobson, Jon

    2008-01-01

    Investigations of magnetic micro- and nanoparticles for targeted drug delivery began over 30 years ago. Since that time, major progress has been made in particle design and synthesis techniques, however, very few clinical trials have taken place. Here we review advances in magnetic nanoparticle design, in vitro and animal experiments with magnetic nanoparticle-based drug and gene delivery, and clinical trials of drug targeting. PMID:18686777

  8. Synthetic Lipoproteins as Carriers for Drug Delivery.

    PubMed

    Huang, Gangliang; Liu, Yang; Huang, Hualiang

    2016-01-01

    Synthetic lipoprotein is an effective carrier of targeted delivery for drugs. It has the very small size, good biocompatibility, suitable half-life, and specific lipoprotein receptorbinding capacity. Compared with the traditional natural lipoprotein, synthetic lipoprotein not only retains the original biological characteristics and functions, but also exhibits the excellent characteristics in drug delivery. Herein, the advantages, development, applications, and prospect of synthetic lipoproteins as drug carriers were summarized.

  9. Insulin availability from mucoadhesive tablets.

    PubMed

    Pluta, J; Haznar, D; Suszka-Switek, A; Ryszka, F

    2008-09-01

    The widespread implementation of peptides as drugs encounters numerous obstacles, the main being invasive and inconvenient parenteral administration. Oral transmucosal administration is one of the possible alternatives, valuable for its noninvasiveness and easy accessibility. The aim of our study was to determine the implementation possibilities of mucoadhesive tablets prepared on a methylcellulose and sodium alginate basis with an addition of absorption-modifying hyaluronic acid, as carriers for peptides destined for oral transmucosal administration. Two series of 50 mg tablets containing 5mg of insulin were prepared for the study. The first series contained methylcellulose, hyaluronic acid and mannitol, while the second series' formulation included sodium alginate, hyaluronic acid and mannitol. Carried out study confirmed that insulin administration in the form of mucoadhesive tablets lowers blood glucose levels in rabbits. Better effects were reached in vivo in the case of MC-based tablets, for which stronger and longer glycemia lowering was achieved.

  10. Inorganic Nanomaterials as Carriers for Drug Delivery.

    PubMed

    Chen, Shizhu; Hao, Xiaohong; Liang, Xingjie; Zhang, Qun; Zhang, Cuimiao; Zhou, Guoqiang; Shen, Shigang; Jia, Guang; Zhang, Jinchao

    2016-01-01

    For safe and effective therapy, drugs must be delivered efficiently and with minimal systemic side effects. Nanostructured drug carriers enable the delivery of small-molecule drugs as well as nucleic acids and proteins. Inorganic nanomaterials are ideal for drug delivery platforms due to their unique physicochemical properties, such as facile preparation, good storage stability and biocompatibility. Many inorganic nanostructure-based drug delivery platforms have been prepared. Although there are still many obstacles to overcome, significant advances have been made in recent years. This review focuses on the status and development of inorganic nanostructures, including silica, quantum dots, gold, carbon-based and magnetic iron oxide-based nanostructures, as carriers for chemical and biological drugs. We specifically highlight the extensive use of these inorganic drug carriers for cancer therapy. Finally, we discuss the most important areas in the field that urgently require further study.

  11. Preparation of ibuprofen-loaded chitosan films for oral mucosal drug delivery using supercritical solution impregnation.

    PubMed

    Tang, Chuan; Guan, Yi-Xin; Yao, Shan-Jing; Zhu, Zi-Qiang

    2014-10-01

    Drug-loaded chitosan films suitable for oral mucosal drug delivery were prepared using supercritical solution impregnation (SSI) technology. Firstly, chitosan films were obtained via casting method, and the film properties including water-uptake, erosion and mucoadhesive were characterized. SSI process was then employed to load the drug of ibuprofen onto the prepared chitosan films, and the effects of impregnation pressure and temperature on morphologies of the ibuprofen-loaded chitosan films and drug loading capacity (DLC) were studied. The SEM and X-ray diffraction patterns suggested that distinct ibuprofen shapes such as microparticles, flake, rod-like and needle-like occurred after impregnation at different pressures, and DLC varied from 7.9% to 130.4% during the SSI process. The ex vivo release profiles showed that ibuprofen-loaded chitosan films could deliver the drug across the rabbit buccal mucosa, and up to 70% of the ibuprofen was released from the matrix in 460 min. SSI process is a promising method to prepare drug-loaded film formulations for oral mucosal drug delivery, which provides the advantages of low solvent residual and sustained- and controlled- release behavior.

  12. Mucosal drug delivery: membranes, methodologies, and applications.

    PubMed

    Song, Yifan; Wang, Yiping; Thakur, Rashmi; Meidan, Victor M; Michniak, Bozena

    2004-01-01

    In recent years, extensive research into novel forms of drug delivery has suggested that mucosal approaches offer a promising therapeutic alternative, especially for systemically acting drugs. Transmucosal drug delivery offers many benefits, including noninvasive administration, convenience, rapid onset, as well as elimination of hepatic first-pass metabolism. The investigated absorptive surfaces consist of the nasal, buccal, ocular, vaginal, and rectal mucosae. Among these, the nasal and buccal routes have proved the most promising to date. The bioavailability achieved mainly depends upon the pathophysiological state of the mucosa and the properties of both the drug and delivery systems. Various agents can increase the efficacy of transmucosal drug delivery. These include cyclodextrins, bile salts, surfactants, fusidic acid derivatives, microspheres, liposomes, and bioadhesive agents. The mechanisms of action, effectiveness, and toxicity profiles of these enhancers have been investigated extensively in both animal and human models.

  13. Radiation sterilization of new drug delivery systems

    PubMed Central

    Abuhanoğlu, Gürhan

    2014-01-01

    Radiation sterilization has now become a commonly used method for sterilization of several active ingredients in drugs or drug delivery systems containing these substances. In this context, many applications have been performed on the human products that are required to be sterile, as well as on pharmaceutical products prepared to be developed. The new drug delivery systems designed to deliver the medication to the target tissue or organ, such as microspheres, nanospheres, microemulsion, and liposomal systems, have been sterilized by gamma (γ) and beta (β) rays, and more recently, by e-beam sterilization. In this review, the sterilization of new drug delivery systems was discussed other than conventional drug delivery systems by γ irradiation. PMID:24936306

  14. Radiation sterilization of new drug delivery systems.

    PubMed

    Abuhanoğlu, Gürhan; Ozer, A Yekta

    2014-06-01

    Radiation sterilization has now become a commonly used method for sterilization of several active ingredients in drugs or drug delivery systems containing these substances. In this context, many applications have been performed on the human products that are required to be sterile, as well as on pharmaceutical products prepared to be developed. The new drug delivery systems designed to deliver the medication to the target tissue or organ, such as microspheres, nanospheres, microemulsion, and liposomal systems, have been sterilized by gamma (γ) and beta (β) rays, and more recently, by e-beam sterilization. In this review, the sterilization of new drug delivery systems was discussed other than conventional drug delivery systems by γ irradiation.

  15. Polypeptides and polyaminoacids in drug delivery.

    PubMed

    González-Aramundiz, José Vicente; Lozano, María Victoria; Sousa-Herves, Ana; Fernandez-Megia, Eduardo; Csaba, Noemi

    2012-02-01

    Advances achieved over the last few years in drug delivery have provided novel and versatile possibilities for the treatment of various diseases. Among the biomaterials applied in this field, it is worth highlighting the increasing importance of polyaminoacids and polypeptides. The appealing properties of these polymers are very promising for the design of novel compositions in a variety of drug delivery applications. This review provides an overview on the general characteristics of polyaminoacids and polypeptides and briefly discusses different synthetic pathways for their production. This is followed by a detailed description of different drug delivery applications of these polymers, emphasizing those examples that already reached advanced preclinical development or have entered clinical trials. Polyaminoacids and polypeptides are gaining much attention in drug delivery due to their exceptional properties. Their application as polymers for drug delivery purposes has been sped up by the significant achievements related to their synthesis. Certainly, cancer therapy has benefited the most from these advances, although other fields such as vaccine delivery and alternative administration routes are also being successfully explored. The design of new entities based on polyaminoacids and polypeptides and the improved insight gained in drug delivery guarantee exciting findings in the near future.

  16. Interactions of mussel-inspired polymeric nanoparticles with gastric mucin: Implications for gastro-retentive drug delivery.

    PubMed

    Sunoqrot, Suhair; Hasan, Lina; Alsadi, Aya; Hamed, Rania; Tarawneh, Ola

    2017-08-01

    Mussel-inspired polydopamine (pD) coatings have several unique characteristics such as durability, versatility, and robustness. In this study, we have designed pD-coated nanoparticles (NPs) of methoxy polyethylene glycol-b-poly(ε-caprolactone) (mPEG-PCL@pD) as prospective nanoscale mucoadhesive platforms for gastro-retentive drug delivery. Successful pD coating on the NPs was confirmed by Transmission Electron Microscopy and X-ray Photoelectron Spectroscopy. Mucoadhesion of pD-coated NPs was investigated in vitro using commercially available mucin under stomach lumen-mimetic conditions. Mucin-NP interactions were monitored by dynamic light scattering, which showed a significant change in particle size distribution of pD-coated NPs at mucin/NP ratios of 1:1, 1:2, and 1:4w/w. Turbidity measurements indicated the formation of large mucin-NP aggregates causing a significant increase in turbidity at mucin/NP ratios of 2:1 and 4:1w/w. pD-coated NPs exhibited a significantly higher mucin adsorption ability compared to uncoated NPs at mucin/NP ratios of 1:4, 1:2, and 1:1w/w. Zeta potential measurements demonstrated that mucin-pD-coated NP interactions were not electrostatic in nature. An ex vivo wash-off test conducted using excised sheep stomach revealed that 78% of pD-coated NPs remained attached to the mucosa after 8h of incubation, compared to only 33% of uncoated NPs. In vitro release of rifampicin, used as a model drug, showed a similar controlled release profile from both pD-coated and uncoated NPs. Our results serve to expand the versatility of mussel-inspired coatings to the design of mucoadhesive nanoscale vehicles for oral drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Protein-Based Drug-Delivery Materials

    PubMed Central

    Jao, Dave; Xue, Ye; Medina, Jethro; Hu, Xiao

    2017-01-01

    There is a pressing need for long-term, controlled drug release for sustained treatment of chronic or persistent medical conditions and diseases. Guided drug delivery is difficult because therapeutic compounds need to survive numerous transport barriers and binding targets throughout the body. Nanoscale protein-based polymers are increasingly used for drug and vaccine delivery to cross these biological barriers and through blood circulation to their molecular site of action. Protein-based polymers compared to synthetic polymers have the advantages of good biocompatibility, biodegradability, environmental sustainability, cost effectiveness and availability. This review addresses the sources of protein-based polymers, compares the similarity and differences, and highlights characteristic properties and functionality of these protein materials for sustained and controlled drug release. Targeted drug delivery using highly functional multicomponent protein composites to guide active drugs to the site of interest will also be discussed. A systematical elucidation of drug-delivery efficiency in the case of molecular weight, particle size, shape, morphology, and porosity of materials will then be demonstrated to achieve increased drug absorption. Finally, several important biomedical applications of protein-based materials with drug-delivery function—including bone healing, antibiotic release, wound healing, and corneal regeneration, as well as diabetes, neuroinflammation and cancer treatments—are summarized at the end of this review. PMID:28772877

  18. Perspectives on transdermal ultrasound mediated drug delivery

    PubMed Central

    Smith, Nadine Barrie

    2007-01-01

    The use of needles for multiple injection of drugs, such as insulin for diabetes, can be painful. As a result, prescribed drug noncompliance can result in severe medical complications. Several noninvasive methods exist for transdermal drug delivery. These include chemical mediation using liposomes and chemical enhancers or physical mechanisms such as microneedles, iontophoresis, electroporation, and ultrasound. Ultrasound enhanced transdermal drug delivery offers advantages over traditional drug delivery methods which are often invasive and painful. A broad review of the transdermal ultrasound drug delivery literature has shown that this technology offers promising potential for noninvasive drug administration. From a clinical perspective, few drugs, proteins or peptides have been successfully administered transdermally because of the low skin permeability to these relatively large molecules, although much work is underway to resolve this problem. The proposed mechanism of ultrasound has been suggested to be the result of cavitation, which is discussed along with the bioeffects from therapeutic ultrasound. For low frequencies, potential transducers which can be used for drug delivery are discussed, along with cautions regarding ultrasound safety versus efficacy. PMID:18203426

  19. Atomization of denatured whey proteins as a novel and simple way to improve oral drug delivery system properties.

    PubMed

    Hsein, Hassana; Garrait, Ghislain; Mumin, Muhammad Ashraful; Beyssac, Eric; Hoffart, Valérie

    2017-07-18

    In the sphere of drug delivery, denatured whey protein (DWP) has in recent times gained press. However, to date, no scalable and affordable dosage form has been developed. The objective of our study was to evaluate the potential use of spray-dried DWP as a ready to use excipient for oral drug delivery. Therefore, solid state, FTIR spectra and wettability were studied. Dissolution, mucoadhesion and the effect on paracellular permeability were also evaluated. The spray-dried DWP particles were spherical with 4μm mean diameter. Further, relative to native WP, the spray-dried DWP particles bore reduced wettability, and their structure was characterized by the exposure of a high amount of free thiol and by the formation of intermolecular β-sheets. The DWP powders were mucoadhesive, enzymatic inhibitors, biocompatible and they induced the opening of tight junctions. Our study shows great potential for the use of spray-drying as a technique to modify the dissolution rate of drugs and enhance the oral bioavailability of molecules. That is, the use of spray drying as a single step ready to use DWP excipient. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Determination of ofloxacin in tear by HPLC-ESI-MS/MS method: comparison of ophthalmic drug release between a new mucoadhesive chitosan films and a conventional eye drop formulation in rabbit model.

    PubMed

    Byrro, Ricardo Martins Duarte; de Oliveira Fulgêncio, Gustavo; da Silva Cunha, Armando; César, Isabela Costa; Chellini, Paula Rocha; Pianetti, Gerson Antônio

    2012-11-01

    Ofloxacin, second-generation fluoroquinolone derivative, is one of the most commonly used to treat and prevent superficial ocular infection in animals and human beings. However, poor bioavailability, rapid elimination, and non compliance by patients are several problems associated with ocular route. Ophthalmic controlled drug delivery offers the potential to enhance the efficacy of treatment for pathological conditions, while reducing the side effects and the toxicity associated with frequent applications. Specific analytical methods to determine drugs in eye are needed to analyze and compare the new controlled release ocular devices with those conventional eye drops. The topical eye administration of ophthalmic drugs induces lachrymation, and the tear promotes a drug wash out. Quantify drugs in tear is a good tool to study their kinetic comportment in the eye. A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for quantitation of ofloxacin in rabbits' tears was developed and validated. The tear was collected with tear strips, extracted by a liquid extraction procedure and then separated on an ACE C(18) column with a mobile phase composed of 0.15% aqueous formic acid and methanol (60:40, v/v). Calibration curve was constructed over the range of 10-5000 ng/mL for ofloxacin. The mean R.S.D. values for the intra-run and inter-run precision were 5.15% and 4.35%, respectively. The mean accuracy value was 100.16%. The validated method was successfully applied to determine the ofloxacin concentration in tears of rabbits treated with a mucoadhesive chitosan films and a conventional eye drop formulation. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Thiomers: a new generation of mucoadhesive polymers.

    PubMed

    Bernkop-Schnürch, Andreas

    2005-11-03

    Thiolated polymers or designated thiomers are mucoadhesive basis polymers, which display thiol bearing side chains. Based on thiol/disulfide exchange reactions and/or a simple oxidation process disulfide bonds are formed between such polymers and cysteine-rich subdomains of mucus glycoproteins building up the mucus gel layer. Thiomers mimic therefore the natural mechanism of secreted mucus glycoproteins, which are also covalently anchored in the mucus layer by the formation of disulfide bonds-the bridging structure most commonly encountered in biological systems. So far the cationic thiomers chitosan-cysteine, chitosan-thiobutylamidine as well as chitosan-thioglycolic acid and the anionic thiomers poly(acylic acid)-cysteine, poly(acrylic acid)-cysteamine, carboxy-methylcellulose-cysteine and alginate-cysteine have been generated. Due to the immobilization of thiol groups on mucoadhesive basis polymers, their mucoadhesive properties are 2- up to 140-fold improved. The higher efficacy of this new generation of mucoadhesive polymers in comparison to the corresponding unmodified mucoadhesive basis polymers could be verified via various in vivo studies on various mucosal membranes in different animal species and in humans. The development of first commercial available products comprising thiomers is in progress. Within this review an overview of the mechanism of adhesion and the design of thiomers as well as delivery systems comprising thiomers and their in vivo performance is provided.

  2. Inner Ear Drug Delivery for Auditory Applications

    PubMed Central

    Swan, Erin E. Leary; Mescher, Mark J.; Sewell, William F.; Tao, Sarah L.; Borenstein, Jeffrey T.

    2008-01-01

    Many inner ear disorders cannot be adequately treated by systemic drug delivery. A blood-cochlear barrier exists, similar physiologically to the blood-brain barrier, which limits the concentration and size of molecules able to leave the circulation and gain access to the cells of the inner ear. However, research in novel therapeutics and delivery systems has led to significant progress in the development of local methods of drug delivery to the inner ear. Intratympanic approaches, which deliver therapeutics to the middle ear, rely on permeation through tissue for access to the structures of the inner ear, whereas intracochlear methods are able to directly insert drugs into the inner ear. Innovative drug delivery systems to treat various inner ear ailments such as ototoxicity, sudden sensorineural hearing loss, autoimmune inner ear disease, and for preserving neurons and regenerating sensory cells are being explored. PMID:18848590

  3. Preparation and evaluation of mucoadhesive cefdinir microcapsules.

    PubMed

    Veerareddy, Prabhakar Reddy; Tedla, Swathi; Banda, Srinivas Reddy; Bandari, Suresh; Jukanti, Raju

    2011-04-01

    The mucoadhesive microcapsules were prepared by using various concentrations of three different mucoadhesive polymers, namely, chitosan, Carbopol 934P, and methyl cellulose as wall materials and cefdinir as the core material employing orificeionic gelation method. The prepared microcapsules were characterized by scanning electron microscope (SEM) and Fourier transform infrared spectrometry (FT-IR). The prepared microcapsules were found to be spherical with particle size ranging from 765±20 to 985±10 μm and encapsulation efficiencies in the range of 55%-92%. The formulation containing Carbopol 934P as mucoadhesive polymer was found to be best with particle size 946±10 μm. The ex vivo wash-off test showed that the mucoadhesion after 1 h was 80% and the in vitro drug release was extended for more than 12 h. FT-IR spectra indicate that there was no interaction between drug and the polymers used in the formulation. Cefdinir is better absorbed from the upper part of the gastrointestinal tract, it suffers from low oral bioavailability (20-30%), shorter biological half-life (1-2 h), and less transit time. Thus, it can be concluded that microcapsules prepared using Carbopol 934P have promising properties for use as mucoadhesive carrier to increase the residence time of cefdinir.

  4. Preparation and evaluation of mucoadhesive cefdinir microcapsules

    PubMed Central

    Veerareddy, Prabhakar Reddy; Tedla, Swathi; Banda, Srinivas Reddy; Bandari, Suresh; Jukanti, Raju

    2011-01-01

    The mucoadhesive microcapsules were prepared by using various concentrations of three different mucoadhesive polymers, namely, chitosan, Carbopol 934P, and methyl cellulose as wall materials and cefdinir as the core material employing orificeionic gelation method. The prepared microcapsules were characterized by scanning electron microscope (SEM) and Fourier transform infrared spectrometry (FT-IR). The prepared microcapsules were found to be spherical with particle size ranging from 765±20 to 985±10 μm and encapsulation efficiencies in the range of 55%–92%. The formulation containing Carbopol 934P as mucoadhesive polymer was found to be best with particle size 946±10 μm. The ex vivo wash-off test showed that the mucoadhesion after 1 h was 80% and the in vitro drug release was extended for more than 12 h. FT-IR spectra indicate that there was no interaction between drug and the polymers used in the formulation. Cefdinir is better absorbed from the upper part of the gastrointestinal tract, it suffers from low oral bioavailability (20–30%), shorter biological half-life (1–2 h), and less transit time. Thus, it can be concluded that microcapsules prepared using Carbopol 934P have promising properties for use as mucoadhesive carrier to increase the residence time of cefdinir. PMID:22171303

  5. Chitosan Microspheres in Novel Drug Delivery Systems

    PubMed Central

    Mitra, Analava; Dey, Baishakhi

    2011-01-01

    The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems. PMID:22707817

  6. Transpapillary drug delivery to the breast.

    PubMed

    Dave, Kaushalkumar; Averineni, Ranjith; Sahdev, Preety; Perumal, Omathanu

    2014-01-01

    The study was aimed at investigating localized topical drug delivery to the breast via mammary papilla (nipple). 5-fluorouracil (5-FU) and estradiol (EST) were used as model hydrophilic and hydrophobic compounds respectively. Porcine and human nipple were used for in-vitro penetration studies. The removal of keratin plug enhanced the drug transport through the nipple. The drug penetration was significantly higher through the nipple compared to breast skin. The drug's lipophilicity had a significant influence on drug penetration through nipple. The ducts in the nipple served as a major transport pathway to the underlying breast tissue. Results showed that porcine nipple could be a potential model for human nipple. The topical application of 5-FU on the rat nipple resulted in high drug concentration in the breast and minimal drug levels in plasma and other organs. Overall, the findings from this study demonstrate the feasibility of localized drug delivery to the breast through nipple.

  7. Colloidal polymeric nanoparticles and brain drug delivery.

    PubMed

    Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2009-07-01

    The blood brain barrier protects the brain from harmful substances in the blood stream and has stopped the development of many powerful and interesting drugs candidates for central nervous system due to the low poor distribution and by efflux mechanisms. Many different approaches have been developed in order to overcome this barrier and the drug gain access to the brain. The polymeric nanoparticles are efficient colloidal systems that have been investigated to the brain drug delivery. This review will focus on the current strategies for brain drug delivery emphasizing the properties and characteristics of polymeric nanoparticles for this purpose.

  8. Vesicular carriers for dermal drug delivery.

    PubMed

    Sinico, Chiara; Fadda, Anna Maria

    2009-08-01

    The skin can offer several advantages as a route of drug administration although its barrier nature makes it difficult for most drugs to penetrate into and permeate through it. During the past decades there has been a lot of interest in lipid vesicles as a tool to improve drug topical delivery. Vesicular systems such as liposomes, niosomes, ethosomes and elastic, deformable vesicles provide an alternative for improved skin drug delivery. The function of vesicles as topical delivery systems is controversial with variable effects being reported in relation to the type of vesicles and their composition. In fact, vesicles can act as drug carriers controlling active release; they can provide a localized depot in the skin for dermally active compounds and enhance transdermal drug delivery. A wide variety of lipids and surfactants can be used to prepare vesicles, which are commonly composed of phospholipids (liposomes) or non-ionic surfactants (niosomes). Vesicle composition and preparation method influence their physicochemical properties (size, charge, lamellarity, thermodynamic state, deformability) and therefore their efficacy as drug delivery systems. A review of vesicle value in localizing drugs within the skin at the site of action will be provided with emphasis on their potential mechanism of action.

  9. Formulation Design, Optimization and Pharmacodynamic Evaluation of Sustained Release Mucoadhesive Microcapsules of Venlafaxine HCl

    PubMed Central

    Swain, S.; Behera, A.; Dinda, S. C.; Patra, C. N.; Jammula, Sruti; Beg, S.; Rao, M. E. B.

    2014-01-01

    The objective of present research work was to design and characterize the venlafaxine HCl-loaded sodium alginate-based mucoadhesive microcapsules by ionic gelation technique using HPMC K100M as mucoadhesive polymer. The Placket-Burman Design was applied for preliminary screening of the formulations and systematic optimization by using Box-Behnken Design. The prepared microcapsules were characterized for drug content, entrapment efficiency, micromeritic properties, particle size, swelling index, mucoadhesive strength, in vitro drug release and in vivo antidepressant activity. FTIR and differential scanning calorimetry studies showed no incompatibility. Surface morphology studies revealed spherical nature of the prepared microcapsules. In vitro drug release studies revealed sustained release by diffusion mechanism. Further, the microcapsules were effective in reducing the depression induced by forced swimming test in Sprague-Dawley rats compared to the pure drug. The microcapsules were found to be stable under accelerated stability conditions, which suggest them as better alternative delivery systems for enhanced therapeutic efficacy of antidepressant drug, venlafaxine HCl. PMID:25284934

  10. Nuclear drug delivery for cancer chemotherapy.

    PubMed

    Sui, Meihua; Liu, Wenwen; Shen, Youqing

    2011-10-30

    Nanosystems with unique physical and biological properties have been extensively explored for cancer targeted intracellular delivery of small-molecular chemotherapeutic drugs to increase their therapeutic efficacies and to minimize their side effects. A large number of anticancer drugs are DNA-toxins that bind nuclear DNA or its associated enzymes to exert their cytotoxicity to cancer cells. After entering tumor cells, they need to be further delivered to the nucleus for actions. Herein, we discuss the biological barriers and summarize recent progress of nuclear drug delivery for cancer chemotherapy, emphasizing strategies that appear useful for design of vehicles capable of delivering drugs to the nucleus, particularly for in vivo applications. The existing obstacles or problems that need to be overcome before successful applications of nuclear drug delivery for cancer chemotherapy are also discussed.

  11. Molecular imprinted polymers as drug delivery vehicles.

    PubMed

    Zaidi, Shabi Abbas

    2016-09-01

    This review is aimed to discuss the molecular imprinted polymer (MIP)-based drug delivery systems (DDS). Molecular imprinted polymers have proved to possess the potential and also as a suitable material in several areas over a long period of time. However, only recently it has been employed for pharmaceuticals and biomedical applications, particularly as drug delivery vehicles due to properties including selective recognition generated from imprinting the desired analyte, favorable in harsh experimental conditions, and feedback-controlled recognitive drug release. Hence, this review will discuss their synthesis, the reason they are selected as drug delivery vehicles and for their applications in several drug administration routes (i.e. transdermal, ocular and gastrointestinal or stimuli-reactive routes).

  12. Calcium phosphate ceramics in drug delivery

    NASA Astrophysics Data System (ADS)

    Bose, Susmita; Tarafder, Solaiman; Edgington, Joe; Bandyopadhyay, Amit

    2011-04-01

    Calcium phosphate (CaP) particulates, cements and scaffolds have attracted significant interest as drug delivery vehicles. CaP systems, including both hydroxyapaptite and tricalcium phosphates, possess variable stoichiometry, functionality and dissolution properties which make them suitable for cellular delivery. Their chemical similarity to bone and thus biocompatibility, as well as variable surface charge density contribute to their controlled release properties. Among specific research areas, nanoparticle size, morphology, surface area due to porosity, and chemistry controlled release kinetics are the most active. This article discusses CaP systems in their particulate, cements, and scaffold forms for drug, protein, and growth factor delivery toward orthopedic and dental applications.

  13. Microneedles for drug and vaccine delivery

    PubMed Central

    Kim, Yeu-Chun; Park, Jung-Hwan; Prausnitz, Mark R.

    2012-01-01

    Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990’s when microfabrication technology enabled their manufacture as (i) solid microneedles for skin pretreatment to increase skin permeability, (ii) microneedles coated with drug that dissolves off in the skin, (iii) polymer microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications. PMID:22575858

  14. Designing hydrogels for controlled drug delivery

    NASA Astrophysics Data System (ADS)

    Li, Jianyu; Mooney, David J.

    2016-12-01

    Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform on which various physiochemical interactions with the encapsulated drugs occur to control drug release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel-drug interactions across the network, mesh and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.

  15. Polymethacrylate microparticles gel for topical drug delivery.

    PubMed

    Labouta, Hagar Ibrahim; El-Khordagui, Labiba K

    2010-10-01

    Evaluating the potentials of particulate delivery systems in topical drug delivery. Polymethacrylate microparticles (MPs) incorporating verapamil hydrochloride (VRP) as a model hydrophilic drug with potential topical clinical uses, using Eudragit RS100 and Eudragit L100 were prepared for the formulation of a composite topical gel. The effect of initial drug loading, polymer composition, particularly the proportion of Eudragit L100 as an interacting polymer component and the HLB of the dispersing agent on MPs characteristics was investigated. A test MPs formulation was incorporated in gel and evaluated for drug release and human skin permeation. MPs showed high % incorporation efficiency and % yield. Composition of the hybrid polymer matrix was a main determinant of MPs characteristics, particularly drug release. Factors known to influence drug release such as MPs size and high drug solubility were outweighed by strong VRP-Eudragit L100 interaction. The developed MPs gel showed controlled VRP release and reduced skin retention compared to a free drug gel. Topical drug delivery and skin retention could be modulated using particulate delivery systems. From a practical standpoint, the VRP gel developed may offer advantage in a range of dermatological conditions, in response to the growing off-label topical use of VRP.

  16. Progress in antiretroviral drug delivery using nanotechnology

    PubMed Central

    Mallipeddi, Rama; Rohan, Lisa Cencia

    2010-01-01

    There are currently a number of antiretroviral drugs that have been approved by the Food and Drug Administration for use in the treatment of human immunodeficiency virus (HIV). More recently, antiretrovirals are being evaluated in the clinic for prevention of HIV infection. Due to the challenging nature of treatment and prevention of this disease, the use of nanocarriers to achieve more efficient delivery of antiretroviral drugs has been studied. Various forms of nanocarriers, such as nanoparticles (polymeric, inorganic, and solid lipid), liposomes, polymeric micelles, dendrimers, cyclodextrins, and cell-based nanoformulations have been studied for delivery of drugs intended for HIV prevention or therapy. The aim of this review is to provide a summary of the application of nanocarrier systems to the delivery of anti-HIV drugs, specifically antiretrovirals. For anti-HIV drugs to be effective, adequate distribution to specific sites in the body must be achieved, and effective drug concentrations must be maintained at those sites for the required period of time. Nanocarriers provide a means to overcome cellular and anatomical barriers to drug delivery. Their application in the area of HIV prevention and therapy may lead to the development of more effective drug products for combating this pandemic disease. PMID:20957115

  17. Hydrogen peroxide mediated transvaginal drug delivery.

    PubMed

    Fatakdawala, Hussain; Uhland, Scott A

    2011-05-16

    Simple, safe and effective permeability enhancers are crucial for successful non-invasive drug delivery methods. We seek local permeability augmentation mechanisms for integration into passive or active architectures in order to enable novel therapeutic delivery routes of the target drug while minimizing drug formulation challenges. This study explores the efficacy of hydrogen peroxide (HP) as a permeability enhancer for transmucosal delivery of macromolecules. HP at low concentrations (2–8 mM) is an effective permeability enhancer that is locally metabolized and safe. HP improves drug permeation through mucosa by altering tight junctions (TJ) between cells and oxidizing enzymes that function to degrade the foreign species. Results from trans-epithelial electrical resistance measurements and cell viability assay show reversible disassembly of TJ with minimal cell damage demonstrating the feasibility of HP as a safe permeability enhancer for drug delivery. Permeation studies show that HP treatment of cell cultured vaginal mucosa significantly enhances the permeability to insulin by more than an order of magnitude. This work lays foundation for the development of a drug delivery platform that administers drug doses by enhancing the permeability of local epithelial tissue via a separate HP treatment step.

  18. Transpapillary Drug Delivery to the Breast

    PubMed Central

    Dave, Kaushalkumar; Averineni, Ranjith; Sahdev, Preety; Perumal, Omathanu

    2014-01-01

    The study was aimed at investigating localized topical drug delivery to the breast via mammary papilla (nipple). 5-fluorouracil (5-FU) and estradiol (EST) were used as model hydrophilic and hydrophobic compounds respectively. Porcine and human nipple were used for in-vitro penetration studies. The removal of keratin plug enhanced the drug transport through the nipple. The drug penetration was significantly higher through the nipple compared to breast skin. The drug’s lipophilicity had a significant influence on drug penetration through nipple. The ducts in the nipple served as a major transport pathway to the underlying breast tissue. Results showed that porcine nipple could be a potential model for human nipple. The topical application of 5-FU on the rat nipple resulted in high drug concentration in the breast and minimal drug levels in plasma and other organs. Overall, the findings from this study demonstrate the feasibility of localized drug delivery to the breast through nipple. PMID:25545150

  19. Microfluidic device for drug delivery

    NASA Technical Reports Server (NTRS)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2010-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  20. Novel biodegradable nanocarriers for enhanced drug delivery.

    PubMed

    Gagliardi, Mariacristina

    2016-12-01

    With the refinement of functional properties, the interest around biodegradable materials, in biorelated applications and, in particular, in their use as controlled drug-delivery systems, increased in the last decades. Biodegradable materials are an ideal platform to obtain nanoparticles for spatiotemporal controlled drug delivery for the in vivo administration, thanks to their biocompatibility, functionalizability, the control exerted on delivery rates and the complete degradation. Their application in systems for cancer treatment, brain and cardiovascular diseases is already a consolidated practice in research, while the bench-to-bedside translation is still late. This review aims at summarizing reported applications of biodegradable materials to obtain drug-delivery nanoparticles in the last few years, giving a complete overview of pros and cons related to degradable nanomedicaments.

  1. Intelligent, self-powered, drug delivery systems.

    PubMed

    Patra, Debabrata; Sengupta, Samudra; Duan, Wentao; Zhang, Hua; Pavlick, Ryan; Sen, Ayusman

    2013-02-21

    Self-propelled nano/micromotors and pumps are considered to be next generation drug delivery systems since the carriers can either propel themselves ("motor"-based drug delivery) or be delivered ("pump"-based drug delivery) to the target in response to specific biomarkers. Recently, there has been significant advancement towards developing nano/microtransporters into proof-of-concept tools for biomedical applications. This review encompasses the progress made to date on the design of synthetic nano/micromotors and pumps with respect to transportation and delivery of cargo at specific locations. Looking ahead, it is possible to imagine a day when intelligent machines navigate through the human body and perform challenging tasks.

  2. Novel drug delivery systems for glaucoma

    PubMed Central

    Lavik, E; Kuehn, M H; Kwon, Y H

    2011-01-01

    Reduction of intraocular pressure (IOP) by pharmaceutical or surgical means has long been the standard treatment for glaucoma. A number of excellent drugs are available that are effective in reducing IOP. These drugs are typically applied as eye drops. However, patient adherence can be poor, thus reducing the clinical efficacy of the drugs. Several novel delivery systems designed to address the issue of adherence and to ensure consistent reduction of IOP are currently under development. These delivery systems include contact lenses-releasing glaucoma medications, injectables such as biodegradable micro- and nanoparticles, and surgically implanted systems. These new technologies are aimed at increasing clinical efficacy by offering multiple delivery options and are capable of managing IOP for several months. There is also a desire to have complementary neuroprotective approaches for those who continue to show progression, despite IOP reduction. Many potential neuroprotective agents are not suitable for traditional oral or drop formulations. Their potential is dependent on developing suitable delivery systems that can provide the drugs in a sustained, local manner to the retina and optic nerve. Drug delivery systems have the potential to improve patient adherence, reduce side effects, increase efficacy, and ultimately, preserve sight for glaucoma patients. In this review, we discuss benefits and limitations of the current systems of delivery and application, as well as those on the horizon. PMID:21475311

  3. Fungal diseases: could nanostructured drug delivery systems be a novel paradigm for therapy?

    PubMed Central

    Voltan, Aline Raquel; Quindós, Guillermo; Alarcón, Kaila P Medina; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José Soares; Chorilli, Marlus

    2016-01-01

    Invasive mycoses are a major problem for immunocompromised individuals and patients in intensive care units. Morbidity and mortality rates of these infections are high because of late diagnosis and delayed treatment. Moreover, the number of available antifungal agents is low, and there are problems with toxicity and resistance. Alternatives for treating invasive fungal infections are necessary. Nanostructured systems could be excellent carriers for antifungal drugs, reducing toxicity and targeting their action. The use of nanostructured systems for antifungal therapy began in the 1990s, with the appearance of lipid formulations of amphotericin B. This review encompasses different antifungal drug delivery systems, such as liposomes, carriers based on solid lipids and nanostructure lipids, polymeric nanoparticles, dendrimers, and others. All these delivery systems have advantages and disadvantages. Main advantages are the improvement in the antifungal properties, such as bioavailability, reduction in toxicity, and target tissue, which facilitates innovative therapeutic techniques. Conversely, a major disadvantage is the high cost of production. In the near future, the use of nanosystems for drug delivery strategies can be used for delivering peptides, including mucoadhesive systems for the treatment of oral and vaginal candidiasis. PMID:27540288

  4. Fungal diseases: could nanostructured drug delivery systems be a novel paradigm for therapy?

    PubMed

    Voltan, Aline Raquel; Quindós, Guillermo; Alarcón, Kaila P Medina; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José Soares; Chorilli, Marlus

    2016-01-01

    Invasive mycoses are a major problem for immunocompromised individuals and patients in intensive care units. Morbidity and mortality rates of these infections are high because of late diagnosis and delayed treatment. Moreover, the number of available antifungal agents is low, and there are problems with toxicity and resistance. Alternatives for treating invasive fungal infections are necessary. Nanostructured systems could be excellent carriers for antifungal drugs, reducing toxicity and targeting their action. The use of nanostructured systems for antifungal therapy began in the 1990s, with the appearance of lipid formulations of amphotericin B. This review encompasses different antifungal drug delivery systems, such as liposomes, carriers based on solid lipids and nanostructure lipids, polymeric nanoparticles, dendrimers, and others. All these delivery systems have advantages and disadvantages. Main advantages are the improvement in the antifungal properties, such as bioavailability, reduction in toxicity, and target tissue, which facilitates innovative therapeutic techniques. Conversely, a major disadvantage is the high cost of production. In the near future, the use of nanosystems for drug delivery strategies can be used for delivering peptides, including mucoadhesive systems for the treatment of oral and vaginal candidiasis.

  5. Topical drug delivery to the eye: dorzolamide.

    PubMed

    Loftsson, Thorsteinn; Jansook, Phatsawee; Stefánsson, Einar

    2012-11-01

    Topically applied carbonic anhydrase inhibitors (CAIs) in eye drop solutions are commonly used to treat glaucoma. However, local eye irritation and multiple daily administrations may hamper their clinical usefulness. Aqueous eye drop formulations that improve their topical bioavailability and reduce their eye irritation can improve their clinical efficacy. Earlier studies showed that dorzolamide and closely related CAIs are more effectively delivered into the eye from acidic eye drop solutions than from comparable neutral solutions. Consequently, dorzolamide was marketed as an aqueous pH 5.6 eye drop solution (Trusopt(®) , Merck). Later, it was shown that increasing the pH of the eye drops from pH 5.6 to physiologic pH significantly reduced their local irritation. Earlier attempts to use cyclodextrins (CDs) as ocular penetration enhancers in dorzolamide eye drop solutions failed since; although the CDs were able to enhance the aqueous solubility of dorzolamide, increasing the pH from 5.6 to physiologic pH reduced the ability of the drug to permeate into the eye. Later, it was discovered that formulating the drug as aqueous dorzolamide/γCD eye drop microparticle suspension resulted in significant bioavailability enhancement. The solid dorzolamide/γCD microparticles are mucoadhesive and release dorzolamide into the aqueous tear fluid for extended time period. Consequently, sustained high dorzolamide concentrations in aqueous humour and various eye tissues were observed after single administration of the aqueous dorzolamide/γCD eye drop microsuspension. The microsuspension has a potential of being developed into a once-a-day eye drop product. This article reviews the physicochemical properties of dorzolamide, its permeation characteristics and topical bioavailability. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

  6. Brain Mitochondrial Drug Delivery: Influence of Drug Physicochemical Properties

    PubMed Central

    Durazo, Shelley A.; Kadam, Rajendra S.; Drechsel, Derek; Patel, Manisha

    2017-01-01

    Purpose To determine the influence of drug physicochemical properties on brain mitochondrial delivery of 20 drugs at physiological pH. Methods The delivery of 8 cationic drugs (beta-blockers), 6 neutral drugs (corticosteroids), and 6 anionic drugs (non-steroidal anti-inflammatory drugs, NSAIDs) to isolated rat brain mitochondria was determined with and without membrane depolarization. Multiple linear regression was used to determine whether lipophilicity (Log D), charge, polarizability, polar surface area (PSA), and molecular weight influence mitochondrial delivery. Results The Log D for beta-blockers, corticosteroids, and NSAIDs was in the range of −1.41 to 1.37, 0.72 to 2.97, and −0.98 to 2, respectively. The % mitochondrial uptake increased exponentially with an increase in Log D for each class of drugs, with the uptake at a given lipophilicity obeying the rank order cationic>anionic>neutral. Valinomycin reduced membrane potential and the delivery of positively charged propranolol and betaxolol. The best equation for the combined data set was Log % Uptake=0.333 Log D+ 0.157 Charge – 0.887 Log PSA+2.032 (R2=0.738). Conclusions Drug lipopohilicity, charge, and polar surface area and membrane potential influence mitochondrial drug delivery, with the uptake of positively charged, lipophilic molecules being the most efficient. PMID:21796482

  7. Brain mitochondrial drug delivery: influence of drug physicochemical properties.

    PubMed

    Durazo, Shelley A; Kadam, Rajendra S; Drechsel, Derek; Patel, Manisha; Kompella, Uday B

    2011-11-01

    To determine the influence of drug physicochemical properties on brain mitochondrial delivery of 20 drugs at physiological pH. The delivery of 8 cationic drugs (beta-blockers), 6 neutral drugs (corticosteroids), and 6 anionic drugs (non-steroidal anti-inflammatory drugs, NSAIDs) to isolated rat brain mitochondria was determined with and without membrane depolarization. Multiple linear regression was used to determine whether lipophilicity (Log D), charge, polarizability, polar surface area (PSA), and molecular weight influence mitochondrial delivery. The Log D for beta-blockers, corticosteroids, and NSAIDs was in the range of -1.41 to 1.37, 0.72 to 2.97, and -0.98 to 2, respectively. The % mitochondrial uptake increased exponentially with an increase in Log D for each class of drugs, with the uptake at a given lipophilicity obeying the rank order cationic>anionic>neutral. Valinomycin reduced membrane potential and the delivery of positively charged propranolol and betaxolol. The best equation for the combined data set was Log % Uptake = 0.333 Log D + 0.157 Charge - 0.887 Log PSA + 2.032 (R(2) = 0.738). Drug lipopohilicity, charge, and polar surface area and membrane potential influence mitochondrial drug delivery, with the uptake of positively charged, lipophilic molecules being the most efficient.

  8. Mucoadhesive dosage form of lidocaine hydrochloride: I. Mucoadhesive and physicochemical characterization.

    PubMed

    Abu-Huwaij, Rana; Assaf, Shereen; Salem, Mutaz; Sallam, Alsayed

    2007-08-01

    The aim of this study was to characterize a buccal mucoadhesive film using lidocaine and its hydrochloride salt (LDHCL) as a model drug. Buccal films were developed using carbopol 971P as a mucoadhesive polymer, and glycerol as a plasticizer. Scanning Electron Microscope, Differential Scanning Calorimetry, X-ray powder diffraction, and Fourier Transform Infra Red techniques were used to characterize the mucoadhesive films. Bioadhesive properties were evaluated using the Universal Instron Instrument with chicken pouch as a model tissue. LDHCL and its base were present in carbopol 971P films in a molecular dispersion state without exerting any effect on the glass transition of these films. The mucoadhesive force between the chicken pouches and the film containing glycerol did not change by time during the tested period (1-20 min), while increased with increasing the amount of glycerol (10-40% w/w of polymer content). Furthermore, a linear increase in the mucoadhesive force was accompanied by the increase in the film thickness, while a linear decrease followed by plateau was obtained when loading the patch with LDHCL at concentration above 1 mg/cm(2). Loading carbopol film with lidocaine base, in a concentration up to 6 mg/cm(2) decreased linearly the mucoadhesive properties, which could be attributed to salt formation between the acidic carboxylic moiety of carbopol and basic lidocaine.

  9. Lipid-Based Drug Delivery Systems

    PubMed Central

    Shrestha, Hina; Bala, Rajni; Arora, Sandeep

    2014-01-01

    The principle objective of formulation of lipid-based drugs is to enhance their bioavailability. The use of lipids in drug delivery is no more a new trend now but is still the promising concept. Lipid-based drug delivery systems (LBDDS) are one of the emerging technologies designed to address challenges like the solubility and bioavailability of poorly water-soluble drugs. Lipid-based formulations can be tailored to meet a wide range of product requirements dictated by disease indication, route of administration, cost consideration, product stability, toxicity, and efficacy. These formulations are also a commercially viable strategy to formulate pharmaceuticals, for topical, oral, pulmonary, or parenteral delivery. In addition, lipid-based formulations have been shown to reduce the toxicity of various drugs by changing the biodistribution of the drug away from sensitive organs. However, the number of applications for lipid-based formulations has expanded as the nature and type of active drugs under investigation have become more varied. This paper mainly focuses on novel lipid-based formulations, namely, emulsions, vesicular systems, and lipid particulate systems and their subcategories as well as on their prominent applications in pharmaceutical drug delivery. PMID:26556202

  10. Electroresponsive nanoparticles for drug delivery on demand

    NASA Astrophysics Data System (ADS)

    Samanta, Devleena; Hosseini-Nassab, Niloufar; Zare, Richard N.

    2016-04-01

    The potential of electroresponsive conducting polymer nanoparticles to be used as general drug delivery systems that allow electrically pulsed, linearly scalable, and on demand release of incorporated drugs is demonstrated. As examples, facile release from polypyrrole nanoparticles is shown for fluorescein, a highly water-soluble model compound, piroxicam, a lipophilic small molecule drug, and insulin, a large hydrophilic peptide hormone. The drug loading is about 13 wt% and release is accomplished in a few seconds by applying a weak constant current or voltage. To identify the parameters that should be finely tuned to tailor the carrier system for the release of the therapeutic molecule of interest, a systematic study of the factors that affect drug delivery is performed, using fluorescein as a model compound. The parameters studied include current, time, voltage, pH, temperature, particle concentration, and ionic strength. Results indicate that there are several degrees of freedom that can be optimized for efficient drug delivery. The ability to modulate linearly drug release from conducting polymers with the applied stimulus can be utilized to design programmable and minimally invasive drug delivery devices.

  11. Cellulose based polymeric systems in drug delivery

    USDA-ARS?s Scientific Manuscript database

    The pharmaceutical industry requires the development of biodegradable, biocompatible, non toxic, site specific drug delivery polymers, which can be easily coupled with drugs to be delivered orally, topically, locally, or parenterally. The use of the most abundant biopolymer, cellulose along with its...

  12. Spray Drying Tenofovir Loaded Mucoadhesive and pH-Sensitive Microspheres Intended for HIV Prevention

    PubMed Central

    Zhang, Tao; Zhang, Chi; Agrahari, Vivek; Murowchick, James B.; Oyler, Nathan A.; Youan, Bi-Botti C.

    2013-01-01

    Purpose To develop spray dried mucoadhesive and pH-sensitive microspheres (MS) based on polymethacrylate salt intended for vaginal delivery of tenofovir (a model HIV microbicide) and assess their critical biological responses. Methods The formulation variables and process parameters are screened and optimized using a 24-1 fractional factorial design. The MS are characterized for size, zeta potential, yield, encapsulation efficiency, Carr’s index, drug loading, in vitro release, cytotoxicity, inflammatory responses and mucoadhesion. Results The optimal MS formulation has an average size of 4.73 µm, Zeta potential of −26.3 mV, 68.9% yield, encapsulation efficiency of 88.7%, Carr’s index of 28.3 and drug loading of 2% (w/w). The MS formulation can release 90% of its payload in the presence of simulated human semen. At a concentration of 1 mg/ml, the MS are noncytotoxic to vaginal endocervical/epithelial cells and Lactobacillus crispatus when compared to control media. There is also no statistically significant level of inflammatory cytokine (IL1-α, IL-1β, IL-6, IL-8, and IP-10) release triggered by MS. The mucoadhesive property of MS formulation is 2-fold higher than that of 1% HEC gel formulation. Conclusion These data suggest the promise of using such MS as an alternative controlled microbicide delivery template by intravaginal route for HIV prevention. PMID:23274788

  13. The wettability and swelling of selected mucoadhesive polymers in simulated saliva and vaginal fluids.

    PubMed

    Rojewska, M; Olejniczak-Rabinek, M; Bartkowiak, A; Snela, A; Prochaska, K; Lulek, J

    2017-08-01

    The surface properties play a particularly important role in the mucoadhesive drug delivery systems. In these formulations, the adsorption of polymer matrix to mucous membrane is limited by the wetting and swelling process of the polymer structure. Hence, the performance of mucoadhesive drug delivery systems made of polymeric materials depends on multiple factors, such as contact angle, surface free energy and water absorption rate. The aim of our study was to analyze the effect of model saliva and vaginal fluids on the wetting properties of selected mucoadhesive (Carbopol 974P NF, Noveon AA-1, HEC) and film-forming (Kollidon VA 64) polymers as well as their blends at the weight ratio 1:1 and 1:1:1, prepared in the form of discs. Surface properties of the discs were determined by measurements of advancing contact angle on the surface of polymers and their blends using the sessile drop method. The surface energy was determined by the OWRK method. Additionally, the mass swelling factor and hydration percentage of examined polymers and their blends in simulated biological fluids were evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Hp-β-CD-Voriconazole In Situ Gelling System for Ocular Drug Delivery: In Vitro, Stability, and Antifungal Activities Assessment

    PubMed Central

    Pawar, Pravin; Kashyap, Heena; Malhotra, Sakshi; Sindhu, Rakesh

    2013-01-01

    The objective of the present study was to design ophthalmic delivery systems based on polymeric carriers that undergo sol-to-gel transition upon change in temperature or in the presence of cations so as to prolong the effect of HP-β-CD Voriconazole (VCZ) in situ gelling formulations. The in situ gelling formulations of Voriconazole were prepared by using pluronic F-127 (PF-127) or with combination of pluronic F-68 (PF-68) and sodium alginate by cold method technique. The prepared formulations were evaluated for their physical appearance, drug content, gelation temperature (Tgel), in vitro permeation studies, rheological properties, mucoadhesion studies, antifungal studies, and stability studies. All batches of in situ formulations had satisfactory pH ranging from 6.8 to 7.4, drug content between 95% and 100%, showing uniform distribution of drug. As the concentration of each polymeric component was increased, that is, PF-68 and sodium alginate, there was a decrease in Tgel with increase in viscosity and mucoadhesive strength. The in vitro drug release decreased with increase in polymeric concentrations. The stability data concluded that all formulations showed the low degradation and maximum shelf life of 2 years. The antifungal efficiency of the selected formulation against Candida albicans and Asperigillus fumigatus confirmed that designed formulation has prolonged effect and retained its properties against fungal infection. PMID:23762839

  15. Microfabrication Technologies for Oral Drug Delivery

    PubMed Central

    Sant, Shilpa; Tao, Sarah L.; Fisher, Omar; Xu, Qiaobing; Peppas, Nicholas A.; Khademhosseini, Ali

    2012-01-01

    Micro-/nanoscale technologies such as lithographic techniques and microfluidics offer promising avenues to revolutionalize the fields of tissue engineering, drug discovery, diagnostics and personalized medicine. Microfabrication techniques are being explored for drug delivery applications due to their ability to combine several features such as precise shape and size into a single drug delivery vehicle. They also offer to create unique asymmetrical features incorporated into single or multiple reservoir systems maximizing contact area with the intestinal lining. Combined with intelligent materials, such microfabricated platforms can be designed to be bioadhesive and stimuli-responsive. Apart from drug delivery devices, microfabrication technologies offer exciting opportunities to create biomimetic gastrointestinal tract models incorporating physiological cell types, flow patterns and brush-border like structures. Here we review the recent developments in this field with a focus on the applications of microfabrication in the development of oral drug delivery devices and biomimetic gastrointestinal tract models that can be used to evaluate the drug delivery efficacy. PMID:22166590

  16. A pulsed mode electrolytic drug delivery device

    NASA Astrophysics Data System (ADS)

    Yi, Ying; Buttner, Ulrich; Carreno, Armando A. A.; Conchouso, David; Foulds, Ian G.

    2015-10-01

    This paper reports the design of a proof-of-concept drug delivery device that is actuated using the bubbles formed during electrolysis. The device uses a platinum (Pt) coated nickel (Ni) metal foam and a solid drug in reservoir (SDR) approach to improve the device’s performance. This electrochemically-driven pump has many features that are unlike conventional drug delivery devices: it is capable of pumping periodically and being refilled automatically; it features drug release control; and it enables targeted delivery. Pt-coated metal foam is used as a catalytic reforming element, which reduces the period of each delivery cycle. Two methods were used for fabricating the Pt-coated metal: sputtering and electroplating. Of these two methods, the sputtered Pt-coated metal foam has a higher pumping rate; it also has a comparable recombination rate when compared to the electroplated Pt-coated metal foam. The only drawback of this catalytic reformer is that it consumes nickel scaffold. Considering long-term applications, the electroplated Pt metal foam was selected for drug delivery, where a controlled drug release rate of 2.2 μg  ±  0.3 μg per actuation pulse was achieved using 4 mW of power.

  17. Nanotech approaches to drug delivery and imaging.

    PubMed

    Sahoo, Sanjeeb K; Labhasetwar, Vinod

    2003-12-15

    Nanotechnology, a multidisciplinary scientific undertaking, involves creation and utilization of materials, devices or systems on the nanometer scale. The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to create innovations and play a critical role in various biomedical applications, not only in drug delivery, but also in molecular imaging, biomarkers and biosensors. Target-specific drug therapy and methods for early diagnosis of pathologies are the priority research areas where nanotechnology would play a vital role. This review considers different nanotechnology-based drug delivery and imaging approaches, and their economic impact on pharmaceutical and biomedical industries.

  18. Liposome-like Nanostructures for Drug Delivery

    PubMed Central

    Gao, Weiwei; Hu, Che-Ming J.; Fang, Ronnie H.; Zhang, Liangfang

    2013-01-01

    Liposomes are a class of well-established drug carriers that have found numerous therapeutic applications. The success of liposomes, together with recent advancements in nanotechnology, has motivated the development of various novel liposome-like nanostructures with improved drug delivery performance. These nanostructures can be categorized into five major varieties, namely: (1) polymer-stabilized liposomes, (2) nanoparticle-stabilized liposomes, (3) core-shell lipid-polymer hybrid nanoparticles, (4) natural membrane-derived vesicles, and (5) natural membrane coated nanoparticles. They have received significant attention and have become popular drug delivery platforms. Herein, we discuss the unique strengths of these liposome-like platforms in drug delivery, with a particular emphasis on how liposome-inspired novel designs have led to improved therapeutic efficacy, and review recent progress made by each platform in advancing healthcare. PMID:24392221

  19. Brain drug delivery systems for neurodegenerative disorders.

    PubMed

    Garbayo, E; Ansorena, E; Blanco-Prieto, M J

    2012-09-01

    Neurodegenerative disorders (NDs) are rapidly increasing as population ages. However, successful treatments for NDs have so far been limited and drug delivery to the brain remains one of the major challenges to overcome. There has recently been growing interest in the development of drug delivery systems (DDS) for local or systemic brain administration. DDS are able to improve the pharmacological and therapeutic properties of conventional drugs and reduce their side effects. The present review provides a concise overview of the recent advances made in the field of brain drug delivery for treating neurodegenerative disorders. Examples include polymeric micro and nanoparticles, lipidic nanoparticles, pegylated liposomes, microemulsions and nanogels that have been tested in experimental models of Parkinson's, Alzheimer's and Huntington's disease. Overall, the results reviewed here show that DDS have great potential for NDs treatment.

  20. Drug delivery approaches for breast cancer.

    PubMed

    Singh, Santosh Kumar; Singh, Shriti; Lillard, James W; Singh, Rajesh

    2017-01-01

    Breast cancer is one of the most common cancers affecting women worldwide. The controlled release of drugs to the precise site of the disease using a nanocarrier vehicle increases the therapeutic efficiency of the drugs. Nanotechnology-based approaches used to endorse clinical improvement from a disease also help to understand the interaction of malignant cells with their microenvironment. Receptor-based targeting is another approach for drug delivery which is undergoing clinical trials. Nanoparticles (NPs) delivery has been proven to promise high loading capacity, less toxicity, and stability of the drugs or biomolecules compared to traditional chemotherapeutic drugs. The goal of this review is to present the current problems of breast cancer therapy and discuss the NP-based targeting to overcome the hurdles of conventional drug therapy approach.

  1. Emulsion forming drug delivery system for lipophilic drugs.

    PubMed

    Wadhwa, Jyoti; Nair, Anroop; Kumria, Rachna

    2012-01-01

    In the recent years, there is a growing interest in the lipid-based formulations for delivery of lipophilic drugs. Due to their potential as therapeutic agents, preferably these lipid soluble drugs are incorporated into inert lipid carriers such as oils, surfactant dispersions, emulsions, liposomes etc. Among them, emulsion forming drug delivery systems appear to be a unique and industrially feasible approach to overcome the problem of low oral bioavailability associated with the BCS class II drugs. Self-emulsifying formulations are ideally isotropic mixtures of oils, surfactants and co-solvents that emulsify to form fine oil in water emulsions when introduced in aqueous media. Fine oil droplets would pass rapidly from stomach and promote wide distribution of drug throughout the GI tract, thereby overcome the slow dissolution step typically observed with solid dosage forms. Recent advances in drug carrier technologies have promulgated the development of novel drug carriers such as control release self-emulsifying pellets, microspheres, tablets, capsules etc. that have boosted the use of "self-emulsification" in drug delivery. This article reviews the different types of formulations and excipients used in emulsion forming drug delivery system to enhance the bioavailability of lipophilic drugs.

  2. Drug Delivery Research: The Invention Cycle.

    PubMed

    Park, Kinam

    2016-07-05

    Controlled drug delivery systems have been successful in introducing improved formulations for better use of existing drugs and novel delivery of biologicals. The initial success of producing many oral products and some injectable depot formulations, however, reached a plateau, and the progress over the past three decades has been slow. This is likely due to the difficulties of formulating hydrophilic, high molecular weight drugs, such as proteins and nucleic acids, for targeting specific cells, month-long sustained delivery, and pulsatile release. Since the approaches that have served well for delivery of small molecules are not applicable to large molecules, it is time to develop new methods for biologicals. The process of developing future drug delivery systems, termed as the invention cycle, is proposed, and it starts with clearly defining the problems for developing certain formulations. Once the problems are well-defined, creative imagination examines all potential options and selects the best answer and alternatives. Then, innovation takes over to generate unique solutions for developing new formulations that resolve the previously identified problems. Ultimately, the new delivery systems will have to go through a translational process to produce the final formulations for clinical use. The invention cycle also emphasizes examining the reasons for success of certain formulations, not just the reasons for failure of many systems. Implementation of the new invention cycle requires new mechanisms of funding the younger generation of scientists and a new way of identifying their achievements, thereby releasing them from the burden of short-termism.

  3. Ultrasonic Drug Delivery – A General Review

    PubMed Central

    Pitt, William G.; Husseini, Ghaleb A.; Staples, Bryant J.

    2006-01-01

    Ultrasound (US) has an ever-increasing role in the delivery of therapeutic agents including genetic material, proteins, and chemotherapeutic agents. Cavitating gas bodies such as microbubbles are the mediators through which the energy of relatively non-interactive pressure waves is concentrated to produce forces that permeabilize cell membranes and disrupt the vesicles that carry drugs. Thus the presence of microbubbles enormously enhances delivery of genetic material, proteins and smaller chemical agents. Delivery of genetic material is greatly enhanced by ultrasound in the presence of microbubbles. Attaching the DNA directly to the microbubbles or to gas-containing liposomes enhances gene uptake even further. US-enhanced gene delivery has been studied in various tissues including cardiac, vascular, skeletal muscle, tumor and even fetal tissue. US-enhanced delivery of proteins has found most application in transdermal delivery of insulin. Cavitation events reversibly disrupt the structure of the stratus corneum to allow transport of these large molecules. Other hormones and small proteins could also be delivered transdermally. Small chemotherapeutic molecules are delivered in research settings from micelles and liposomes exposed to ultrasound. Cavitation appears to play two roles: it disrupts the structure of the carrier vesicle and releases the drug; it also makes the cell membranes and capillaries more permeable to drugs. There remains a need to better understand the physics of cavitation of microbubbles and the impact that such cavitation has upon cells and drug-carrying vesicles. PMID:16296719

  4. Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs.

    PubMed

    Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse; Yang, Mingshi; Nielsen, Hanne Mørck; Mu, Huiling

    2015-01-01

    Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral delivery of peptide/protein drugs and to provide an overview of formulationand characterization strategies. For a better understanding of the challenges in oral delivery of peptide/protein drugs, the composition of GI fluids and the digestion processes of different kinds of excipients in the GI tract are summarized. Additionally, the paper provides an overview of recent studies on characterization of solid drug carriers for peptide/protein drugs, drug distribution in particles, drug release and stability in simulated GI fluids, as well as the absorption of peptide/protein drugs in cell-based models. The use of biorelevant media when applicable can increase the knowledge about the quality of DDS for oral protein delivery. Hopefully, the knowledge provided in this review will aid the establishment of improved biorelevant models capable of forecasting the performance of particulate DDS for oral peptide/protein delivery.

  5. Drug delivery systems for brain tumor therapy.

    PubMed

    Rautioa, Jarkko; Chikhale, Prashant J

    2004-01-01

    Brain tumors are one of the most lethal forms of cancer. They are extremely difficult to treat. Although, the rate of brain tumor incidence is relatively low, the field clearly lacks therapeutic strategies capable of overcoming barriers for effective delivery of drugs to brain tumors. Clinical failure of many potentially effective therapeutics for the treatment of brain tumors is usually not due to a lack of drug potency, but rather can be attributed to shortcomings in the methods by which a drug is delivered to the brain and into brain tumors. In response to the lack of efficacy of conventional drug delivery methods, extensive efforts have been made to develop novel strategies to overcome the obstacles for brain tumor drug delivery. The challenge is to design therapeutic strategies that deliver drugs to brain tumors in a safe and effective manner. This review provides some insight into several potential techniques that have been developed to improve drug delivery to brain tumors, and it should be helpful to clinicians and research scientists as well.

  6. Applications of chitosan nanoparticles in drug delivery.

    PubMed

    Tajmir-Riahi, H A; Nafisi, Sh; Sanyakamdhorn, S; Agudelo, D; Chanphai, P

    2014-01-01

    We have reviewed the binding affinities of several antitumor drugs doxorubicin (Dox), N-(trifluoroacetyl) doxorubicin (FDox), tamoxifen (Tam), 4-hydroxytamoxifen (4-Hydroxytam), and endoxifen (Endox) with chitosan nanoparticles of different sizes (chitosan-15, chitosan-100, and chitosan-200 KD) in order to evaluate the efficacy of chitosan nanocarriers in drug delivery systems. Spectroscopic and molecular modeling studies showed the binding sites and the stability of drug-polymer complexes. Drug-chitosan complexation occurred via hydrophobic and hydrophilic contacts as well as H-bonding network. Chitosan-100 KD was the more effective drug carrier than the chitosan-15 and chitosan-200 KD.

  7. Nanoparticles and microparticles for skin drug delivery.

    PubMed

    Prow, Tarl W; Grice, Jeffrey E; Lin, Lynlee L; Faye, Rokhaya; Butler, Margaret; Becker, Wolfgang; Wurm, Elisabeth M T; Yoong, Corinne; Robertson, Thomas A; Soyer, H Peter; Roberts, Michael S

    2011-05-30

    Skin is a widely used route of delivery for local and systemic drugs and is potentially a route for their delivery as nanoparticles. The skin provides a natural physical barrier against particle penetration, but there are opportunities to deliver therapeutic nanoparticles, especially in diseased skin and to the openings of hair follicles. Whilst nanoparticle drug delivery has been touted as an enabling technology, its potential in treating local skin and systemic diseases has yet to be realised. Most drug delivery particle technologies are based on lipid carriers, i.e. solid lipid nanoparticles and nanoemulsions of around 300 nm in diameter, which are now considered microparticles. Metal nanoparticles are now recognized for seemingly small drug-like characteristics, i.e. antimicrobial activity and skin cancer prevention. We present our unpublished clinical data on nanoparticle penetration and previously published reports that support the hypothesis that nanoparticles >10nm in diameter are unlikely to penetrate through the stratum corneum into viable human skin but will accumulate in the hair follicle openings, especially after massage. However, significant uptake does occur after damage and in certain diseased skin. Current chemistry limits both atom by atom construction of complex particulates and delineating their molecular interactions within biological systems. In this review we discuss the skin as a nanoparticle barrier, recent work in the field of nanoparticle drug delivery to the skin, and future directions currently being explored. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Lung surfactant as a drug delivery system.

    PubMed

    Vermehren, C; Frokjaer, S; Aurstad, T; Hansen, J

    2006-01-03

    Lung surfactant is a complex mixture of mainly phospholipids and proteins. The composition leads to a unique spreading effect of the surfactant as well as spontaneous vesicle formation, which may be favourable characteristics of a drug delivery system for pulmonary delivery. The aim of study was to investigate the potential use of the surfactant extract, HL10 (LeoPharma, DK) as a drug delivery system. Studies involved incorporation of hydrophilic- and amphipathic model drugs (sucrose and acylated peptides) into HL10 and elucidation of the influence of surfactant proteins on the HL10 behaviour. Results showed that HL10 vesicles did not retain sucrose indicating formation of leaky vesicles. Studying the influence of surfactant proteins on release from DPPC-liposomes showed tendencies toward a protein-induced release. Hence, the surfactant proteins may influence the membrane lipid packing and characteristics resulting in leakiness of the membranes. Incorporation of acylated peptides into HL10 depended on the chain length rendering a successful incorporation of the peptide acylated with C14-acyl chains. This study suggests that HL10 may be a promising drug delivery system for the pulmonary delivery of amphipathic drug substances, e.g. therapeutically active acylated peptides (e.g. acylated insulin).

  9. Enhancing the efficiency of thiomers: Utilizing a highly mucoadhesive polymer as backbone for thiolation and preactivation.

    PubMed

    Prüfert, Felix; Bonengel, Sonja; Menzel, Claudia; Bernkop-Schnürch, Andreas

    2017-01-01

    The objective of this study was to develop a novel thiomer with enhanced mucoadhesive properties using a highly mucoadhesive polymeric backbone. Fixomer™ A-30 (poly(methacrylic acid-co-sodium acrylamidomethyl propane sulfonate)), exhibiting a mucoadhesive strength superior to that of all other polymers, was thiolated by conjugation with l-cysteine and furthermore preactivated with 2-mercaptonicotinic acid (MNA). The resulting derivatives Fix-SH and Fix-S-MNA exhibited coupling rates of 755μmol thiol groups and 304μmol MNA per gram polymer, respectively. The mucoadhesive profile was evaluated with three different methods: tensile studies, rotating cylinder and rheological synergism. In tensile studies, a total work of adhesion of above 500μJ was determined for the unmodified polymer that increased to around 750μJ after thiolation and around 1500μJ after preactivation. The adhesion time of Fix-SH on the rotating cylinder was 3.7-fold and that of Fix-S-MNA 6.8-fold longer compared to the unmodified polymer. A rheological synergism was observed for the unmodified polymer as well as the derivatives with a non-significant difference for Fix-SH but a 5.44-fold improvement for Fix-S-MNA. Fix-S-MNA showed a significantly improved swelling behavior with a water-uptake up to the 30-fold of its initial weight over >50h whereas thiolation showed only slight improvements. Derivatization had no significant influence on cell viability. According to the results, Fix-S-MNA seems to be a suitable polymer for mucoadhesive drug delivery systems. Copyright © 2016. Published by Elsevier B.V.

  10. Trojan Microparticles for Drug Delivery

    PubMed Central

    Anton, Nicolas; Jakhmola, Anshuman; Vandamme, Thierry F.

    2012-01-01

    During the last decade, the US Food and Drug Administration (FDA) have regulated a wide range of products, (foods, cosmetics, drugs, devices, veterinary, and tobacco) which may utilize micro and nanotechnology or contain nanomaterials. Nanotechnology allows scientists to create, explore, and manipulate materials in nano-regime. Such materials have chemical, physical, and biological properties that are quite different from their bulk counterparts. For pharmaceutical applications and in order to improve their administration (oral, pulmonary and dermal), the nanocarriers can be spread into microparticles. These supramolecular associations can also modulate the kinetic releases of drugs entrapped in the nanoparticles. Different strategies to produce these hybrid particles and to optimize the release kinetics of encapsulated drugs are discussed in this review. PMID:24300177

  11. Functional Cyclodextrin Polyrotaxanes for Drug Delivery

    NASA Astrophysics Data System (ADS)

    Yui, Nobuhiko; Katoono, Ryo; Yamashita, Atsushi

    The mobility of cyclodextrins (CDs) threaded onto a linear polymeric chain and the dethreading of the CDs from the chain are the most fascinating features seen in polyrotaxanes. These structural characteristics are very promising for their possible applications in drug delivery. Enhanced multivalent interaction between ligand-receptor systems by using ligand-conjugated polyrotaxanes would be just one of the excellent properties related to the CD mobility. Gene delivery using cytocleavable polyrotaxanes is a more practical but highly crucial issue in drug delivery. Complexation of the polyrotaxanes with DNA and its intracellular DNA release ingeniously utilizes both CD mobility and polyrotaxane dissociation to achieve effective gene delivery. Such a supramolecular approach using CD-containing polyrotaxanes is expected to exploit a new paradigm of biomaterials.

  12. Formulation and in-vitro efficacy of antifungal mucoadhesive polymeric matrices for the delivery of miconazole nitrate.

    PubMed

    Tejada, G; Piccirilli, G N; Sortino, M; Salomón, C J; Lamas, M C; Leonardi, D

    2017-10-01

    Oral candidiasis is the most common opportunistic infection affecting patients with the human immunodeficiency virus. Miconazole buccal tablets or miconazole gel are approved for the treatment of oropharyngeal candidiasis. However, buccal films present more flexibility and also offer protection for the wounded mucosa, reducing pain. Due to their small size and thickness, buccal films may improve patients' compliance, compared to tablets. Additionally, they may increase the relatively short residence time on the mucosa of oral gels, which are easily removed by saliva. Polymeric films loaded with miconazole nitrate were prepared by a casting/solvent evaporation methodology using chitosan, carbopol, gelatin, gum arabic, and alginate to form the polymeric matrices. The morphology of films was investigated by scanning electron microscopy; interactions between polymers were analyzed by infrared spectroscopy and drug crystallinity by differential thermal analysis and X-ray diffraction. Films were characterized in terms of thickness, folding endurance, tensile properties, swelling, adhesiveness, and drug release. Finally, the antifungal activity against cultures of the five most important fungal opportunistic pathogens belonging to Candida genus was investigated. The more appropriate formulations were those based on chitosan-gelatin and chitosan-carbopol which showed good mechanical properties and adhesiveness, a relative low swelling index, improved drug release, and showed better in vitro activity against Candida cultures than miconazole nitrate raw material. Thus, it will be possible to produce a new pharmaceutical form based on polymeric films containing chitosan and miconazole nitrate, which could be loaded with low drug concentration producing the same therapeutic effect against Candida cultures. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Engineered Polymers for Advanced Drug Delivery

    PubMed Central

    Kim, Sungwon; Kim, Jong-Ho; Jeon, Oju; Kwon, Ick Chan; Park, Kinam

    2009-01-01

    Engineered polymers have been utilized for developing advanced drug delivery systems. The development of such polymers has caused advances in polymer chemistry, which, in turn, has resulted in smart polymers that can respond to changes in environmental condition, such as temperature, pH, and biomolecules. The responses vary widely from swelling/deswelling to degradation. Drug-polymer conjugates and drug-containing nano/micro-particles have been used for drug targeting. Engineered polymers and polymeric systems have also been used in new areas, such as molecular imaging as well as in nanotechnology. This review examines the engineered polymers that have been used as traditional drug delivery and as more recent applications in nanotechnology. PMID:18977434

  14. Nanoparticles and nanofibers for topical drug delivery

    PubMed Central

    Goyal, Ritu; Macri, Lauren K.; Kaplan, Hilton M.; Kohn, Joachim

    2016-01-01

    This review provides the first comprehensive overview of the use of both nanoparticles and nanofibers for topical drug delivery. Researchers have explored the use of nanotechnology, specifically nanoparticles and nanofibers, as drug delivery systems for topical and transdermal applications. This approach employs increased drug concentration in the carrier, in order to increase drug flux into and through the skin. Both nanoparticles and nanofibers can be used to deliver hydrophobic and hydrophilic drugs and are capable of controlled release for a prolonged period of time. The examples presented provide significant evidence that this area of research has—and will continue to have — a profound impact on both clinical outcomes and the development of new products. PMID:26518723

  15. Genetically engineered nanocarriers for drug delivery

    PubMed Central

    Shi, Pu; Gustafson, Joshua A; MacKay, J Andrew

    2014-01-01

    Cytotoxicity, low water solubility, rapid clearance from circulation, and off-target side-effects are common drawbacks of conventional small-molecule drugs. To overcome these shortcomings, many multifunctional nanocarriers have been proposed to enhance drug delivery. In concept, multifunctional nanoparticles might carry multiple agents, control release rate, biodegrade, and utilize target-mediated drug delivery; however, the design of these particles presents many challenges at the stage of pharmaceutical development. An emerging solution to improve control over these particles is to turn to genetic engineering. Genetically engineered nanocarriers are precisely controlled in size and structure and can provide specific control over sites for chemical attachment of drugs. Genetically engineered drug carriers that assemble nanostructures including nanoparticles and nanofibers can be polymeric or non-polymeric. This review summarizes the recent development of applications in drug and gene delivery utilizing nanostructures of polymeric genetically engineered drug carriers such as elastin-like polypeptides, silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric genetically engineered drug carriers such as vault proteins and viral proteins. PMID:24741309

  16. Nanoparticles in the ocular drug delivery

    PubMed Central

    Zhou, Hong-Yan; Hao, Ji-Long; Wang, Shuang; Zheng, Yu; Zhang, Wen-Song

    2013-01-01

    Ocular drug transport barriers pose a challenge for drug delivery comprising the ocular surface epithelium, the tear film and internal barriers of the blood-aqueous and blood-retina barriers. Ocular drug delivery efficiency depends on the barriers and the clearance from the choroidal, conjunctival vessels and lymphatic. Traditional drug administration reduces the clinical efficacy especially for poor water soluble molecules and for the posterior segment of the eye. Nanoparticles (NPs) have been designed to overcome the barriers, increase the drug penetration at the target site and prolong the drug levels by few internals of drug administrations in lower doses without any toxicity compared to the conventional eye drops. With the aid of high specificity and multifunctionality, DNA NPs can be resulted in higher transfection efficiency for gene therapy. NPs could target at cornea, retina and choroid by surficial applications and intravitreal injection. This review is concerned with recent findings and applications of NPs drug delivery systems for the treatment of different eye diseases. PMID:23826539

  17. Liposomes as delivery systems for antineoplastic drugs

    NASA Astrophysics Data System (ADS)

    Medina, Luis Alberto

    2014-11-01

    Liposome drug formulations are defined as pharmaceutical products containing active drug substances encapsulated within the lipid bilayer or in the interior aqueous space of the liposomes. The main importance of this drug delivery system is based on its drastic reduction in systemic dose and concomitant systemic toxicity that in comparison with the free drug, results in an improvement of patient compliance and in a more effective treatment. There are several therapeutic drugs that are potential candidates to be encapsulated into liposomes; particular interest has been focused in therapeutic and antineoplastic drugs, which are characterized for its low therapeutic index and high systemic toxicity. The use of liposomes as drug carriers has been extensively justified and the importance of the development of different formulations or techniques to encapsulate therapeutic drugs has an enormous value in benefit of patients affected by neoplastic diseases.

  18. Barriers to drug delivery in solid tumors

    PubMed Central

    Sriraman, Shravan Kumar; Aryasomayajula, Bhawani; Torchilin, Vladimir P

    2014-01-01

    Over the last decade, significant progress has been made in the field of drug delivery. The advent of engineered nanoparticles has allowed us to circumvent the initial limitations to drug delivery such as pharmacokinetics and solubility. However, in spite of significant advances to tumor targeting, an effective treatment strategy for malignant tumors still remains elusive. Tumors possess distinct physiological features which allow them to resist traditional treatment approaches. This combined with the complexity of the biological system presents significant hurdles to the site-specific delivery of therapeutic drugs. One of the key features of engineered nanoparticles is that these can be tailored to execute specific functions. With this review, we hope to provide the reader with a clear understanding and knowledge of biological barriers and the methods to exploit these characteristics to design multifunctional nanocarriers, effect useful dosing regimens and subsequently improve therapeutic outcomes in the clinic. PMID:25068098

  19. Collagen-coated microparticles in drug delivery.

    PubMed

    Sehgal, Praveen Kumar; Srinivasan, Aishwarya

    2009-07-01

    Advantages of drug-incorporated collagen particles have been described for the controlled delivery system for therapeutic actions. The attractiveness of collagen lies in its low immunogenicity and high biocompatibility. It is also recognized by the body as a natural constituent rather than a foreign body. Our research and development efforts are focused towards addressing some of the limitations of collagen, like the high viscosity of an aqueous phase, nondissolution in neutral pH buffers, thermal instability (denaturation) and biodegradability, to make it an ideal material for drug delivery with particular reference to microparticles. These limitations could be overcome by making collagen conjugates with other biomaterials or chemically modifying collagen monomer without affecting its triple helical conformation and maintaining its native properties. This article highlights collagen microparticles' present status as a carrier in drug delivery.

  20. Functional physico-chemical, ex vivo permeation and cell viability characterization of omeprazole loaded buccal films for paediatric drug delivery.

    PubMed

    Khan, Sajjad; Trivedi, Vivek; Boateng, Joshua

    2016-03-16

    Buccal films were prepared from aqueous and ethanolic Metolose gels using the solvent casting approach (40°C). The hydration (PBS and simulated saliva), mucoadhesion, physical stability (20°C, 40°C), in vitro drug (omeprazole) dissolution (PBS and simulated saliva), ex vivo permeation (pig buccal mucosa) in the presence of simulated saliva, ex vivo bioadhesion and cell viability using MTT of films were investigated. Hydration and mucoadhesion results showed that swelling capacity and adhesion was higher in the presence of PBS than simulated saliva (SS) due to differences in ionic strength. Omeprazole was more stable at 20°C than 40°C whilst omeprazole release reached a plateau within 1h and faster in PBS than in SS. Fitting release data to kinetic models showed that Korsmeyer-Peppas equation best fit the dissolution data. Drug release in PBS was best described by zero order via non-Fickian diffusion but followed super case II transport in SS attributed to drug diffusion and polymer erosion. The amount of omeprazole permeating over 2h was 275 ug/cm(2) whilst the formulations and starting materials showed cell viability values greater than 95%, confirming their safety for potential use in paediatric buccal delivery.

  1. Ultrasound-mediated gastrointestinal drug delivery.

    PubMed

    Schoellhammer, Carl M; Schroeder, Avi; Maa, Ruby; Lauwers, Gregory Yves; Swiston, Albert; Zervas, Michael; Barman, Ross; DiCiccio, Angela M; Brugge, William R; Anderson, Daniel G; Blankschtein, Daniel; Langer, Robert; Traverso, Giovanni

    2015-10-21

    There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn's and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease.

  2. Ultrasound-mediated gastrointestinal drug delivery

    PubMed Central

    Schoellhammer, Carl M.; Schroeder, Avi; Maa, Ruby; Lauwers, Gregory Yves; Swiston, Albert; Zervas, Michael; Barman, Ross; DiCiccio, Angela M.; Brugge, William R.; Anderson, Daniel G.; Blankschtein, Daniel; Langer, Robert; Traverso, Giovanni

    2016-01-01

    There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn’s and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease. PMID:26491078

  3. Floating-mucoadhesive beads of clarithromycin for the treatment of Helicobacter pylori infection.

    PubMed

    Gattani, Surendra Ganeshlal; Savaliya, Pankaj Jayantilal; Belgamwar, Veena Shailendra

    2010-06-01

    An objective of the present study was to develop alginate/hydroxypropyl methylcellulose (HPMC) based floating-mucoadhesive beads of clarithromycin to provide prolonged contact time of antibiotic to treat stomach ulcer. Floating-mucoadhesive beads were prepared and characterized for in vitro performance followed by investigation of ex vivo study in albino-wistar rats. Beads were prepared by ionic gelation technique where calcium chloride used as gelating agent and incorporated liquid paraffin for floating of the beads. Prepared beads were evaluated extensively for particle size, drug entrapment; swelling and surface morphology by using scanning electron microscopy. X-ray radioimaging study in rabbits, in vitro mucoadhesion using rat stomach mucosal membrane and in vitro drug release studies were carried out. Ex vivo performance of alginate-HPMC beads were studied using albino rats in comparison to simple alginate-calcium beads. Alginate-HPMC beads may be suitable floating-muco-adhesive drug delivery system for delivering clarithromycin to treat stomach ulcers.

  4. Carvedilol-loaded nanocapsules: Mucoadhesive properties and permeability across the sublingual mucosa.

    PubMed

    Chaves, Paula Dos Santos; Ourique, Aline Ferreira; Frank, Luiza Abrahão; Pohlmann, Adriana Raffin; Guterres, Sílvia Stanisçuaski; Beck, Ruy Carlos Ruver

    2017-05-01

    Carvedilol is a drug used to treat heart failure, hypertension, and coronary artery diseases . However, it has low oral bioavailability (25-35%) due to its high first-pass hepatic metabolism. The objective of this study was to develop carvedilol-loaded mucoadhesive nanocapsules as delivery systems for the sublingual administration of the drug. Nanocapsules were prepared using poly(ε-caprolactone) (CAR-LNC) and Eudragit® RS 100 (CAR-NC) as polymeric wall. In vitro interaction of formulations with mucin was performed to predict their mucoadhesion capacity. The permeability and washability profiles of carvedilol were evaluated using porcine sublingual mucosa. The mean diameter of particles in formulations was in the nanometric range, and particles had low polydispersity and slightly acidic pH. Zeta potential values were positive for CAR-NC and negative for CAR-LNC. Encapsulation efficiency was higher than 87% and 99% for CAR-NC and CAR-LNC, respectively. Both formulations presented controlled drug release profiles and mucoadhesive properties. Carvedilol was able to permeate through the sublingual mucosa. Nanoencapsulation improved retention time on the mucosa and permeation in presence of simulated salivary flux. This study highlighted the suitability of using CAR-loaded nanocapsules in the development of innovative sublingual dosage forms.

  5. Local Drug Delivery to Prevent Restenosis

    PubMed Central

    Seedial, Stephen M.; Ghosh, Soumojit; Saunders, R. Scott; Suwanabol, Pasithorn A.; Shi, Xudong; Liu, Bo; Kent, K. Craig

    2013-01-01

    Introduction Despite significant advances in vascular biology, bioengineering and pharmacology, restenosis remains a limitation to the overall efficacy of vascular reconstructions, both percutaneous and open. Although the pathophysiology of intimal hyperplasia is complex, a number of drugs and/or molecular tools have been identified that can prevent restenosis. Moreover, the focal nature of this process lends itself to treatment with local drug administration. In this article we provide a broad overview of current and future techniques for local drug delivery that have been developed to prevent restenosis following vascular intervention. Methods A systematic electronic literature search using PubMed was performed for all accessible published articles through September 2012. In an effort to remain current, additional searches were performed for abstracts presented at relevant societal meetings, filed patents, clinical trials and funded NIH awards. Results The efficacy of local drug delivery has been demonstrated in the coronary circulation with the current clinical use of drug-eluting stents (DES). Until recently, however, DES were not found to be efficacious in the peripheral circulation. Further pursuit of intraluminal devices has led to the development of balloon-based technologies with a recent surge in trials involving drug-eluting balloons. Early data appears encouraging, particularly for treatment of lesions in the superficial femoral artery, with several devices having recently received the CE mark in Europe. Investigators have also explored periadventitial application of biomaterials containing anti-restenotic drugs, an approach that could be particularly useful for surgical bypass or endarterectomy. In the past systemic drug delivery has been unsuccessful, however, there has been recent exploration of intravenous delivery of drugs designed specifically to target injured or reconstructed arteries. Our review revealed a multitude of additional interesting

  6. Ultrasonic drug delivery--a general review.

    PubMed

    Pitt, William G; Husseini, Ghaleb A; Staples, Bryant J

    2004-11-01

    Ultrasound has an ever-increasing role in the delivery of therapeutic agents, including genetic material, protein and chemotherapeutic agents. Cavitating gas bodies, such as microbubbles, are the mediators through which the energy of relatively non-interactive pressure waves is concentrated to produce forces that permeabilise cell membranes and disrupt the vesicles that carry drugs. Thus, the presence of microbubbles enormously enhances ultrasonic delivery of genetic material, proteins and smaller chemical agents. Numerous reports show that the most efficient delivery of genetic material occurs in the presence of cavitating microbubbles. Attaching the DNA directly to the microbubbles, or to gas-containing liposomes, enhances gene uptake even further. Ultrasonic-enhanced gene delivery has been studied in various tissues, including cardiac, vascular, skeletal muscle, tumour and even fetal tissue. Ultrasonic-assisted delivery of proteins has found most application in transdermal transport of insulin. Cavitation events reversibly disrupt the structure of the stratus corneum to allow transport of these large molecules. Other hormones and small proteins could also be delivered transdermally. Small chemotherapeutic molecules are delivered in research settings from micelles and liposomes exposed to ultrasound. Cavitation appears to play two roles: it disrupts the structure of the carrier vesicle and releases the drug; and makes cell membranes and capillaries more permeable to drugs. There remains a need to better understand the physics of cavitation of microbubbles and the impact that such cavitation has on cells and drug-carrying vesicles.

  7. Light induced drug delivery into cancer cells.

    PubMed

    Shamay, Yosi; Adar, Lily; Ashkenasy, Gonen; David, Ayelet

    2011-02-01

    Cell-penetrating peptides (CPPs) can be used for intracellular delivery of a broad variety of cargoes, including various nanoparticulate pharmaceutical carriers. However, the cationic nature of all CPP sequences, and thus lack of cell specificity, limits their in vivo use for drug delivery applications. Here, we have devised and tested a strategy for site-specific delivery of dyes and drugs into cancer cells by using polymers bearing a light activated caged CPP (cCPP). The positive charge of Lys residues on the minimum sequence of the CPP penetratin ((52)RRMKWKK(58)) was masked with photo-cleavable groups to minimize non-specific adsorption and cellular uptake. Once illuminated by UV light, these protecting groups were cleaved, the positively charged CPP regained its activity and facilitated rapid intracellular delivery of the polymer-dye or polymer-drug conjugates into cancer cells. We have found that a 10-min light illumination time was sufficient to enhance the penetration of the polymer-CPP conjugates bearing the proapoptotic peptide, (D)(KLAKLAK)(2), into 80% of the target cells, and to promote a 'switch' like cytotoxic activity resulting a shift from 100% to 10% in cell viability after 2 h. This report provides an example for tumor targeting by means of light activation of cell-penetrating peptides for intracellular drug delivery.

  8. Transungual drug delivery: current status.

    PubMed

    Elkeeb, Rania; AliKhan, Ali; Elkeeb, Laila; Hui, Xiaoying; Maibach, Howard I

    2010-01-15

    Topical therapy is highly desirable in treating nail disorders due to its localized effects, which results in minimal adverse systemic events and possibly improved adherence. However, the effectiveness of topical therapies is limited by minimal drug permeability through the nail plate. Current research on nail permeation that focuses on altering the nail plate barrier by means of chemical treatments, penetration enhancers as well as physical and mechanical methods is reviewed. A new method of nail sampling is examined. Finally limitations of current ungual drug permeability studies are briefly discussed.

  9. Mucoadhesive glycol chitosan nanoparticles for intranasal delivery of hepatitis B vaccine: enhancement of mucosal and systemic immune response.

    PubMed

    Pawar, Dilip; Jaganathan, K S

    2016-01-01

    In this study, for the first time, glycol chitosan (GC) nanoparticles (NPs) were prepared and evaluated to obtain systemic and mucosal immune responses against nasally administered hepatitis B surface antigen (HBsAg). Size, zeta potential and morphology of the NPs were investigated as a function of preparation method. NPs with high loading efficacy ( > 95%) and positively charged surface were obtained with an average particle size of approximately 200 nm. The structural integrity of HBsAg in NPs was evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis and further confirmed by measuring the in vitro antigenicity using an enzyme immunoassay. During in vivo studies, GC NPs showed the lowest nasal clearance rate and better mucosal uptake when compared with chitosan (CS) NPs. The immunogenicity of NPs-based delivery system(s) was assessed by measuring anti-HBsAg antibody titer in mice serum and secretions after intranasal administration. The alum-based HBsAg vaccine injected subcutaneously was used as positive control. Results indicated that alum-based HBsAg induced strong humoral but negligible mucosal immunity. However, GC NPs induced stronger immune response at both of the fronts as compared to generated by CS NPs. This study demonstrates that this newly developed system has potential for mucosal administration of vaccines.

  10. Water quantitatively induces the mucoadhesion of liquid crystalline phases of glyceryl monooleate.

    PubMed

    Lee, J; Young, S A; Kellaway, I W

    2001-05-01

    The possible role of water in the mucoadhesion phenomenon exhibited by the liquid crystalline phases of glyceryl monooleate was investigated using an in-vitro tensile strength technique. The mucoadhesion of the liquid crystalline phases of glyceryl monooleate was found to occur following uptake of water. The mucoadhesive force of the cubic phase was consistent since it is not capable of taking up additional water. An increase in pre-load period greatly facilitated the mucoadhesion of glyceryl monooleate (0% w/w initial water content), suggesting that the mucoadhesion is dependent upon the extent of the dehydration of the substrate. A good linear relationship between initial water content of the liquid crystalline phases and mucoadhesive force led to the conclusion that the mucoadhesive force increased with decreasing initial water concentration. Rheological properties of the liquid crystalline phases were also studied to allow a correlation between physical changes and mucoadhesion of the liquid crystalline phases, revealing that higher water concentrations in the liquid crystalline phases led to a more ordered structure that showed less mucoadhesion. The results of this study indicated that the mucoadhesive force of the liquid crystalline phases of glyceryl monooleate is determined by the capability to take up water from a water-rich environment. It may, therefore, be advantageous to use the lamellar phase as a buccal drug carrier as opposed to the relatively less mucoadhesive cubic phase.

  11. Zwitterionic drug nanocarriers: a biomimetic strategy for drug delivery.

    PubMed

    Jin, Qiao; Chen, Yangjun; Wang, Yin; Ji, Jian

    2014-12-01

    Nanomaterials self-assembled from amphiphilic functional copolymers have emerged as safe and efficient nanocarriers for delivery of therapeutics. Surface engineering of the nanocarriers is extremely important for the design of drug delivery systems. Bioinspired zwitterions are considered as novel nonfouling materials to construct biocompatible and bioinert nanocarriers. As an alternative to poly(ethylene glycol) (PEG), zwitterions exhibit some unique properties that PEG do not have. In this review, we highlight recent progress of the design of drug nanocarriers using a zwitterionic strategy. The possible mechanism of stealth properties of zwitterions was proposed. The advantages of zwitterionic drug nanocarriers deriving from phosphorylcholine (PC), carboxybetaine (CB), and sulfobetaine (SB) are also discussed.

  12. Carboxymethyl chitosan/phospholipid bilayer-capped mesoporous carbon nanoparticles with pH-responsive and prolonged release properties for oral delivery of the antitumor drug, Docetaxel.

    PubMed

    Zhang, Yanzhuo; Zhu, Wufu; Zhang, Heran; Han, Jin; Zhang, Lihua; Lin, Qisi; Ai, Fengwei

    2017-09-10

    In this article, a new type of carboxymethyl chitosan/phospholipid bilayer-capped mesoporous carbon nanomatrix (CCS/PL/MC) was fabricated as a potential nano-drug delivery system. In this drug delivery system, a mesoporous carbon nanomatrix (MC) acts as the support for loading drug molecules, a positively charged phospholipid (PL) layer works as the inner shell for prolonged drug release and a negatively charged carboxymethyl chitosan (CCS) layer serves as the outer shell for pH-responsive drug release. Docetaxel (DTX) was selected as a model drug. The drug-loaded CCS/PL/MC was synthesized via a combination approach of double emulsion/solvent evaporation followed by lyophilization. The drug-loaded nanoparticles were characterized for their particle size, structure, morphology, zeta (ζ)-potential, specific surface area, porosity, drug loading and solid state. In vitro drug release tests showed that the drug-loaded CCS/PL/MC nanoparticles possess a good pH-sensitivity and prolonged releasing ability with negligible release in gastric media and controlled release in intestinal media. Compared with MC and PL-capped MC, CCS/PL/MC had a greater mucoadhesiveness. Moreover, cellular uptake study indicated that CCS/PL/MC might improve intracellular drug delivery. These results suggest that this hybrid nanocarrier, combining the beneficial features of CCS, PL and MC, is a promising drug delivery system able to improve the oral absorption of antitumor drugs. Copyright © 2017. Published by Elsevier B.V.

  13. Plasmon resonant liposomes for controlled drug delivery

    NASA Astrophysics Data System (ADS)

    Knights-Mitchell, Shellie S.; Romanowski, Marek

    2015-03-01

    Nanotechnology use in drug delivery promotes a reduction in systemic toxicity, improved pharmacokinetics, and better drug bioavailability. Liposomes continue to be extensively researched as drug delivery systems (DDS) with formulations such as Doxil® and Ambisome® approved by FDA and successfully marketed in the United States. However, the limited ability to precisely control release of active ingredients from these vesicles continues to challenge the broad implementation of this technology. Moreover, the full potential of the carrier to sequester drugs until it can reach its intended target has yet to be realized. Here, we describe a liposomal DDS that releases therapeutic doses of an anticancer drug in response to external stimulus. Earlier, we introduced degradable plasmon resonant liposomes. These constructs, obtained by reducing gold on the liposome surface, facilitate spatial and temporal release of drugs upon laser light illumination that ultimately induces an increase in temperature. In this work, plasmon resonant liposomes have been developed to stably encapsulate and retain doxorubicin at physiological conditions represented by isotonic saline at 37o C and pH 7.4. Subsequently, they are stimulated to release contents either by a 5o C increase in temperature or by laser illumination (760 nm and 88 mW/cm2 power density). Successful development of degradable plasmon resonant liposomes responsive to near-infrared light or moderate hyperthermia can provide a new delivery method for multiple lipophilic and hydrophilic drugs with pharmacokinetic profiles that limit clinical utility.

  14. Drug delivery system and breast cancer cells

    NASA Astrophysics Data System (ADS)

    Colone, Marisa; Kaliappan, Subramanian; Calcabrini, Annarica; Tortora, Mariarosaria; Cavalieri, Francesca; Stringaro, Annarita

    2016-06-01

    Recently, nanomedicine has received increasing attention for its ability to improve the efficacy of cancer therapeutics. Nanosized polymer therapeutic agents offer the advantage of prolonged circulation in the blood stream, targeting to specific sites, improved efficacy and reduced side effects. In this way, local, controlled delivery of the drug will be achieved with the advantage of a high concentration of drug release at the target site while keeping the systemic concentration of the drug low, thus reducing side effects due to bioaccumulation. Various drug delivery systems such as nanoparticles, liposomes, microparticles and implants have been demonstrated to significantly enhance the preventive/therapeutic efficacy of many drugs by increasing their bioavailability and targetability. As these carriers significantly increase the therapeutic effect of drugs, their administration would become less cost effective in the near future. The purpose of our research work is to develop a delivery system for breast cancer cells using a microvector of drugs. These results highlight the potential uses of these responsive platforms suited for biomedical and pharmaceutical applications. At the request of all authors of the paper an updated version was published on 12 July 2016. The manuscript was prepared and submitted without Dr. Francesca Cavalieri's contribution and her name was added without her consent. Her name has been removed in the updated and re-published article.

  15. Tuberculosis chemotherapy: current drug delivery approaches

    PubMed Central

    du Toit, Lisa Claire; Pillay, Viness; Danckwerts, Michael Paul

    2006-01-01

    Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance. PMID:16984627

  16. Maximized mucoadhesion and skin permeation of anti-AIDS-loaded niosomal gels.

    PubMed

    Zidan, Ahmed S; Habib, Muhammad J

    2014-03-01

    The low permeability of the anti-AIDS, tenofovir, limits its antiretroviral clinical potency. The proposed study aimed at assessing the critical biological responses of tenofovir through the development and optimization of its surfactant-based niosomal gels intended for vaginal delivery. Fatty acid chain length of the amphiphile and cholesterol loading were optimized using a 3² full factorial design. Vesicular size, shape and surface charge, drug entrapment efficiency, in vitro release, and skin permeation were used to assess the gels. In addition, their biological performance on Lactobacillus crispatus viability and mucoadhesion to porcine vaginal tissue was also assessed. Within the design space, mucoadhesion percentage ranged from 6.2% to 28.6% and increased nonlinearly by decreasing niosomal vesicular size and linearly by increasing surface charge. Moreover, these gels were not cytotoxic to Lactobacillus crispatus for 48 h. For maximizing tenofovir entrapment, percutaneous permeation, and mucoadhesion while achieving sustained-release features, an optimum formulation was proposed with the shortest length of fatty chain and 0.48 mM cholesterol content. Overall, applying quality by design paradigm to the development of tenofovir niosomal gels not only offered a promising nanomedicine for the vaginal microbicide delivery but also unveiled the critical formulation interactions influencing its biological performance.

  17. Semi-Interpenetrating Network (sIPN) Gelatin Nanofiber Scaffolds for Oral Mucosal Drug Delivery

    PubMed Central

    Aduba, Donald C.; Hammer, Jeremy A.; Yuan, Quan; Yeudall, W. Andrew; Bowlin, Gary L.; Yang, Hu

    2013-01-01

    The oral mucosa is a promising absorption site for drug administration because it is permeable, highly vascularized and allows for ease of administration. Nanofiber scaffolds for local or systemic drug delivery through the oral mucosa, however, have not been fully explored. In this work, we fabricated electrospun gelatin nanofiber scaffolds for oral mucosal drug delivery. To improve structural stability of the electrospun gelatin scaffolds and allow non-invasive incorporation of therapeutics into the scaffold, we employed photo-reactive polyethylene glycol diacrylate (PEG-DA575, 575 gmol−1) as a cross-linker to stabilize the scaffold by forming semi-interpenetrating network gelatin nanofiber scaffolds (sIPN NSs), during which cross-linker concentration was varied (1X, 2X, 4X, and 8X). The results showed that electrospun gelatin nanofiber scaffolds after being cross-linked with PEG-DA575 (i.e., sIPN NS1X, 2X, 4X, and 8X) retained fiber morphology and possessed improved structural stability. A series of structural parameters and properties of the cross-linked electrospun gelatin scaffolds were systematically characterized in terms of morphology, fiber diameter, mechanical properties, porosity, swelling and degradation. Mucin absorption onto sIPN NS4X was also confirmed, indicating this scaffold possessed greatest mucoadhesion properties among those tested. Slow release of nystatin, an anti-fungal reagent, from the sIPN gelatin nanofiber scaffold was demonstrated. PMID:23416578

  18. Ingestion of drugs by "parachuting": a unique drug delivery technique.

    PubMed

    Kenerson, Katherine L; Lear-Kaul, Kelly C

    2012-06-01

    "Parachuting" is a technique of drug delivery where medications or illicit drugs are ingested by wrapping the drug of choice in a covering, which then will dissolve or unravel in the gastrointestinal tract, thereby releasing the drug for absorption. Parachuting of drugs can entail crushing of a pill prior to packaging to theoretically increase the surface area for absorption or may involve the packaging of a higher than usual dose of a drug in attempts to attain a sustained-release effect as the "parachute" dissolves or unravels. A case is presented in which a prescription drug abuser known to parachute his medications dies from obstruction of his airway by the inhaled packet. Risks of parachuting any drug would include overdose and fatal toxic effect from the drug itself and adverse effects from the packaging including bowel obstruction or perforation, or airway obstruction.

  19. Drug delivery applications with ethosomes.

    PubMed

    Ainbinder, D; Paolino, D; Fresta, M; Touitou, E

    2010-10-01

    Ethosomes are specially tailored vesicular carriers able to efficiently deliver various molecules with different physicochemical properties into deep skin layers and across the skin. This paper reviews the unique characteristics of the ethosomal carriers, focusing on work carried out with drug containing ethosomal systems in animal models and in clinical studies. The paper concludes with a discussion on the safety of the ethosomal system applications.

  20. Intracranial drug delivery for subarachnoid hemorrhage.

    PubMed

    Macdonald, Robert Loch; Leung, Ming; Tice, Tom

    2012-01-01

    Tice and colleagues pioneered site-specific, sustained-release drug delivery to the brain almost 30 years ago. Currently there is one drug approved for use in this manner. Clinical trials in subarachnoid hemorrhage have led to approval of nimodipine for oral and intravenous use, but other drugs, such as clazosentan, hydroxymethylglutaryl CoA reductase inhibitors (statins) and magnesium, have not shown consistent clinical efficacy. We propose that intracranial delivery of drugs such as nimodipine, formulated in sustained-release preparations, are good candidates for improving outcome after subarachnoid hemorrhage because they can be administered to patients that are already undergoing surgery and who have a self-limited condition from which full recovery is possible.

  1. Biodegradable Hybrid Stomatocyte Nanomotors for Drug Delivery.

    PubMed

    Tu, Yingfeng; Peng, Fei; André, Alain A M; Men, Yongjun; Srinivas, Mangala; Wilson, Daniela A

    2017-02-28

    We report the self-assembly of a biodegradable platinum nanoparticle-loaded stomatocyte nanomotor containing both PEG-b-PCL and PEG-b-PS as a potential candidate for anticancer drug delivery. Well-defined stomatocyte structures could be formed even after incorporation of 50% PEG-b-PCL polymer. Demixing of the two polymers was expected at high percentage of semicrystalline poly(ε-caprolactone) (PCL), resulting in PCL domain formation onto the membrane due to different properties of two polymers. The biodegradable motor system was further shown to move directionally with speeds up to 39 μm/s by converting chemical fuel, hydrogen peroxide, into mechanical motion as well as rapidly delivering the drug to the targeted cancer cell. Uptake by cancer cells and fast doxorubicin drug release was demonstrated during the degradation of the motor system. Such biodegradable nanomotors provide a convenient and efficient platform for the delivery and controlled release of therapeutic drugs.

  2. Biodegradable Hybrid Stomatocyte Nanomotors for Drug Delivery

    PubMed Central

    2017-01-01

    We report the self-assembly of a biodegradable platinum nanoparticle-loaded stomatocyte nanomotor containing both PEG-b-PCL and PEG-b-PS as a potential candidate for anticancer drug delivery. Well-defined stomatocyte structures could be formed even after incorporation of 50% PEG-b-PCL polymer. Demixing of the two polymers was expected at high percentage of semicrystalline poly(ε-caprolactone) (PCL), resulting in PCL domain formation onto the membrane due to different properties of two polymers. The biodegradable motor system was further shown to move directionally with speeds up to 39 μm/s by converting chemical fuel, hydrogen peroxide, into mechanical motion as well as rapidly delivering the drug to the targeted cancer cell. Uptake by cancer cells and fast doxorubicin drug release was demonstrated during the degradation of the motor system. Such biodegradable nanomotors provide a convenient and efficient platform for the delivery and controlled release of therapeutic drugs. PMID:28187254

  3. Preparation and pharmaceutical evaluation of glibenclamide slow release mucoadhesive buccal film

    PubMed Central

    Bahri-Najafi, R.; Tavakoli, N.; Senemar, M.; Peikanpour, M.

    2014-01-01

    Buccal mucoadhesive systems among novel drug delivery systems have attracted great attention in recent years due to their ability to adhere and remain on the oral mucosa and to release their drug content gradually. Buccal mucoadhesive films can improve the drug therapeutic effect by enhancement of drug absorption through oral mucosa increasing the drug bioavailability via reducing the hepatic first pass effect. The aim of the current study was to formulate the drug as buccal bioadhesive film, which releases the drug at sufficient concentration with a sustain manner reducing the frequency of the dosage form administration. One of the advantagees of this formulation is better patient compliances due to the ease of administration with no water to swallow the product. The mucoadhesive films of glibenclamide were prepared using hydroxypropyl methylcellulose (HPMC) K4M, K15M and Eudragit RL100 polymers and propylene glycol as plasticizer and co-solvent. Films were prepared using solvent casting method, and were evaluated with regard to drug content, thickness, weight variations, swelling index, tensile strength, ex vivo adhesion force and percentage of in vitro drug release. Films with high concentrations of HPMC K4M and K15M did not have favorable appearance and uniformity. The formulations prepared from Eudragit were transparent, uniform, flexible, and without bubble. The highest and the lowest percentages of swelling were observed for the films containing HPMC K15M and Eudragit RL100, respectively. Films made of HPMC K15M had adhesion force higher than those containing Eudragit RL100. Formulations with Eudragit RL100 showed the highest mean dissolution time (MDT). Drug release kinetics of all formulations followed Higuchi's model and the mechanism of diffusion was considered non-Fickian type. It was concluded that formulations containing Eudragit RL100 were more favorable than others with regard to uniformity, flexibility, rate and percentage of drug release. PMID

  4. Vaginal drug delivery systems for HIV prevention.

    PubMed

    Rohan, Lisa Cencia; Sassi, Alexandra B

    2009-03-01

    Microbicides have become a principal focus for HIV prevention strategies. The successful design of drug delivery systems for vaginal microbicide drug candidates brings with it a multitude of challenges. It is imperative that the chemical and physical characteristics of the drug candidate and its mechanism of action be clearly understood and considered to successfully deliver and target drug candidates efficiently. In addition, an understanding of the dynamic nature of the vaginal environment, the tissue and innate barriers present, as well as patient preferences are critical considerations in the design of effective microbicide products. Although the majority of drug candidates clinically evaluated to date have been delivered using conventional semisolid aqueous-based gel dosage forms, drug delivery system design has recently been extended to include advanced delivery systems such as vaginal rings, quick-dissolve films, and tablets. Ultimately, it may be necessary to develop multiple dosage platforms for a single active agent to provide users with options that can be used within the constraints of their social environment, personal choice, and environmental conditions.

  5. Optically generated ultrasound for enhanced drug delivery

    DOEpatents

    Visuri, Steven R.; Campbell, Heather L.; Da Silva, Luiz

    2002-01-01

    High frequency acoustic waves, analogous to ultrasound, can enhance the delivery of therapeutic compounds into cells. The compounds delivered may be chemotherapeutic drugs, antibiotics, photodynamic drugs or gene therapies. The therapeutic compounds are administered systemically, or preferably locally to the targeted site. Local delivery can be accomplished through a needle, cannula, or through a variety of vascular catheters, depending on the location of routes of access. To enhance the systemic or local delivery of the therapeutic compounds, high frequency acoustic waves are generated locally near the target site, and preferably near the site of compound administration. The acoustic waves are produced via laser radiation interaction with an absorbing media and can be produced via thermoelastic expansion, thermodynamic vaporization, material ablation, or plasma formation. Acoustic waves have the effect of temporarily permeabilizing the membranes of local cells, increasing the diffusion of the therapeutic compound into the cells, allowing for decreased total body dosages, decreased side effects, and enabling new therapies.

  6. Recent Perspectives in Ocular Drug Delivery

    PubMed Central

    Gaudana, Ripal; Jwala, J.; Boddu, Sai H. S.; Mitra, Ashim K.

    2015-01-01

    Anatomy and physiology of the eye makes it a highly protected organ. Designing an effective therapy for ocular diseases, especially for the posterior segment, has been considered as a formidable task. Limitations of topical and intravitreal route of administration have challenged scientists to find alternative mode of administration like periocular routes. Transporter targeted drug delivery has generated a great deal of interest in the field because of its potential to overcome many barriers associated with current therapy. Application of nanotechnology has been very promising in the treatment of a gamut of diseases. In this review, we have briefly discussed several ocular drug delivery systems such as microemulsions, nanosuspensions, nanoparticles, liposomes, niosomes, dendrimers, implants, and hydrogels. Potential for ocular gene therapy has also been described in this article. In near future, a great deal of attention will be paid to develop non-invasive sustained drug release for both anterior and posterior segment eye disorders. A better understanding of nature of ocular diseases, barriers and factors affecting in vivo performance, would greatly drive the development of new delivery systems. Current momentum in the invention of new drug delivery systems hold a promise towards much improved therapies for the treatment of vision threatening disorders. PMID:18758924

  7. Drug Delivery for Peripheral Nerve Regeneration

    DTIC Science & Technology

    2015-11-01

    Gale)(months 0-1) b. Optimize nanoporous membrane dimensions ......................(Gale...kinetics of NGF in vitro using our novel drug delivery conduit Material Fabrication The proposed device consists of two concentric tubes, a reservoir...suctioning of material into the conduits, any excess PLGA was allowed to drip out of the molds. The conduits were then placed vertically into a water

  8. Drug delivery strategies for poorly water-soluble drugs.

    PubMed

    Fahr, Alfred; Liu, Xiangli

    2007-07-01

    The drug candidates coming from combinatorial chemistry research and/or the drugs selected from biologically based high-throughput screening are quite often very lipophilic, as these drug candidates exert their pharmacological action at or in biological membranes or membrane-associated proteins. This challenges drug delivery institutions in industry or academia to develop carrier systems for the optimal oral and parenteral administration of these drugs. To mention only a few of the challenges for this class of drugs: their oral bioavailability is poor and highly variable, and carrier development for parenteral administration is faced with problems, including the massive use of surface-active excipients for solubilisation. Formulation specialists are confronted with an even higher level of difficulties when these drugs have to be delivered site specifically. This article addresses the emerging formulation designs for delivering of poorly water-soluble drugs.

  9. Potential new methods for antiepileptic drug delivery.

    PubMed

    Fisher, Robert S; Ho, Jet

    2002-01-01

    Use of novel drug delivery methods could enhance the efficacy and reduce the toxicity of antiepileptic drugs (AEDs). Slow-release oral forms of medication or depot drugs such as skin patches might improve compliance and therefore seizure control. In emergency situations, administration via rectal, nasal or buccal mucosa can deliver the drug more quickly than can oral administration. Slow-release oral forms and rectal forms of AEDs are already approved for use, nasal and buccal administration is currently off-label and skin patches for AEDs are an attractive but currently hypothetical option. Therapies under development may result in the delivery of AEDs directly to the regions of the brain involved in seizures. Experimental protocols are underway to allow continuous infusion of potent excitatory amino acid antagonists into the CSF. In experiments with animal models of epilepsy, AEDs have been delivered successfully to seizure foci in the brain by programmed infusion pumps, acting in response to computerised EEG seizure detection. Inactive prodrugs can be given systemically and activated at the site of the seizure focus by locally released compounds. One such drug under development is DP-VPA (or DP16), which is cleaved to valproic acid (sodium valproate) by phospholipases at the seizure focus. Liposomes and nanoparticles are engineered micro-reservoirs of a drug, with attached antibodies or receptor-specific binding agents designed to target the particles to a specific region of the body. Liposomes in theory could deliver a high concentration of an AED to a seizure focus. Penetration of the blood-brain barrier can be accomplished by linking large particles to iron transferrin or biological toxins that can cross the barrier. In the near future, it is likely that cell transplants that generate neurotransmitters and neuromodulators will accomplish renewable endogenous drug delivery. However, the survival and viability of transplanted cells have yet to be demonstrated

  10. Pharmaceutical applications of mucoadhesion for the non-oral routes.

    PubMed

    Edsman, Katarina; Hägerström, Helene

    2005-01-01

    The adhesion of pharmaceutical formulations to the mucosal tissue offers the possibility of creating an intimate and prolonged contact at the site of administration. This prolonged residence time can result in enhanced absorption and, in combination with a controlled release of the drug, also improved patient compliance by reducing the frequency of administration. During the almost 30 years over which mucoadhesion has been studied, a considerable amount of knowledge has been gained, and much has been learned about the different mechanisms occurring at the formulation-mucus interface and the properties that affect these mechanisms. The in-vivo performance of a dosage form not only depends on the mechanisms occurring at the interface, but also on the properties of the total mucoadhesive complex: the dosage form, the mucosa and the interface between them. A wide variety of methods are used for studying mucoadhesion; some rather similar to the in-vivo situation and some mimicking the interface alone. In this review, the mucus surface, the methods used for the study of mucoadhesion, the different mechanisms involved in mucoadhesion and theories underpinning them have been described. The complexity of mucoadhesion when trying to systemize the subject will also be discussed. The last part of the review describes the buccal, nasal, ocular, vaginal and rectal routes and provides examples of what can be achieved in-vivo when using mucoadhesive formulations.

  11. Advanced materials and nanotechnology for drug delivery.

    PubMed

    Yan, Li; Yang, Yang; Zhang, Wenjun; Chen, Xianfeng

    2014-08-20

    Many biological barriers are of great importance. For example, stratum corneum, the outmost layer of skin, effectively protects people from being invaded by external microorganisms such as bacteria and viruses. Cell membranes help organisms maintain homeostasis by controlling substances to enter and leave cells. However, on the other hand, these biological barriers seriously restrict drug delivery. For instance, stratum corneum has a very dense structure and only allows very small molecules with a molecular weight of below 500 Da to permeate whereas most drug molecules are much larger than that. A wide variety of drugs including genes needs to enter cells for proper functioning but cell membranes are not permeable to them. To overcome these biological barriers, many drug-delivery routes are being actively researched and developed. In this research news, we will focus on two advanced materials and nanotechnology approaches for delivering vaccines through the skin for painless and efficient immunization and transporting drug molecules to cross cell membranes for high-throughput intracellular delivery. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Structural DNA nanotechnology for intelligent drug delivery.

    PubMed

    Chao, Jie; Liu, Huajie; Su, Shao; Wang, Lianhui; Huang, Wei; Fan, Chunhai

    2014-11-01

    Drug delivery carriers have been popularly employed to improve solubility, stability, and efficacy of chemical and biomolecular drugs. Despite the rapid progress in this field, it remains a great challenge to develop an ideal carrier with minimal cytotoxicity, high biocompatibility and intelligence for targeted controlled release. The emergence of DNA nanotechnology offers unprecedented opportunities in this regard. Due to the unparalleled self-recognition properties of DNA molecules, it is possible to create numerous artificial DNA nanostructures with well-defined structures and DNA nanodevices with precisely controlled motions. More importantly, recent studies have proven that DNA nanostructures possess greater permeability to the membrane barrier of cells, which pave the way to developing new drug delivery carriers with nucleic acids, are summarized. In this Concept, recent advances on the design and fabrication of both static and dynamic DNA nanostructures, and the use of these nanostructures for the delivery of various types of drugs, are highlighted. It is also demonstrated that dynamic DNA nanostructures provide the required intelligence to realize logically controlled drug release. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Oral transmucosal drug delivery for pediatric use.

    PubMed

    Lam, Jenny K W; Xu, Yingying; Worsley, Alan; Wong, Ian C K

    2014-06-01

    The formulation of medicines for children remains a challenge. An ideal pediatric formulation must allow accurate dose administration and be in a dosage form that can be handled by the target age group. It is also important to consider the choices and the amount of excipients used in the formulation for this vulnerable age group. Although oral formulations are generally acceptable to most pediatric patients, they are not suitable for drugs with poor oral bioavailability or when a rapid clinical effect is required. In recent years, oral transmucosal delivery has emerged as an attractive route of administration for pediatric patients. With this route of administration, a drug is absorbed through the oral mucosa, therefore bypassing hepatic first pass metabolism and thus avoiding drug degradation or metabolism in the gastrointestinal tract. The high blood flow and relatively high permeability of the oral mucosa allow a quick onset of action to be achieved. It is a simple and non-invasive route of drug administration. However, there are several barriers that need to be overcome in the development of oral transmucosal products. This article aims to provide a comprehensive review of the current development of oral transmucosal delivery specifically for the pediatric population in order to achieve systemic drug delivery. The anatomical and physiological properties of the oral mucosa of infants and young children are carefully examined. The different dosage forms and formulation strategies that are suitable for young patients are discussed.

  14. Chitosan-coupled solid lipid nanoparticles: Tuning nanostructure and mucoadhesion.

    PubMed

    Sandri, Giuseppina; Motta, Simona; Bonferoni, Maria Cristina; Brocca, Paola; Rossi, Silvia; Ferrari, Franca; Rondelli, Valeria; Cantù, Laura; Caramella, Carla; Del Favero, Elena

    2017-01-01

    Solid Lipid Nanoparticles (SLNs) composed of biodegradable physiological lipids have been widely proposed as efficient drug delivery systems, also for ophthalmic administration. Recently, chitosan-associated-SLNs have been developed to further improve the residence time of these colloidal systems in the precorneal area by means of mucoadhesive interaction. In the present study, a one-step preparation protocol was used aiming both at scale-up ease and at stronger coupling between chitosan and SLNs. The resulting particles were chitosan associated-SLNs (CS-SLNs). These nanoparticles were characterized, as compared to both the chitosan-free and the usual chitosan-coated ones, by applying a multi-technique approach: light, neutron and X-ray scattering, Zeta-potential, AFM, calorimetry. It was assessed that, while keeping the features of nano-size and surface-charge required for an efficient vector, these new nanoparticles display a strong and intimate interaction between chitosan and SLNs, far more settled than the usual simple coverage. Moreover, this one-step preparation method allows to obtain a strong and intimate interaction between chitosan and SLNs, firmer than the usual simple coating. This confers to the CS-SLNs an improved mucoadhesion, opening the way for a high-performing ophthalmic formulation.

  15. Chitosan magnetic nanoparticles for drug delivery systems.

    PubMed

    Assa, Farnaz; Jafarizadeh-Malmiri, Hoda; Ajamein, Hossein; Vaghari, Hamideh; Anarjan, Navideh; Ahmadi, Omid; Berenjian, Aydin

    2017-06-01

    The potential of magnetic nanoparticles (MNPs) in drug delivery systems (DDSs) is mainly related to its magnetic core and surface coating. These coatings can eliminate or minimize their aggregation under physiological conditions. Also, they can provide functional groups for bioconjugation to anticancer drugs and/or targeted ligands. Chitosan, as a derivative of chitin, is an attractive natural biopolymer from renewable resources with the presence of reactive amino and hydroxyl functional groups in its structure. Chitosan nanoparticles (NPs), due to their huge surface to volume ratio as compared to the chitosan in its bulk form, have outstanding physico-chemical, antimicrobial and biological properties. These unique properties make chitosan NPs a promising biopolymer for the application of DDSs. In this review, the current state and challenges for the application magnetic chitosan NPs in drug delivery systems were investigated. The present review also revisits the limitations and commercial impediments to provide insight for future works.

  16. Nanocrystals embedded in chitosan-based respirable swellable microparticles as dry powder for sustained pulmonary drug delivery.

    PubMed

    Ni, Rui; Zhao, Jing; Liu, Qiaoyu; Liang, Zhenglin; Muenster, Uwe; Mao, Shirui

    2017-03-01

    In this study, nanocrystals embedded in microparticles were designed to achieve sustained pulmonary drug delivery of hydrophobic drugs. Chitosan based microparticles were engineered to allow sustained drug release via swelling and mucoadhesive properties of the polymer. Taking cinaciguat as a hydrophobic model drug, drug nanocrystals were prepared by high pressure homogenization and then encapsulated in chitosan microparticles via spray drying. Through various in vitro characterizations, it was shown that drug loaded microparticles had a high drug loading with promising aerosolization characteristics (mean volume diameter (Dv50) 3-4μm, experimental mass mean aerodynamic diameter (MMADe) 4-4.5μm, fine particle fraction (FPF%) 40-45%, emitted dose (ED%) 94-95%). The microparticles showed high swelling capacity within 5min, with various sustained drug release rates depending on chitosan concentration and molecular weight. Furthermore, aerosolization performances under various inhalation conditions were investigated. It was found that both inspiratory flow rate and volume had an influence on the aerosolization of developed microparticles, indicating actual inhalation efficiency might be compromised under disease conditions. Taken together, in vitro data indicate that chitosan based swellable microparticles could potentially be useful as nanocrystal carrier to achieve sustained pulmonary delivery. To complete the feasibility assessment of this formulation principle, future in vivo safety and efficacy studies are needed.

  17. Nano-chitosan particles in anticancer drug delivery: An up-to-date review.

    PubMed

    Kamath, Pooja R; Sunil, Dhanya

    2017-02-27

    Cancer is one of the most awful lethal diseases all over the world and the success of its current chemotherapeutic treatment strategies is limited due to several associated drawbacks. The exploration of cancer cell physiology and its microenvironment have exposed the potential of various classes of nanocarriers to deliver anticancer chemotherapeutic agents at the tumor target site. These nanocarriers must evade the immune surveillance system and achieve target selectivity. Besides, they must gain access in to the interior of cancerous cells, evade endosomal entrapment and discharge the drugs in a sustained manner. Chitosan, the second naturally abundant polysaccharide is a biocompatible, biodegradable and mucoadhesive cationic polymer which has been exploited extensively in the last few years in the effective delivery of anticancer chemotherapeutics to the target tumor cells. Therapeutic agent-loaded surface modified chitosan nanoparticles are established to be more stable, permeable and bioactive. This review will provide an up-to-date evidence-based background on recent pharmaceutical advancements in the transformation of chitosan nanoparticles for smart anticancer therapeutic drug delivery.

  18. Drug delivery optimization through Bayesian networks.

    PubMed Central

    Bellazzi, R.

    1992-01-01

    This paper describes how Bayesian Networks can be used in combination with compartmental models to plan Recombinant Human Erythropoietin (r-HuEPO) delivery in the treatment of anemia of chronic uremic patients. Past measurements of hematocrit or hemoglobin concentration in a patient during the therapy can be exploited to adjust the parameters of a compartmental model of the erythropoiesis. This adaptive process allows more accurate patient-specific predictions, and hence a more rational dosage planning. We describe a drug delivery optimization protocol, based on our approach. Some results obtained on real data are presented. PMID:1482938

  19. Multifunctional High Drug Loading Nanocarriers for Cancer Drug Delivery

    NASA Astrophysics Data System (ADS)

    Jin, Erlei

    2011-12-01

    Most anticancer drugs have poor water-solubility, rapid blood clearance, low tumor-selectivity and severe systemic toxicity to healthy tissues. Thus, polymeric nanocarriers have been widely explored for anticancer drugs to solve these problems. However, polymer nanocarriers developed to date still suffer drawbacks including low drug loading contents, premature drug release, slow cellular internalization, slow intracellular drug release and thereby low therapeutic efficiency in cancer thermotherapy. Accordingly, in this dissertation, functional nanocapsules and nanoparticles including high drug loading liposome-like nanocapsules, high drug loading phospholipid-mimic nanocapsules with fast intracellular drug release, high drug loading charge-reversal nanocapsules, TAT based long blood circulation nanoparticles and charge-reversal nuclear targeted nanoparticles are designed and synthesized. These functional carriers have advantages such as high drug loading contents without premature drug release, fast cellular internalization and intracellular drug release, nuclear targeted delivery and long blood circulation. As a result, all these drug carriers show much higher in vitro and in vivo anti-cancer activities.

  20. A new brain drug delivery strategy: focused ultrasound-enhanced intranasal drug delivery.

    PubMed

    Chen, Hong; Chen, Cherry C; Acosta, Camilo; Wu, Shih-Ying; Sun, Tao; Konofagou, Elisa E

    2014-01-01

    Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (BBB), which prevents most drugs from entering into the brain. Intranasal (i.n.) administration is a promising approach for drug delivery to the brain, bypassing the BBB; however, its application has been restricted to particularly potent substances and it does not offer localized delivery to specific brain sites. Focused ultrasound (FUS) in combination with microbubbles can deliver drugs to the brain at targeted locations. The present study proposed to combine these two different platform techniques (FUS+i.n.) for enhancing the delivery efficiency of intranasally administered drugs at a targeted location. After i.n. administration of 40 kDa fluorescently-labeled dextran as the model drug, FUS targeted at one region within the caudate putamen of mouse brains was applied in the presence of systemically administered microbubbles. To compare with the conventional FUS technique, in which intravenous (i.v.) drug injection is employed, FUS was also applied after i.v. injection of the same amount of dextran in another group of mice. Dextran delivery outcomes were evaluated using fluorescence imaging of brain slices. The results showed that FUS+i.n. enhanced drug delivery within the targeted region compared with that achieved by i.n. only. Despite the fact that the i.n. route has limited drug absorption across the nasal mucosa, the delivery efficiency of FUS+i.n. was not significantly different from that of FUS+i.v.. As a new drug delivery platform, the FUS+i.n. technique is potentially useful for treating CNS diseases.

  1. A New Brain Drug Delivery Strategy: Focused Ultrasound-Enhanced Intranasal Drug Delivery

    PubMed Central

    Chen, Hong; Chen, Cherry C.; Acosta, Camilo; Wu, Shih-Ying; Sun, Tao; Konofagou, Elisa E.

    2014-01-01

    Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (BBB), which prevents most drugs from entering into the brain. Intranasal (IN) administration is a promising approach for drug delivery to the brain, bypassing the BBB; however, its application has been restricted to particularly potent substances and it does not offer localized delivery to specific brain sites. Focused ultrasound (FUS) in combination with microbubbles can deliver drugs to the brain at targeted locations. The present study proposed to combine these two different platform techniques (FUS+IN) for enhancing the delivery efficiency of intranasally administered drugs at a targeted location. After IN administration of 40 kDa fluorescently-labeled dextran as the model drug, FUS targeted at one region within the caudate putamen of mouse brains was applied in the presence of systemically administered microbubbles. To compare with the conventional FUS technique, in which intravenous (IV) drug injection is employed, FUS was also applied after IV injection of the same amount of dextran in another group of mice. Dextran delivery outcomes were evaluated using fluorescence imaging of brain slices. The results showed that FUS+IN enhanced drug delivery within the targeted region compared with that achieved by IN only. Despite the fact that the IN route has limited drug absorption across the nasal mucosa, the delivery efficiency of FUS+IN was not significantly different from that of FUS+IV. As a new drug delivery platform, the FUS+IN technique is potentially useful for treating CNS diseases. PMID:25279463

  2. Ultrasound-Mediated Polymeric Micelle Drug Delivery.

    PubMed

    Xia, Hesheng; Zhao, Yue; Tong, Rui

    2016-01-01

    The synthesis of multi-functional nanocarriers and the design of new stimuli-responsive means are equally important for drug delivery. Ultrasound can be used as a remote, non-invasive and controllable trigger for the stimuli-responsive release of nanocarriers. Polymeric micelles are one kind of potential drug nanocarrier. By combining ultrasound and polymeric micelles, a new modality (i.e., ultrasound-mediated polymeric micelle drug delivery) has been developed and has recently received increasing attention. A major challenge remaining in developing ultrasound-responsive polymeric micelles is the improvement of the sensitivity or responsiveness of polymeric micelles to ultrasound. This chapter reviews the recent advance in this field. In order to understand the interaction mechanism between ultrasound stimulus and polymeric micelles, ultrasound effects, such as thermal effect, cavitation effect, ultrasound sonochemistry (including ultrasonic degradation, ultrasound-initiated polymerization, ultrasonic in-situ polymerization and ultrasound site-specific degradation), as well as basic micellar knowledge are introduced. Ultrasound-mediated polymeric micelle drug delivery has been classified into two main streams based on the different interaction mechanism between ultrasound and polymeric micelles; one is based on the ultrasound-induced physical disruption of the micelle and reversible release of payload. The other is based on micellar ultrasound mechanochemical disruption and irreversible release of payload.

  3. ATP-triggered anticancer drug delivery

    NASA Astrophysics Data System (ADS)

    Mo, Ran; Jiang, Tianyue; Disanto, Rocco; Tai, Wanyi; Gu, Zhen

    2014-03-01

    Stimuli-triggered drug delivery systems have been increasingly used to promote physiological specificity and on-demand therapeutic efficacy of anticancer drugs. Here we utilize adenosine-5'-triphosphate (ATP) as a trigger for the controlled release of anticancer drugs. We demonstrate that polymeric nanocarriers functionalized with an ATP-binding aptamer-incorporated DNA motif can selectively release the intercalating doxorubicin via a conformational switch when in an ATP-rich environment. The half-maximal inhibitory concentration of ATP-responsive nanovehicles is 0.24 μM in MDA-MB-231 cells, a 3.6-fold increase in the cytotoxicity compared with that of non-ATP-responsive nanovehicles. Equipped with an outer shell crosslinked by hyaluronic acid, a specific tumour-targeting ligand, the ATP-responsive nanocarriers present an improvement in the chemotherapeutic inhibition of tumour growth using xenograft MDA-MB-231 tumour-bearing mice. This ATP-triggered drug release system provides a more sophisticated drug delivery system, which can differentiate ATP levels to facilitate the selective release of drugs.

  4. Drug Delivery Nanoparticles in Skin Cancers

    PubMed Central

    Dianzani, Chiara; Zara, Gian Paolo; Maina, Giovanni; Pettazzoni, Piergiorgio; Pizzimenti, Stefania; Rossi, Federica; Gigliotti, Casimiro Luca; Ciamporcero, Eric Stefano; Daga, Martina; Barrera, Giuseppina

    2014-01-01

    Nanotechnology involves the engineering of functional systems at nanoscale, thus being attractive for disciplines ranging from materials science to biomedicine. One of the most active research areas of the nanotechnology is nanomedicine, which applies nanotechnology to highly specific medical interventions for prevention, diagnosis, and treatment of diseases, including cancer disease. Over the past two decades, the rapid developments in nanotechnology have allowed the incorporation of multiple therapeutic, sensing, and targeting agents into nanoparticles, for detection, prevention, and treatment of cancer diseases. Nanoparticles offer many advantages as drug carrier systems since they can improve the solubility of poorly water-soluble drugs, modify pharmacokinetics, increase drug half-life by reducing immunogenicity, improve bioavailability, and diminish drug metabolism. They can also enable a tunable release of therapeutic compounds and the simultaneous delivery of two or more drugs for combination therapy. In this review, we discuss the recent advances in the use of different types of nanoparticles for systemic and topical drug delivery in the treatment of skin cancer. In particular, the progress in the treatment with nanocarriers of basal cell carcinoma, squamous cell carcinoma, and melanoma has been reported. PMID:25101298

  5. Limited Efficiency of Drug Delivery to Specific Intracellular Organelles Using Subcellularly "Targeted" Drug Delivery Systems.

    PubMed

    Maity, Amit Ranjan; Stepensky, David

    2016-01-04

    Many drugs have been designed to act on intracellular targets and to affect intracellular processes inside target cells. For the desired effects to be exerted, these drugs should permeate target cells and reach specific intracellular organelles. This subcellular drug targeting approach has been proposed for enhancement of accumulation of these drugs in target organelles and improved efficiency. This approach is based on drug encapsulation in drug delivery systems (DDSs) and/or their decoration with specific targeting moieties that are intended to enhance the drug/DDS accumulation in the intracellular organelle of interest. During recent years, there has been a constant increase in interest in DDSs targeted to specific intracellular organelles, and many different approaches have been proposed for attaining efficient drug delivery to specific organelles of interest. However, it appears that in many studies insufficient efforts have been devoted to quantitative analysis of the major formulation parameters of the DDSs disposition (efficiency of DDS endocytosis and endosomal escape, intracellular trafficking, and efficiency of DDS delivery to the target organelle) and of the resulting pharmacological effects. Thus, in many cases, claims regarding efficient delivery of drug/DDS to a specific organelle and efficient subcellular targeting appear to be exaggerated. On the basis of the available experimental data, it appears that drugs/DDS decoration with specific targeting residues can affect their intracellular fate and result in preferential drug accumulation within an organelle of interest. However, it is not clear whether these approaches will be efficient in in vivo settings and be translated into preclinical and clinical applications. Studies that quantitatively assess the mechanisms, barriers, and efficiencies of subcellular drug delivery and of the associated toxic effects are required to determine the therapeutic potential of subcellular DDS targeting.

  6. Preparation and in vitro characterization of mucoadhesive hydroxypropyl guar microspheres containing amlodipine besylate for nasal administration.

    PubMed

    Swamy, N G N; Abbas, Z

    2011-11-01

    Amlodipine besylate microspheres for intranasal administration were prepared with an aim to avoid first-pass metabolism, to achieve controlled blood level profiles and to improve therapeutic efficacy. Hydroxypropyl Guar, a biodegradable polymer, was used in the preparation of microspheres by employing water in oil emulsification solvent evaporation technique. The formulation variables were drug concentration, emulsifier concentration, temperature, agitation speed and polymer concentration. All the formulations were evaluated for particle size, particle shape and surface morphology by scanning electron microscopy, percentage yield, drug entrapment efficiency, in vitro mucoadhesion test, degree of swelling and in vitro drug diffusion through sheep nasal mucosa. The microspheres obtained were free flowing, spherical and the particles ranged in size from 13.4±2.38 μm to 43.4±1.92 μm very much suitable for nasal delivery. Increasing polymer concentration resulted in increased drug entrapment efficiency and increased particle size. Amlodipine besylate was entrapped into the microspheres with an efficiency of 67.2±1.18 % to 81.8±0.64 %. The prepared microspheres showed good mucoadhesion properties, swellability and sustained the release of the drug over a period of 8 h. The data obtained were analysed by fitment into various kinetic models; it was observed that the drug release was matrix diffusion controlled and the release mechanism was found to be non-Fickian. Stability studies were carried out on selected formulations at 5±3°, 25±2°/60±5% RH and 40±2°/75±5% RH for 90 days. The drug content was observed to be within permissible limits and there were no significant deviations in the in vitro mucoadhesion and in vitro drug diffusion characteristics.

  7. Preparation and In Vitro Characterization of Mucoadhesive Hydroxypropyl Guar Microspheres Containing Amlodipine Besylate for Nasal Administration

    PubMed Central

    Swamy, N. G. N.; Abbas, Z.

    2011-01-01

    Amlodipine besylate microspheres for intranasal administration were prepared with an aim to avoid first-pass metabolism, to achieve controlled blood level profiles and to improve therapeutic efficacy. Hydroxypropyl Guar, a biodegradable polymer, was used in the preparation of microspheres by employing water in oil emulsification solvent evaporation technique. The formulation variables were drug concentration, emulsifier concentration, temperature, agitation speed and polymer concentration. All the formulations were evaluated for particle size, particle shape and surface morphology by scanning electron microscopy, percentage yield, drug entrapment efficiency, in vitro mucoadhesion test, degree of swelling and in vitro drug diffusion through sheep nasal mucosa. The microspheres obtained were free flowing, spherical and the particles ranged in size from 13.4±2.38 μm to 43.4±1.92 μm very much suitable for nasal delivery. Increasing polymer concentration resulted in increased drug entrapment efficiency and increased particle size. Amlodipine besylate was entrapped into the microspheres with an efficiency of 67.2±1.18 % to 81.8±0.64 %. The prepared microspheres showed good mucoadhesion properties, swellability and sustained the release of the drug over a period of 8 h. The data obtained were analysed by fitment into various kinetic models; it was observed that the drug release was matrix diffusion controlled and the release mechanism was found to be non-Fickian. Stability studies were carried out on selected formulations at 5±3°, 25±2°/60±5% RH and 40±2°/75±5% RH for 90 days. The drug content was observed to be within permissible limits and there were no significant deviations in the in vitro mucoadhesion and in vitro drug diffusion characteristics. PMID:23112393

  8. Transdermal drug delivery: from micro to nano

    NASA Astrophysics Data System (ADS)

    Pegoraro, Carla; MacNeil, Sheila; Battaglia, Giuseppe

    2012-03-01

    Delivery across skin offers many advantages compared to oral or intravenous routes of drug administration. Skin however is highly impermeable to most molecules on the basis of size, hydrophilicity, lipophilicity and charge. For this reason it is often necessary to temporarily alter the barrier properties of skin for effective administration. This can be done by applying chemical enhancers, which alter the lipid structure of the top layer of skin (the stratum corneum, SC), by applying external forces such as electric currents and ultrasounds, by bypassing the stratum corneum via minimally invasive microneedles or by using nano-delivery vehicles that can cross and deliver their payload to the deeper layers of skin. Here we present a critical summary of the latest technologies used to increase transdermal delivery.

  9. Biomimetics in drug delivery systems: A critical review.

    PubMed

    Sheikhpour, Mojgan; Barani, Leila; Kasaeian, Alibakhsh

    2017-03-18

    Today, the advanced drug delivery systems have been focused on targeted drug delivery fields. The novel drug delivery is involved with the improvement of the capacity of drug loading in drug carriers, cellular uptake of drug carriers, and the sustained release of drugs within target cells. In this review, six groups of therapeutic drug carriers including biomimetic hydrogels, biomimetic micelles, biomimetic liposomes, biomimetic dendrimers, biomimetic polymeric carriers and biomimetic nanostructures, are studied. The subject takes advantage of the biomimetic methods of productions or the biomimetic techniques for the surface modifications, similar to what accrues in natural cells. Moreover, the effects of these biomimetic approaches for promoting the drug efficiency in targeted drug delivery are visible. The study demonstrates that the fabrication of biomimetic nanocomposite drug carriers could noticeably promote the efficiency of drugs in targeted drug delivery systems.

  10. Intracarotid Delivery of Drugs: The Potential and the Pitfalls

    PubMed Central

    Joshi, Shailendra; Meyers, Phillip M.; Ornstein, Eugene

    2014-01-01

    The major efforts to selectively deliver drugs to the brain in the last decade have relied on smart molecular techniques to penetrate the blood brain barrier while intraarterial drug delivery has drawn relatively little attention. In the last decade there have been rapid advances in endovascular techniques. Modern endovascular procedures can permit highly targeted drug delivery by intracarotid route. Intracarotid drug delivery can be the primary route of drug delivery or it could be used to facilitate the delivery of smart-neuropharmaceuticals. There have been few attempts to systematically understand the kinetics of intracarotid drugs. Anecdotal data suggests that intracarotid drug delivery is effective in the treatment of cerebral vasospasm, thromboembolic strokes, and neoplasms. Neuroanesthesiologists are frequently involved in the care of such high-risk patients. Therefore, it is necessary to understand the applications of intracarotid drug delivery and the unusual kinetics of intracarotid drugs. PMID:18719453

  11. Viruses as nanomaterials for drug delivery.

    PubMed

    Lockney, Dustin; Franzen, Stefan; Lommel, Steven

    2011-01-01

    Virus delivery vectors are one among the many nanomaterials that are being developed as drug delivery materials. This chapter focuses on methods utilizing plant virus nanoparticles (PVNs) synthesized from the Red clover necrotic mosaic virus (RCNMV). A successful vector must be able to effectively carry and subsequently deliver a drug cargo to a specific target. In the case of the PVNs, we describe two types of ways cargo can be loaded within these structures: encapsidation and infusion. Several targeting approaches have been used for PVNs based on bioconjugate chemistry. Herein, examples of such approaches will be given that have been used for RCNMV as well as for other PVNs in the literature. Further, we describe characterization of PVNs, in vitro cell studies that can be used to test the efficacy of a targeting vector, and potential routes for animal administration.

  12. Nanotechnology Approaches for Ocular Drug Delivery

    PubMed Central

    Xu, Qingguo; Kambhampati, Siva P.; Kannan, Rangaramanujam M.

    2013-01-01

    Blindness is a major health concern worldwide that has a powerful impact on afflicted individuals and their families, and is associated with enormous socio-economical consequences. The Middle East is heavily impacted by blindness, and the problem there is augmented by an increasing incidence of diabetes in the population. An appropriate drug/gene delivery system that can sustain and deliver therapeutics to the target tissues and cells is a key need for ocular therapies. The application of nanotechnology in medicine is undergoing rapid progress, and the recent developments in nanomedicine-based therapeutic approaches may bring significant benefits to address the leading causes of blindness associated with cataract, glaucoma, diabetic retinopathy and retinal degeneration. In this brief review, we highlight some promising nanomedicine-based therapeutic approaches for drug and gene delivery to the anterior and posterior segments. PMID:23580849

  13. Diatomite silica nanoparticles for drug delivery

    NASA Astrophysics Data System (ADS)

    Ruggiero, Immacolata; Terracciano, Monica; Martucci, Nicola M.; De Stefano, Luca; Migliaccio, Nunzia; Tatè, Rosarita; Rendina, Ivo; Arcari, Paolo; Lamberti, Annalisa; Rea, Ilaria

    2014-07-01

    Diatomite is a natural fossil material of sedimentary origin, constituted by fragments of diatom siliceous skeletons. In this preliminary work, the properties of diatomite nanoparticles as potential system for the delivery of drugs in cancer cells were exploited. A purification procedure, based on thermal treatments in strong acid solutions, was used to remove inorganic and organic impurities from diatomite and to make them a safe material for medical applications. The micrometric diatomite powder was reduced in nanoparticles by mechanical crushing, sonication, and filtering. Morphological analysis performed by dynamic light scattering and transmission electron microscopy reveals a particles size included between 100 and 300 nm. Diatomite nanoparticles were functionalized by 3-aminopropyltriethoxysilane and labeled by tetramethylrhodamine isothiocyanate. Different concentrations of chemically modified nanoparticles were incubated with cancer cells and confocal microscopy was performed. Imaging analysis showed an efficient cellular uptake and homogeneous distribution of nanoparticles in cytoplasm and nucleus, thus suggesting their potentiality as nanocarriers for drug delivery.

  14. Inhalation drug delivery devices: technology update

    PubMed Central

    Ibrahim, Mariam; Verma, Rahul; Garcia-Contreras, Lucila

    2015-01-01

    The pulmonary route of administration has proven to be effective in local and systemic delivery of miscellaneous drugs and biopharmaceuticals to treat pulmonary and non-pulmonary diseases. A successful pulmonary administration requires a harmonic interaction between the drug formulation, the inhaler device, and the patient. However, the biggest single problem that accounts for the lack of desired effect or adverse outcomes is the incorrect use of the device due to lack of training in how to use the device or how to coordinate actuation and aerosol inhalation. This review summarizes the structural and mechanical features of aerosol delivery devices with respect to mechanisms of aerosol generation, their use with different formulations, and their advantages and limitations. A technological update of the current state-of-the-art designs proposed to overcome current challenges of existing devices is also provided. PMID:25709510

  15. The effects of the thiolation with thioglycolic acid and l-cysteine on the mucoadhesion properties of the starch-graft-poly(acrylic acid).

    PubMed

    Gök, M Koray; Demir, Kamber; Cevher, Erdal; Özsoy, Yıldız; Cirit, Ümüt; Bacınoğlu, Süleyman; Özgümüş, Saadet; Pabuccuoğlu, Serhat

    2017-05-01

    The aim of this study is to investigate the effects of the thiolation on the mucoadhesion characteristics of the gelatinized and crosslinked wheat starch-graft-poly(acrylic acid) [(WS-g-PAA)gc] for potential use in drug delivery via vaginal route. Thiolation of (WS-g-PAA)gc was first time realized using l-cysteine hydrochloride monohydrate (CyS) and thioglycolic acid (TGA). These conjugates [(WS-g-PAA)gcth] were characterized using FTIR. The free SH group, mucoadhesion, cytotoxicity characteristics and the mechanism of the thiolation were also evaluated. To obtain fundamental data for possible application such as drug carrier, in vitro and in vivo progesterone release profiles from the mucoadhesive tablet formulations were also determined. The results showed that, vaginal tablet containing (WS-g-PAA)gc-TGA, which has not contain free SH groups in its structure, displays higher mucoadhesion than (WS-g-PAA)gc and (WS-g-PAA)gc-CyS. This tablet formulation can also be used as a drug carrier in vaginal applications.

  16. Microneedle Coating Techniques for Transdermal Drug Delivery

    PubMed Central

    Haj-Ahmad, Rita; Khan, Hashim; Arshad, Muhammad Sohail; Rasekh, Manoochehr; Hussain, Amjad; Walsh, Susannah; Li, Xiang; Chang, Ming-Wei; Ahmad, Zeeshan

    2015-01-01

    Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN) based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips) are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA) based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described) have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates. PMID:26556364

  17. Nanogel Carrier Design for Targeted Drug Delivery

    PubMed Central

    Eckmann, D. M.; Composto, R. J.; Tsourkas, A.; Muzykantov, V. R.

    2014-01-01

    Polymer-based nanogel formulations offer features attractive for drug delivery, including ease of synthesis, controllable swelling and viscoelasticity as well as drug loading and release characteristics, passive and active targeting, and the ability to formulate nanogel carriers that can respond to biological stimuli. These unique features and low toxicity make the nanogels a favorable option for vascular drug targeting. In this review, we address key chemical and biological aspects of nanogel drug carrier design. In particular, we highlight published studies of nanogel design, descriptions of nanogel functional characteristics and their behavior in biological models. These studies form a compendium of information that supports the scientific and clinical rationale for development of this carrier for targeted therapeutic interventions. PMID:25485112

  18. Microneedle Coating Techniques for Transdermal Drug Delivery.

    PubMed

    Haj-Ahmad, Rita; Khan, Hashim; Arshad, Muhammad Sohail; Rasekh, Manoochehr; Hussain, Amjad; Walsh, Susannah; Li, Xiang; Chang, Ming-Wei; Ahmad, Zeeshan

    2015-11-05

    Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN) based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips) are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA) based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described) have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates.

  19. Injected nanocrystals for targeted drug delivery

    PubMed Central

    Lu, Yi; Li, Ye; Wu, Wei

    2016-01-01

    Nanocrystals are pure drug crystals with sizes in the nanometer range. Due to the advantages of high drug loading, platform stability, and ease of scaling-up, nanocrystals have been widely used to deliver poorly water-soluble drugs. Nanocrystals in the blood stream can be recognized and sequestered as exogenous materials by mononuclear phagocytic system (MPS) cells, leading to passive accumulation in MPS-rich organs, such as liver, spleen and lung. Particle size, morphology and surface modification affect the biodistribution of nanocrystals. Ligand conjugation and stimuli-responsive polymers can also be used to target nanocrystals to specific pathogenic sites. In this review, the progress on injected nanocrystals for targeted drug delivery is discussed following a brief introduction to nanocrystal preparation methods, i.e., top-down and bottom-up technologies. PMID:27006893

  20. Targeted Delivery of Protein Drugs by Nanocarriers

    PubMed Central

    Solaro, Roberto; Chiellini, Federica; Battisti, Antonella

    2010-01-01

    Recent advances in biotechnology demonstrate that peptides and proteins are the basis of a new generation of drugs. However, the transportation of protein drugs in the body is limited by their high molecular weight, which prevents the crossing of tissue barriers, and by their short lifetime due to immuno response and enzymatic degradation. Moreover, the ability to selectively deliver drugs to target organs, tissues or cells is a major challenge in the treatment of several human diseases, including cancer. Indeed, targeted delivery can be much more efficient than systemic application, while improving bioavailability and limiting undesirable side effects. This review describes how the use of targeted nanocarriers such as nanoparticles and liposomes can improve the pharmacokinetic properties of protein drugs, thus increasing their safety and maximizing the therapeutic effect.

  1. Controlled Ocular Drug Delivery with Nanomicelles

    PubMed Central

    Vaishya, Ravi D.; Khurana, Varun; Patel, Sulabh; Mitra, Ashim K.

    2014-01-01

    Many vision threatening ocular diseases such as age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, and proliferative vitreoretinopathy may result in blindness. Ocular drug delivery specifically to the intraocular tissues remains a challenging task due to the presence of various physiological barriers. Nonetheless, recent advancements in the field of nanomicelle based novel drug delivery system could fulfil these unmet needs. Nanomicelles consists of amphiphilic molecules that self-assemble in aqueous media to form organized supramolecular structures. Micelles can be prepared in various sizes (10 to 1000nm) and shapes depending on the molecular weights of the core and corona forming blocks. Nanomicelles have been an attractive carriers for their potential to solubilize hydrophobic molecules in aqueous solution. In addition, small size in nanometer range and highly modifiable surface properties have been reported to be advantageous in ocular drug delivery. In the present review various factors influencing rationale design of nanomicelles formulation and disposition are discussed along with case studies. Despite the progress in the field, influence of various properties of nanomicelles such as size, shape, surface charge, rigidity of structure on ocular disposition need to be studied in further details to develop an efficient nanocarrier system. PMID:24888969

  2. Iontophoretic drug delivery across the nail.

    PubMed

    Delgado-Charro, Maria Begoña

    2012-01-01

    Topical drug delivery to treat nail diseases such as onychomycosis and psoriasis is receiving increasing attention. Topical nail delivery is challenged by the complicated structure of the nail and the low permeability of most drugs across the nail plate. Considerable effort has been directed at developing methods to promote drug permeation across the nail plate. Iontophoresis efficiently enhances molecular transport across the skin and the eye and is now being tested for its potential in ungual delivery. This review covers the basic mechanisms of transport (electro-osmosis and -migration) and their relative contribution to nail iontophoresis as well as the key factors governing nail permselectivity and ionic transport numbers. Methodological issues concerning research in this area are summarized. The data available in vivo on nail iontophoresis of terbinafine specifically are reviewed in separate sections. Our understanding of nail iontophoresis has improved considerably since 2007; most decisively, the feasibility of nail iontophoresis in vivo has been clearly demonstrated. Future work is required to establish the adequate implementation of the technique so that its clinical efficacy to treat onychomycosis and nail psoriasis can be unequivocally determined.

  3. Ultrasound-mediated nail drug delivery system.

    PubMed

    Abadi, Danielle; Zderic, Vesna

    2011-12-01

    A novel ultrasound-mediated drug delivery system has been developed for treatment of a nail fungal disorder (onychomycosis) by improving delivery to the nail bed using ultrasound to increase the permeability of the nail. The slip-in device consists of ultrasound transducers and drug delivery compartments above each toenail. The device is connected to a computer, where a software interface allows users to select their preferred course of treatment. In in vitro testing, canine nails were exposed to 3 energy levels (acoustic power of 1.2 W and exposure durations of 30, 60, and 120 seconds). A stereo -microscope was used to determine how much of a drug-mimicking compound was delivered through the nail layers by measuring brightness on the cross section of each nail tested at each condition, where brightness level decreases coincide with increases in permeability. Each of the 3 energy levels tested showed statistical significance when compared to the control (P < .05) with a permeability factor of 1.3 after 30 seconds of exposure, 1.3 after 60 seconds, and 1.5 after 120 seconds, where a permeability factor of 1 shows no increase in permeability. Current treatments for onychomycosis include systemic, topical, and surgical. Even when used all together, these treatments typically take a long time to result in nail healing, thus making this ultrasound-mediated device a promising alternative.

  4. A model of axonal transport drug delivery

    NASA Astrophysics Data System (ADS)

    Kuznetsov, Andrey V.

    2012-04-01

    In this paper a model of targeted drug delivery by means of active (motor-driven) axonal transport is developed. The model is motivated by recent experimental research by Filler et al. (A.G. Filler, G.T. Whiteside, M. Bacon, M. Frederickson, F.A. Howe, M.D. Rabinowitz, A.J. Sokoloff, T.W. Deacon, C. Abell, R. Munglani, J.R. Griffiths, B.A. Bell, A.M.L. Lever, Tri-partite complex for axonal transport drug delivery achieves pharmacological effect, Bmc Neuroscience 11 (2010) 8) that reported synthesis and pharmacological efficiency tests of a tri-partite complex designed for axonal transport drug delivery. The developed model accounts for two populations of pharmaceutical agent complexes (PACs): PACs that are transported retrogradely by dynein motors and PACs that are accumulated in the axon at the Nodes of Ranvier. The transitions between these two populations of PACs are described by first-order reactions. An analytical solution of the coupled system of transient equations describing conservations of these two populations of PACs is obtained by using Laplace transform. Numerical results for various combinations of parameter values are presented and their physical significance is discussed.

  5. Synthesis, characterization of thiolated karaya gum and evaluation of effect of pH on its mucoadhesive and sustained release properties.

    PubMed

    Bahulkar, Swati S; Munot, Neha M; Surwase, Sachin S

    2015-10-05

    Present study aims at synthesis and characterization of thiolated gum karaya by reacting karaya gum with 80% thioglycolic acid resulting in esterification and immobilization of thiol groups on polymeric backbone. Immobilized thiol groups were found to be 5.026 mM/g determined by Ellman's method. It was characterized by FTIR, DSC and XRD. Directly compressible tablets prepared using thiolated gum displayed more disintegration time, swelling and mucoadhesion with increase in pH of medium simulating gastric and intestinal environment than plain gum. Controlled drug release for more than 24h by Fickian diffusion following Korsemeyer-Peppas model was observed with Metoprolol Succinate as a model drug as compared to plain gum which released more than 90% of the drug within 2h. Synthesized thiomer showed no cytotoxicity determined using HepG2 cell line. According to these results, thiolated gum karaya seems to be promising excipient for the development of mucoadhesive drug delivery systems.

  6. An in vitro study of mucoadhesion and biocompatibility of polymer coated liposomes on HT29-MTX mucus-producing cells.

    PubMed

    Adamczak, Małgorzata I; Hagesaether, Ellen; Smistad, Gro; Hiorth, Marianne

    2016-02-10

    Drug delivery to the oral cavity poses a significant challenge due to the short residence time of the formulations at the site of action. From this point of view, nanoparticulate drug delivery systems with ability to adhere to the oral mucosa are advantageous as they could increase the effectiveness of the therapy. Positively, negatively and neutrally charged liposomes were coated with four different types of polymers: alginate, low-ester pectin, chitosan and hydrophobically modified ethyl hydroxyethyl cellulose. The mucoadhesion was studied using a novel in vitro method allowing the liposomes to interact with a mucus-producing confluent HT29-MTX cell-line without applying any external force. MTT viability and paracellular permeability tests were conducted on the same cell-line. The alginate-coated liposomes achieved a high specific (genuine) mucin interaction, with a low potential of cell-irritation. The positively charged uncoated liposomes achieved the highest initial mucoadhesion, but also displayed a higher probability of cell-irritation. The chitosan-coated liposomes displayed the highest potential for long lasting mucoadhesion, but with the drawback of a higher general adhesion (tack) and a higher potential for irritating the cells.

  7. Surface modification of PLGA nanoparticles by carbopol to enhance mucoadhesion and cell internalization.

    PubMed

    Surassmo, Suvimol; Saengkrit, Nattika; Ruktanonchai, Uracha Rungsardthong; Suktham, Kunat; Woramongkolchai, Noppawan; Wutikhun, Tuksadon; Puttipipatkhachorn, Satit

    2015-06-01

    Mucoadhesive poly (lactic-co-glycolic acid) (PLGA) nanoparticles having a modified shell-matrix derived from polyvinyl alcohol (PVA) and Carbopol (CP), a biodegradable polymer coating, to improve the adhesion and cell transfection properties were developed. The optimum formulations utilized a CP concentration in the range of 0.05-0.2%w/v, and were formed using modified emulsion-solvent evaporation technique. The resulting CP-PLGA nanoparticles were characterized in terms of their physical and chemical properties. The absorbed CP on the PLGA shell-matrix was found to affect the particle size and surface charge, with 0.05% CP giving rise to smooth spherical particles (0.05CP-PLGA) with the smallest size (285.90 nm), and strong negative surface charge (-25.70 mV). The introduction of CP results in an enhancement of the mucoadhesion between CP-PLGA nanoparticles and mucin particles. In vitro cell internalization studies highlighted the potential of 0.05CP-PLGA nanoparticles for transfection into SiHa cells, with uptake being time dependent. Additionally, cytotoxicity studies of CP-PLGA nanoparticles against SiHa cancer cells indicated that low concentrations of the nanoparticles were non-toxic to cells (cell viability >80%). From the various formulations studied, 0.05CP-PLGA nanoparticles proved to be the optimum model carrier having the required mucoadhesive profile and could be an alternative therapeutic efficacy carrier for targeted mucosal drug delivery systems with biodegradable polymer.

  8. Immobilization of coacervate microcapsules in multilayer sodium alginate beads for efficient oral anticancer drug delivery.

    PubMed

    Feng, Chao; Song, Ruixi; Sun, Guohui; Kong, Ming; Bao, Zixian; Li, Yang; Cheng, Xiaojie; Cha, Dongsu; Park, Hyunjin; Chen, Xiguang

    2014-03-10

    We have designed and evaluated coacervate microcapsules-immobilized multilayer sodium alginate beads (CMs-M-ALG-Beads) for oral drug delivery. The CMs-M-ALG-Beads were prepared by immobilization of doxorubicin hydrochloride (DOX) loaded chitosan/carboxymethyl coacervate microcapsules (DOX:CS/CMCS-CMs) in the core and layers of the multilayer sodium alginate beads. The obtained CMs-M-ALG-beads exhibited layer-by-layer structure and rough surface with many nanoscale particles. The swelling characteristic and drug release results indicated that 4-layer CMs-M-ALG-Beads possessed favorable gastric acid tolerance (the swelling rate <5%, the cumulative drug release rate <3.8%). In small intestine, the intact DOX:CS/CMCS-CMs were able to rapidly release from CMs-M-ALG-Beads with the dissolution of ALG matrix. Ex vivo intestinal mucoadhesive and permeation showed that CMs-M-ALG-Beads exhibited continued growth for P(app) values of DOX, which was 1.07-1.15 folds and 1.28-1.38 folds higher than DOX:CS:CMCS-CMs in rat jejunum and ileum, respectively, demonstrating that CMs-M-ALG-Beads were able to enhance the absorption of DOX by controlled releasing DOX:CS/CMCS-CMs and prolonging the contact time between the DOX:CS/CMCS-CMs and small intestinal mucosa.

  9. Drug Delivery to CNS: Challenges and Opportunities with Emphasis on Biomaterials Based Drug Delivery Strategies.

    PubMed

    Khambhla, Ekta; Shah, Viral; Baviskar, Kalpesh

    2016-01-01

    The current epoch has witnessed a lifestyle impregnated with stress, which is a major cause of several neurological disorders. High morbidity and mortality rate due to neurological diseases and disorders have generated a huge social impact. Despite voluminous research, patients suffering from fatal and/or debilitating CNS diseases such as brain tumors, HIV, encephalopathy, Alzheimer's, epilepsy, Parkinson's, migraine and multiple sclerosis outnumbered those suffering from systemic cancer or heart diseases. The brain being a highly sensitive neuronal organ, has evolved with vasculature barriers, which regulates the efflux and influx of substances to CNS. Treatment of CNS diseases/disorders is challenging because of physiologic, metabolic and biochemical obstacles created by these barriers which comprise mainly of BBB and BCFB. The inability of achieving therapeutically active concentration has become the bottleneck level difficulty, hampering the therapeutic efficiency of several promising drug candidates for CNS related disorders. Parallel maturation of an effective CNS drug delivery strategy with CNS drug discovery is the need of the hour. Recently, the focus of the pharmaceutical community has aggravated in the direction of developing novel and more efficient drug delivery systems, giving the potential of more effective and safer CNS therapies. The present review outlines several hurdles in drug delivery to the CNS along with ideal physicochemical properties desired in drug substance/formulation for CNS delivery. The review also focuses on different conventional and novel strategies for drug delivery to the CNS. The article also assesses and emphasizes on possible benefits of biomaterial based formulations for drug delivery to the CNS.

  10. Nose to brain microemulsion-based drug delivery system of rivastigmine: formulation and ex-vivo characterization.

    PubMed

    Shah, Brijesh M; Misra, Manju; Shishoo, Chamanlal J; Padh, Harish

    2015-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to irreversible loss of neurons, cognition and formation of abnormal protein aggregates. Rivastigmine, a reversible cholinesterase inhibitor used for the treatment of AD, undergoes extensive first-pass metabolism, thus limiting its absolute bioavailability to only 36% after 3-mg dose. Due to extreme aqueous solubility, rivastigmine shows poor penetration and lesser concentration in the brain thus requiring frequent oral dosing. This investigation was aimed to formulate microemulsion (ME) and mucoadhesive microemulsions (MMEs) of rivastigmine for nose to brain delivery and to compare percentage drug diffused for both systems using in-vitro and ex-vivo study. Rivastigmine-loaded ME and MMEs were prepared by titration method and characterized for drug content, globule size distribution, zeta potential, pH, viscosity and nasal ciliotoxicity study. Rivastigmine-loaded ME system containing 8% w/w Capmul MCM EP, 44% w/w Labrasol:Transcutol-P (1:1) and 48% w/w distilled water was formulated, whereas 0.3% w/w chitosan (CH) and cetyl trimethyl ammonium bromide (as mucoadhesive agents) were used to formulate MMEs, respectively. ME and MMEs formulations were transparent with drug content, globule size and zeta potential in the range of 98.59% to 99.43%, 53.8 nm to 55.4 nm and -2.73 mV to 6.52 mV, respectively. MME containing 0.3% w/w CH followed Higuchi model (r(2) = 0.9773) and showed highest diffusion coefficient. It was free from nasal ciliotoxicity and stable for three months. However, the potential of developed CH-based MME for nose to brain delivery of rivastigmine can only be established after in-vivo and biodistribution study.

  11. Drug Delivery to the Ischemic Brain

    PubMed Central

    Thompson, Brandon J.; Ronaldson, Patrick T.

    2014-01-01

    Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events inneurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for acute ischemic stroke treatment, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can “rescue” salvageable brain tissue and/or protect BBB integrity during ischemic stroke. One class of drugs that may enable neural cell rescue following cerebral ischemia/reperfusion injury is the HMG-CoA reductase inhibitors (i.e., statins). Understanding potential CNS drug delivery pathways for statins is critical to their utility in ischemic stroke. Here, we review molecular pathways associated with cerebral ischemia and novel approaches for delivering drugs to treat ischemic disease. Specifically, we discuss utility of endogenous BBB drug uptake transporters such as organic anion transporting polypeptides (OATPs/Oatps) and nanotechnology-based carriers for optimization of CNS drug delivery. Overall, this chapter highlights state-of-the-art technologies that may improve pharmacotherapy of cerebral ischemia. PMID:25307217

  12. Microemulsions based transdermal drug delivery systems.

    PubMed

    Vadlamudi, Harini C; Narendran, Hyndavi; Nagaswaram, Tejeswari; Yaga, Gowri; Thanniru, Jyotsna; Yalavarthi, Prasanna R

    2014-01-01

    Since the discovery of microemulsions by Jack H Schulman, there has been huge progress made in applying microemulsion systems in plethora of research and industrial process. Microemulsions are optically isotropic systems consisting of water, oil and amphiphile. These systems are beneficial due to their thermodynamic stability, optical clarity, ease of preparation, higher diffusion and absorption rates. Moreover, it has been reported that the ingredients of microemulsion can effectively overcome the diffusion barrier and penetrate through the stratum corneum of the skin. Hence it becomes promising for both transdermal and dermal drug delivery. However, low viscosity of microemulsion restrains its applicability in pharmaceutical industry. To overcome the above drawback, the low viscous microemulsions were added to viscous gel bases to potentiate its applications as topical drug delivery systems so that various drug related toxic effects and erratic drug absorption can be avoided. The present review deals with the microemulsions, various techniques involved in the development of organic nanoparticles. The review emphasized on microemulsion based systems such as hydrogels and organogels. The physicochemical characteristics, mechanical properties, rheological and stability principles involved in microemulsion based viscous gels were also explored.

  13. Phospholipid nanodisc engineering for drug delivery systems.

    PubMed

    Murakami, Tatsuya

    2012-06-01

    Biocompatible mesoscale nanoparticles (5-100 nm in diameter) are attractive tools for drug delivery. Among them are several types of liposomes and polymer micelles already in clinical trial or use. Generally, biocompatibility of such particles is achieved by coating them with polyethylene glycol (PEG). Without PEG coating, particles are quickly trapped in the reticuloendothelial system when intravenously administered. However, recent studies have revealed several potential problems with PEG coating, including antigenicity and restriction of cellular uptake. This has motivated the development of alternative drug and gene delivery vehicles, including chemically and genetically engineered high-density lipoprotein (HDL)-like nanodiscs or "bicelles". HDL is a naturally occurring mesoscale nanoparticle that normally ferries cholesterol around in the body. Its initial "nascent" form is thought to be a simple 10 nm disc of phospholipids in a bilayer, and can be easily synthesized in vitro by mixing recombinant apoA-I proteins with various phospholipids. In this review, the use of synthetic HDL-like phospholipid nanodiscs as biocompatible drug carriers is summarized, focussing on manufacturing, size-control, drug loading and cell targeting. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Silk Electrogel Based Gastroretentive Drug Delivery System

    NASA Astrophysics Data System (ADS)

    Wang, Qianrui

    Gastric cancer has become a global pandemic and there is imperative to develop efficient therapies. Oral dosing strategy is the preferred route to deliver drugs for treating the disease. Recent studies suggested silk electro hydrogel, which is pH sensitive and reversible, has potential as a vehicle to deliver the drug in the stomach environment. The aim of this study is to establish in vitro electrogelation e-gel based silk gel as a gastroretentive drug delivery system. We successfully extended the duration of silk e-gel in artificial gastric juice by mixing silk solution with glycerol at different ratios before the electrogelation. Structural analysis indicated the extended duration was due to the change of beta sheet content. The glycerol mixed silk e-gel had good doxorubicin loading capability and could release doxorubicin in a sustained-release profile. Doxorubicin loaded silk e-gels were applied to human gastric cancer cells. Significant cell viability decrease was observed. We believe that with further characterization as well as functional analysis, the silk e-gel system has the potential to become an effective vehicle for gastric drug delivery applications.

  15. Radionuclide imaging of liposomal drug delivery.

    PubMed

    van der Geest, Tessa; Laverman, Peter; Metselaar, Josbert M; Storm, Gert; Boerman, Otto C

    2016-09-01

    Ever since their discovery, liposomes have been radiolabeled to monitor their fate in vivo. Despite extensive preclinical studies, only a limited number of radiolabeled liposomal formulations have been examined in patients. Since they can play a crucial role in patient management, it is of importance to enable translation of radiolabeled liposomes into the clinic. Liposomes have demonstrated substantial advantages as drug delivery systems and can be efficiently radiolabeled. Potentially, radiolabeled drug-loaded liposomes form an elegant theranostic system, which can be tracked in vivo using single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. In this review, we discuss important aspects of liposomal research with a focus on the use of radiolabeled liposomes and their potential role in drug delivery and monitoring therapeutic effects. Radiolabeled drug-loaded liposomes have been poorly investigated in patients and no radiolabeled liposomes have been approved for use in clinical practice. Evaluation of the risks, pharmacokinetics, pharmacodynamics and toxicity is necessary to meet pharmaceutical and commercial requirements. It remains to be demonstrated whether the results found in animal studies translate to humans before radiolabeled liposomes can be implemented into clinical practice.

  16. Multifunctional Delivery Systems for Advanced oral Uptake of Peptide/Protein Drugs.

    PubMed

    Park, Jin Woo; Kim, Sun Jin; Kwag, Dong Sup; Kim, Sol; Park, Jeyoung; Youn, Yu Seok; Bae, You Han; Lee, Eun Seong

    2015-01-01

    In recent years, advances in biotechnology and protein engineering have enabled the production of large quantities of proteins and peptides as important therapeutic agents. Various researchers have used biocompatible functional polymers to prepare oral dosage forms of proteins and peptides for chronic use and for easier administration to enhance patient compliance. However, there is a need to enhance their safety and effectiveness further. Most macromolecules undergo severe denaturation at low pH and enzymatic degradation in the gastrointestinal tract. The macromolecules' large molecular size and low lipophilicity cause low permeation through the intestinal membrane. The major strategies that have been used to overcome these challenges (in oral drug carrier systems) can be classified as follows: enteric coating or encapsulation with pH-sensitive polymers or mucoadhesive polymers, co-administration of protease inhibitors, incorporation of absorption enhancers, modification of the physicochemical properties of the macromolecules, and site-specific delivery to the colon. This review attempts to summarize the various advanced oral delivery carriers, including nanoparticles, lipid carriers, such as liposomes, nano-aggregates using amphiphilic polymers, complex coacervation of oppositely charged polyelectrolytes, and inorganic porous particles. The particles were formulated and/or surface modified with functional polysaccharides or synthetic polymers to improve oral bioavailability of proteins and peptides. We also discuss formulation strategies to overcome barriers, therapeutic efficacies in vivo, and potential benefits and issues for successful oral dosage forms of the proteins and peptides.

  17. Protein-Based Nanomedicine Platforms for Drug Delivery

    SciTech Connect

    Ma Ham, Aihui; Tang, Zhiwen; Wu, Hong; Wang, Jun; Lin, Yuehe

    2009-08-03

    Drug delivery systems have been developed for many years, however some limitations still hurdle the pace of going to clinical phase, for example, poor biodistribution, drug molecule cytotoxicity, tissue damage, quick clearance from the circulation system, solubility and stability of drug molecules. To overcome the limitations of drug delivery, biomaterials have to be developed and applied to drug delivery to protect the drug molecules and to enhance the drug’s efficacy. Protein-based nanomedicine platforms for drug delivery are platforms comprised of naturally self-assembled protein subunits of the same protein or a combination of proteins making up a complete system. They are ideal for drug delivery platforms due to their biocompatibility and biodegradability coupled with low toxicity. A variety of proteins have been used and characterized for drug delivery systems including the ferritin/apoferritin protein cage, plant derived viral capsids, the small Heat shock protein (sHsp) cage, albumin, soy and whey protein, collagen, and gelatin. There are many different types and shapes that have been prepared to deliver drug molecules using protein-based platforms including the various protein cages, microspheres, nanoparticles, hydrogels, films, minirods and minipellets. There are over 30 therapeutic compounds that have been investigated with protein-based drug delivery platforms for the potential treatment of various cancers, infectious diseases, chronic diseases, autoimmune diseases. In protein-based drug delivery platforms, protein cage is the most newly developed biomaterials for drug delivery and therapeutic applications. Their uniform sizes, multifunctions, and biodegradability push them to the frontier for drug delivery. In this review, the recent strategic development of drug delivery has been discussed with a special emphasis upon the polymer based, especially protein-based nanomedicine platforms for drug delivery. The advantages and disadvantages are also

  18. Synthesis of Thiolated Alginate and Evaluation of Mucoadhesiveness, Cytotoxicity and Release Retardant Properties

    PubMed Central

    Jindal, A. B.; Wasnik, M. N.; Nair, Hema A.

    2010-01-01

    Modification of polymers by covalent attachment of thiol bearing pendant groups is reported to impart many beneficial properties to them. Hence in the present study, sodium alginate–cysteine conjugate was synthesized by carbodiimide mediated coupling under varying reaction conditions and the derivatives characterized for thiol content. The thiolated alginate species synthesized had bound thiol content ranging from 247.8±11.03–324.54±10.107 ΅mol/g of polymer depending on the reaction conditions. Matrix tablets based on sodium alginate-cysteine conjugate and native sodium alginate containing tramadol hydrochloride as a model drug were prepared and mucoadhesive strength and in vitro drug release from the tablets were compared. Tablets containing 75 mg sodium alginate-cysteine conjugate could sustain release of 10 mg of model drug for 3 h, whereas 90% of the drug was released within 1 h from corresponding tablets prepared using native sodium alginate. An approximately 2-fold increase in the minimal detachment force of the tablets from an artificial mucin film was observed for sodium alginate–cysteine conjugate as compared to native sodium alginate. In vitro cytotoxicity studies in L-929 mouse fibroblast cells studied using an MTT assay revealed that at low concentrations of polymer, sodium alginate–cysteine conjugate was less toxic to L-929 mouse fibroblast cell line when compared to native sodium alginate. Hence, thiolation is found to be a simple route to improving polymer performance. The combination of improved controlled drug release and mucoadhesive properties coupled with the low toxicity of these new excipients builds up immense scope for the use of thiolated polymers in mucoadhesive drug delivery systems. PMID:21969750

  19. Recent advances in chitosan-based nanoparticulate pulmonary drug delivery

    NASA Astrophysics Data System (ADS)

    Islam, Nazrul; Ferro, Vito

    2016-07-01

    The advent of biodegradable polymer-encapsulated drug nanoparticles has made the pulmonary route of administration an exciting area of drug delivery research. Chitosan, a natural biodegradable and biocompatible polysaccharide has received enormous attention as a carrier for drug delivery. Recently, nanoparticles of chitosan (CS) and its synthetic derivatives have been investigated for the encapsulation and delivery of many drugs with improved targeting and controlled release. Herein, recent advances in the preparation and use of micro-/nanoparticles of chitosan and its derivatives for pulmonary delivery of various therapeutic agents (drugs, genes, vaccines) are reviewed. Although chitosan has wide applications in terms of formulations and routes of drug delivery, this review is focused on pulmonary delivery of drug-encapsulated nanoparticles of chitosan and its derivatives. In addition, the controversial toxicological effects of chitosan nanoparticles for lung delivery will also be discussed.

  20. Topical Drug Delivery for Chronic Rhinosinusitis

    PubMed Central

    Liang, Jonathan; Lane, Andrew P.

    2013-01-01

    Chronic rhinosinusitis is a multifactorial disorder that may be heterogeneous in presentation and clinical course. While the introduction of endoscopic sinus surgery revolutionized surgical management and has led to significantly improved patient outcomes, medical therapy remains the foundation of long-term care of chronic rhinosinusitis, particularly in surgically recalcitrant cases. A variety of devices and pharmaceutical agents have been developed to apply topical medical therapy to the sinuses, taking advantage of the access provided by endoscopic surgery. The goal of topical therapy is to address the inflammation, infection, and mucociliary dysfunction that underlies the disease. Major factors that impact success include the patient’s sinus anatomy and the dynamics of the delivery device. Despite a growing number of topical treatment options, the evidence-based literature to support their use is limited. In this article, we comprehensively review current delivery methods and the available topical agents. We also discuss biotechnological advances that promise enhanced delivery in the future, and evolving pharmacotherapeutical compounds that may be added to rhinologist’s armamentarium. A complete understand of topical drug delivery is increasingly essential to the management of chronic rhinosinusitis when traditional forms of medical therapy and surgery have failed. PMID:23525506

  1. Multiscale benchmarking of drug delivery vectors.

    PubMed

    Summers, Huw D; Ware, Matthew J; Majithia, Ravish; Meissner, Kenith E; Godin, Biana; Rees, Paul

    2016-10-01

    Cross-system comparisons of drug delivery vectors are essential to ensure optimal design. An in-vitro experimental protocol is presented that separates the role of the delivery vector from that of its cargo in determining the cell response, thus allowing quantitative comparison of different systems. The technique is validated through benchmarking of the dose-response of human fibroblast cells exposed to the cationic molecule, polyethylene imine (PEI); delivered as a free molecule and as a cargo on the surface of CdSe nanoparticles and Silica microparticles. The exposure metrics are converted to a delivered dose with the transport properties of the different scale systems characterized by a delivery time, τ. The benchmarking highlights an agglomeration of the free PEI molecules into micron sized clusters and identifies the metric determining cell death as the total number of PEI molecules presented to cells, determined by the delivery vector dose and the surface density of the cargo. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Chemical coupling of thiolated chitosan to preformed liposomes improves mucoadhesive properties

    PubMed Central

    Gradauer, Kerstin; Vonach, Caroline; Leitinger, Gerd; Kolb, Dagmar; Fröhlich, Eleonore; Roblegg, Eva; Bernkop-Schnürch, Andreas; Prassl, Ruth

    2012-01-01

    Aim To develop mucoadhesive liposomes by anchoring the polymer chitosan-thioglycolic acid (chitosan-TGA) to the liposomal surface to target intestinal mucosal membranes. Methods Liposomes consisting of phosphatidylcholine (POPC) and a maleimide-functionalized lipid were incubated with chitosan-TGA, leading to the formation of a thioether bond between free SH-groups of the polymer and maleimide groups of the liposome. Uncoated and newly generated thiomer-coated liposomes were characterized according to their size, zeta potential, and morphology using photon correlation spectroscopy and transmission electron microscopy. The release behavior of calcitonin and the fluorophore/quencher-couple ANTS/DPX (8-aminonaphthalene-1,3,6-trisulfonic acid/p-xylene-bis- pyridinium bromide) from coated and uncoated liposomes, was investigated over 24 hours in simulated gastric and intestinal fluids. To test the mucoadhesive properties of thiomer-coated and uncoated liposomes in-vitro, we used freshly excised porcine small intestine. Results Liposomes showed a concentration-dependent increase in size – from approximately 167 nm for uncoated liposomes to 439 nm for the highest thiomer concentration used in this study. Likewise, their zeta potentials gradually increased from about −38 mV to +20 mV, clearly indicating an effective coupling of chitosan-TGA to the surface of liposomes. As a result of mucoadhesion tests, we found an almost two-fold increase in the mucoadhesion of coupled liposomes relative to uncoupled ones. With fluorescence microscopy, we saw a tight adherence of coated particles to the intestinal mucus. Conclusion Taken together, our current results indicate that thiomer-coated liposomes possess a high potential to be used as an oral drug-delivery system. PMID:22679365

  3. Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

    PubMed Central

    Moodley, Kovanya; Pillay, Viness; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M. K.; Kumar, Pradeep; Cooppan, Shivaan; Bawa, Priya

    2012-01-01

    Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments. PMID:22312236

  4. Oral drug delivery systems comprising altered geometric configurations for controlled drug delivery.

    PubMed

    Moodley, Kovanya; Pillay, Viness; Choonara, Yahya E; du Toit, Lisa C; Ndesendo, Valence M K; Kumar, Pradeep; Cooppan, Shivaan; Bawa, Priya

    2012-01-01

    Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix(®) multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise(®), which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix(®) as well as "release modules assemblage", which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.

  5. Ultrasound Molecular Imaging and Drug Delivery.

    PubMed

    Caskey, Charles F

    2017-03-02

    Ultrasound is a rapidly advancing field with many emerging diagnostic and therapeutic applications. For diagnostics, new vascular targets are routinely identified and mature technologies are being translated to humans, while other recent innovations may bring about the creation of acoustic reporter genes and micron-scale resolution with ultrasound. As a cancer therapy, ultrasound is being explored as an adjuvant to immune therapies and to deliver acoustically or thermally active drugs to tumor regions. Ultrasound-enhanced delivery across the blood brain barrier (BBB) could potentially be very impactful for brain cancers and neurodegenerative diseases where the BBB often impedes the delivery of therapeutic molecules. In this minireview, we provide an overview of these topics in the field of ultrasound that are especially relevant to the interests of World Molecular Imaging Society.

  6. Drug transport and drug delivery--the Midnight Sun meeting.

    PubMed

    Uchegbu, Ijeoma F

    2004-08-01

    The Midnight Sun Meeting on Drug Transport and Drug Delivery was held on the island of Tromso in northern Norway, where the sun does not set for 2 months during the summer. The meeting was hosted by the University of Tromso's newly established Institute of Pharmacy and the Controlled Release Society (Nordic Chapter). The meeting, attended by approximately 80 delegates from across Europe, showcased recent advances in drug transport through biological barriers, solid-state pharmaceuticals and particulate drug delivery systems. This report will focus on the particulate and solid-state pharmaceuticals sessions, in which lectures were given to demonstrate the benefits in cognitive function associated with omega-3 fish oils, the increase in drug release rates observed on the processing-induced deformation of tablet granules, and the size of polymeric particulates being directly and linearly related to the molecular weight of a polymer. The meeting was held as a single-session event, giving delegates the opportunity to attend all presentations. There was a small poster and exhibitor display, and the meeting attracted sponsorship from a number of companies, namely Polypure AS, Weifa AS, ProBioNeutraceuticals AS, Lipoid GmbH, Clavis Pharma AS and Thermometric AB.

  7. In Situ Forming Polymeric Drug Delivery Systems

    PubMed Central

    Madan, M.; Bajaj, A.; Lewis, S.; Udupa, N.; Baig, J. A.

    2009-01-01

    In situ forming polymeric formulations are drug delivery systems that are in sol form before administration in the body, but once administered, undergo gelation in situ, to form a gel. The formation of gels depends on factors like temperature modulation, pH change, presence of ions and ultra violet irradiation, from which the drug gets released in a sustained and controlled manner. Various polymers that are used for the formulation of in situ gels include gellan gum, alginic acid, xyloglucan, pectin, chitosan, poly(DL-lactic acid), poly(DL-lactide-co-glycolide) and poly-caprolactone. The choice of solvents like water, dimethylsulphoxide, N-methyl pyrrolidone, triacetin and 2-pyrrolidone for these formulations depends on the solubility of polymer used. Mainly in situ gels are administered by oral, ocular, rectal, vaginal, injectable and intraperitoneal routes. The in situ gel forming polymeric formulations offer several advantages like sustained and prolonged action in comparison to conventional drug delivery systems. The article presents a detailed review of these types of polymeric systems, their evaluation, advancements and their commercial formulations. From a manufacturing point of view, the production of such devices is less complex and thus lowers the investment and manufacturing cost. PMID:20490289

  8. Transdermal patch drug delivery interactions with exercise.

    PubMed

    Lenz, Thomas L; Gillespie, Nicole

    2011-03-01

    Transdermal drug delivery systems, such as the transdermal patch, continue to be a popular and convenient way to administer medications. There are currently several medications that use a transdermal patch drug