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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. PMID:19925443

  3. 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

  4. Mucoadhesive and thermogelling systems for vaginal drug delivery.

    PubMed

    Caramella, Carla M; Rossi, Silvia; Ferrari, Franca; Bonferoni, Maria Cristina; Sandri, Giuseppina

    2015-09-15

    This review focuses on two formulation approaches, mucoadhesion and thermogelling, intended for prolonging residence time on vaginal mucosa of medical devices or drug delivery systems, thus improving their efficacy. The review, after a brief description of the vaginal environment and, in particular, of the vaginal secretions that strongly affect in vivo performance of vaginal formulations, deals with the above delivery systems. As for mucoadhesive systems, conventional formulations (gels, tablets, suppositories and emulsions) and novel drug delivery systems (micro-, nano-particles) intended for vaginal administration to achieve either local or systemic effect are reviewed. As for thermogelling systems, poly(ethylene oxide-propylene oxide-ethylene oxide) copolymer-based and chitosan-based formulations are discussed as thermogelling systems. The methods employed for functional characterization of both mucoadhesive and thermogelling drug delivery systems are also briefly described. PMID:25683694

  5. 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. PMID:23321304

  6. 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

    2005-11-01

    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. PMID:16169120

  7. 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

  8. Formulation of mucoadhesive gastric retentive drug delivery using thiolated xyloglucan.

    PubMed

    Bhalekar, Mangesh R; Bargaje, Rajesh V; Upadhaya, Prashant G; Madgulkar, Ashwini R; Kshirsagar, Sanjay J

    2016-01-20

    Tamarind seed xyloglucan is a polymer reported to possess mucoadhesive property. In the present work, role of cysteine derivative of tamarind seed polysaccharide (thiomer) to enhance the mucoadhesion and its influence on drug permeation has been studied. The xyloglucan was first chemically modified to carboxymethyl derivative which was further converted to thiomer by conjugation with cysteine in presence of a coupling agent, EDAC. The matrix tablets of simvastatin prepared using thiomer demonstrated drug release retardation, increased mucoadhesion force and increased ex vivo permeation, the same were proportional to the increase in the amount of thiomer. The in vivo residence of thiomer placebo was more than 7h in rabbit. Pharmacokinetic evaluation in rabbits indicated higher AUC for the formulation with highest content of thiomer and level 'A' correlation could be established from the generated dissolution and bioavailability data. PMID:26572385

  9. 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

  10. Modified alginate beads for mucoadhesive drug delivery system: an updated review of patents.

    PubMed

    Swain, Suryakanta; Behera, Aurobinda; Beg, Sarwar; Patra, Chinam N; Dinda, Subash C; Sruti, Jammula; Rao, Muddana E B

    2012-12-01

    Pharmaceutical research and inventions are increasingly developed for the design of an ideal dosage regimen in drug therapy of many diseases, which attains therapeutic concentration of drug in plasma and maintains it constant for the entire duration of treatment and also minimizes the side effects. Recent trends in pharmaceutical technology indicated that mucoadhesive micro particle and modified alginate beads as drug delivery system especially suitable for achieving delivery of drug in a predetermined rate locally or systemically for a prolonged period of time. The release of drug from microparticle depends on a variety of factors including carrier used to form the micro particle and amount of drug contained in them. The main aim of the present review is to explain the various theories, mechanisms, advanced mucoadhesive polymers, various delivery approaches, methodologies for developing a mucoadhesive micro-particle and modified alginate beads formulation, in vitro, ex vivo and in vivo characterization. Apart from this, an innovative test method that is biacore is highlighted in this review to measure the mucoadhesive strength. This review is also briefly explained about the updated patenting system for the development of micro-particle and modified alginate beads as drug delivery system. PMID:22734868

  11. Natural mucoadhesive microspheres of Abelmoschus esculentus polysaccharide as a new carrier for nasal drug delivery.

    PubMed

    Sharma, Nitin; Kulkarni, Giriraj T; Sharma, Anjana; Bhatnagar, Aseem; Kumar, Neeraj

    2013-01-01

    This work describes the preparation and evaluation of mucoadhesive microspheres, using Abelmoschus esculentus polysaccharide as a novel carrier for safe and effective delivery of rizatriptan benzoate into nasal cavity. The polysaccharide was extracted from the fruit of A. esculentus and mucoadhesive microspheres were prepared by emulsification, followed by crosslinking using epichlorohydrin. Prepared microspheres were evaluated for size, morphology, swelling properties, mucoadhesive strength, encapsulation efficiency and drug release. Microspheres were found to release 50% of drug within 15 min and rest of the drug was released within 60 min. The drug release was found to decrease with increasing concentration of polysaccharide. To determine the retention time of the microspheres in the nasal cavity of rabbits, the microspheres were radiolabelled with (99m)Tc and subjected to gamma scintigraphy. The results showed a significant improvement in the nasal retention of the microspheres as compared to the aqueous solution of radiolabelled free-drug. PMID:23379506

  12. Phenylboronic-Acid-Based Polymeric Micelles for Mucoadhesive Anterior Segment Ocular Drug Delivery.

    PubMed

    Prosperi-Porta, Graeme; Kedzior, Stephanie; Muirhead, Benjamin; Sheardown, Heather

    2016-04-11

    Topical drug delivery to the front of the eye is extremely inefficient due to effective natural protection mechanisms such as precorneal tear turnover and the relative impermeability of the cornea and sclera tissues. This causes low ocular drug bioavailability, requiring large frequent doses that result in high systemic exposure and side effects. Mucoadhesive drug delivery systems have the potential to improve topical drug delivery by increasing pharmaceutical bioavailability on the anterior eye surface. We report the synthesis and characterization of a series of poly(l-lactide)-b-poly(methacrylic acid-co-3-acrylamidophenylboronic acid) block copolymer micelles for use as mucoadhesive drug delivery vehicles. Micelle properties, drug release rates, and mucoadhesion were shown to depend on phenylboronic acid content. The micelles showed low in vitro cytotoxicity against human corneal epithelial cells and undetectable acute in vivo ocular irritation in Sprague-Dawley rats, suggesting good biocompatibility with the corneal surface. The micelles show the potential to significantly improve the bioavailability of topically applied ophthalmic drugs, which could reduce dosage, frequency of administration, and unintentional systemic exposure. This would greatly improve the delivery of the ocular drugs such as the potent immunosuppressive cyclosporine A used in the treatment of severe dry eye disease. PMID:26963738

  13. 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

  14. Mucoadhesive acrylated block copolymers micelles for the delivery of hydrophobic drugs.

    PubMed

    Eshel-Green, Tal; Bianco-Peled, Havazelet

    2016-03-01

    Blockpolymer micelles having acrylated end groups were fabricated for the development of mucoadhesive drug loaded vehicle. The critical micelle concentration (CMC) of Pluronic(®) F127 modified with acrylate end groups (F127DA) was found to be similar to that of the unmodified Pluronic(®) F127 (F127). Small angle X-ray scattering verified existence of micelles with an inner core of 4.9±0.2 and 5.5±0.3 for F127 and F127DA respectively. Indomethacin, a hydrophobic drug, was incorporated into the micelles using the thin-film hydration method. In vitro drug release assay demonstrated that the micelles sustained the release of the drug in comparison with free drug in solution. Several methods were used for mucoadhesion evaluation. Viscosity profiling was performed by shear rate sweep experiment of hydrated commercial mucin, F127 or F127DA, and combination of both mucin and a copolymer. Elevated viscosity was achieved for acrylated micelles with mucin compared to mixtures of non-acrylated micelles with mucin. The mucoadhesivity of the acrylated micelles was further characterized using nuclear magnetic resonance (NMR); data affirmed the Michael type addition reaction occurred between acrylates on the micelles corona and thiols present in the mucin. SAXS scattering data further showed a modification in the scattering of F127DA micelles with the addition of pig gastric mucin. Cryo-transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS) data detected increase in the aggregates size while using acrylated micelles enhance mucoadhesion. Thus acrylated F127DA micelles were found to be mucoadhesive, and a suitable and preferred candidate for micellar drug delivery to mucosal surfaces. PMID:26700232

  15. 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

  16. 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. PMID:26636069

  17. 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

  18. 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.

  19. Mucoadhesive Chitosan Derivatives as Novel Drug Carriers.

    PubMed

    Islam, Mohammad Ariful; Park, Tae-Eun; Reesor, Emma; Cherukula, Kondareddy; Hasan, Anwarul; Firdous, Jannatul; Singh, Bijay; Kang, Sang-Kee; Choi, Yun-Jaie; Park, In-Kyu; Cho, Chong-Su

    2015-01-01

    Chitosan on its own is a well-established natural polymer and is widely regarded as a biodegradable, biocompatible and nontoxic material for drug delivery applications. Although unmodified chitosan has some mucoadhesive properties on its own, its bioavailability is limited due to its short retention time in the body. Moreover, the high solubility of chitosan at acidic pH levels limits its use for mucosal drug delivery (especially through the oral route). Chemically-modified mucoadhesive chitosan, especially thiolated chitosan, has arisen as an alternative to create novel mucosal drug delivery systems. The mucoadhesive properties that are conferred to the thiolated chitosan certainly set this novel class of second or third-generation thiomers apart. To understand the significance of mucoadhesive chitosan, we first present the mechanism of mucoadhesion and provide comprehensive coverage of description of a variety of chemical modifications to prepare mucoadhesive thiolated chitosan derivatives. We then present the plethora of applications of these modified chitosan variants in a wide range of drug delivery fields, including the delivery of antigens, proteins and genes through a variety of routes, including oral, nasal, pulmonary, vaginal and others. By presenting the range of applications for mucoadhesive chitosan drug carriers we herein demonstrate that chemically-modified thiolated chitosan is a versatile and effective material for a new class of drug delivery vehicles. PMID:26323422

  20. 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

  1. Mucoadhesive microparticulates based on polysaccharide for target dual drug delivery of 5-aminosalicylic acid and curcumin to inflamed colon.

    PubMed

    Duan, Haogang; Lü, Shaoyu; Gao, Chunmei; Bai, Xiao; Qin, Hongyan; Wei, Yuhui; Wu, Xin'an; Liu, Mingzhu

    2016-09-01

    In this work, thiolated chitosan/alginate composite microparticulates (CMPs) coated by Eudragit S-100 were developed for colon-specific delivery of 5-aminosalicylic acid (5-ASA) and curcumin (CUR), and the use of it as a multi drug delivery system for the treatment of colitis. The physicochemical properties of the CMPs were evaluated. In vitro release was performed in gradually pH-changing medium simulating the conditions of different parts of GIT, and the results showed that the Eudragit S-100 coating has a pH-sensitive release property, which can avoid drug being released at a pH lower than 7. An everted sac method was used to evaluate the mucoadhesion of CMPs. Ex vivo mucoadhesive tests showed CMPs have excellent mucosa adhesion for the colonic mucosa of rats. In vivo treatment effect of enteric microparticulates systems was evaluated in colitis rats. The results showed superior therapeutic efficiency of this drug delivery system for the colitis rats induced by TNBS. Therefore, the enteric microparticulates systems combined the properties of pH dependent delivery, mucoadhesive, and control release, and could be an available tool for the treatment of human inflammatory bowel disease. PMID:27239905

  2. Exploitation of novel gum Prunus cerasoides as mucoadhesive beads for a controlled-release drug delivery.

    PubMed

    Seelan, T Veenus; Kumari, Henry Linda Jeeva; Kishore, Narra; Selvamani, Palanisamy; Lalhlenmawia, H; Thanzami, K; Pachuau, Lalduhsanga; Ruckmani, Kandasamy

    2016-04-01

    The present study deals with the formulation of pH-sensitive mucoadhesive beads using natural gum isolated from Prunus cerasoides (PC) in combination with sodium alginate (SA) for the controlled release of diclofenac sodium (DS). PC and SA composite (PC-SA), DS loaded SA (DS-SA) and DS loaded PC-SA (DS-PC-SA) beads were prepared by ionotropic gelation method. The absence of interaction between DS and PC-SA was shown by FTIR, DSC and TGA analyses. The optimized DS-PC-SA formulation exhibited mucoadhesive property and the controlled release of DS was achieved 68% in 12h. The in vitro release kinetics follows zero order with anomalous diffusion mechanism. Therefore, the formulated mucoadhesive beads with the novel gum are preferable for the controlled release of DS by prolonging the residence time of the drug in the gastrointestinal tract, overcoming the problems associated with the immediate release dosage forms of DS. PMID:26772921

  3. The physicodynamic properties of mucoadhesive polymeric films developed as female controlled drug delivery system.

    PubMed

    Yoo, Jin-Wook; Dharmala, Kiran; Lee, Chi H

    2006-02-17

    To develop an efficient female controlled drug delivery system (FcDDS) against sexually transmitted diseases (STDs), the polymeric films containing sodium dodecyl sulfate (SDS) were prepared with various compositions of Carbopol 934P, hydroxypropyl methylcellulose (HPMC) and polyethylene glycol (PEG). The physicochemical properties of mucoadhesive polymeric films, such as tensile strength, contact angle, swelling ratio and erosion rate in a vaginal fluid stimulant (VFS), were characterized. In addition, the drug release profile of SDS from the films and mucosal residence time were evaluated using a simulated dynamic vaginal system. It was demonstrated that the films made of Carbopol, HPMC and PEG were colorless, thin and soft and had proper physicodynamic properties for FcDDS. An increase in Carbopol content elevated tensile strength and swelling ratio but decreased the contact angle, erosion rate and the SDS release rate from the films. The films containing 0.25% (w/v) PEG as well as 0.75% (w/v) of combining Carbopol and HPMC remained on the vaginal tissue for up to 6h. The films containing the ratio of Carbopol:HPMC:PEG=1.5:1.5:1 and 1:2:1 seem to be optimal compositions for FcDDS, as they showed good peelability, relatively high swelling index and moderate tensile strength, and achieved the target release rate of SDS for 6h. PMID:16376036

  4. 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

  5. Synthesis and characterization of pH tolerant and mucoadhesive (thiol-polyethylene glycol) chitosan graft polymer for drug delivery.

    PubMed

    Hauptstein, Sabine; Bonengel, Sonja; Griessinger, Julia; Bernkop-Schnürch, Andreas

    2014-02-01

    The objective of this study was to generate a water-soluble thiolated chitosan to enable the permeation-enhancing effect of chitosan at pH of at least 5.5 without losing the advantages of improved mucoadhesive properties. Therefore, the thiol-bearing polyoxyethylene ligand {O-(3-carboxylpropyl)-O'-[2-[3-mercaptopropionylamino)ethyl]-polyethyleneglycol} was conjugated via amide bond formation to the amino group of chitosan. Resulting novel chitosan derivative (Chito-PEG-SH) exhibited 250 μmol free thiol groups per gram polymer. By the attachment of the thiol-bearing PEG ligand, an improvement of permeation-enhancing effect on rat intestine (2.7-fold improvement) as well as on a Caco-2 monolayer model (1.9-fold improvement) could be found. Cytotoxicity studies on Caco-2 cells revealed no change in biocompatibility. Mucoadhesion was improved 3.1-fold by the formation of disulfide bonds with mucus glycoproteins. The mucoadhesive effect of Chito-PEG-SH turned out to be similar to thiolated chitosan and more pronounced than mucoadhesive properties of unmodified chitosan. The graft polymer is soluble in water and aqueous solutions over a broad pH range. In aqueous media, the novel polymer does not precipitate at pH of 8.6 or less. According to these results, Chito-PEG-SH might show potential as auxiliary agent in oral drug delivery where its solubility even up to pH 8 is likely beneficial. PMID:24382680

  6. Preparation and Evaluation of Mucoadhesive Beads/Discs of Alginate and Algino-Pectinate of Piroxicam for Colon-Specific Drug Delivery Via Oral Route

    PubMed Central

    Jelvehgari, Mitra; Mobaraki, Vajihe; Montazam, Seyed Hassan

    2014-01-01

    Background: Targeted drug delivery to colon would ensure direct treatment at the disease site, decrease in dose administration and reduction side effects improved drug utilization. Objective: The purpose of this research was to decrease gastric side effects of piroxicam by formulating microspheres of alginate and algino-pectinate beads of the drug. Materials and Methods: Ionotropic gelation was used to entrap piroxicam into alginate and algino-pectinate mucoadhesive microspheres as a potential drug carrier for oral delivery of piroxicam. Microparticles with different drug to polymers ratio were prepared and characterized by encapsulation efficiency, particle size, DSC (differential scanning calorimetric), mucoadhesive property, gastroretentive time and drug release studies. Results: The best drug to polymer ratio of microparticles was 1:2.5 (F1) with Na-Alg and 1:7.5 (F4) with Alg-Na with pectin, respectively. The microparticles F1 and F4 showed 28.80%, 50.01% loading efficiency, 82.57%, 82.31% production yield and 945.4, 899.91 µm mean particle size. DSC showed stable character of piroxicam in drug-loaded microparticles and revealed amorphous form. It was found that microparticles (Na-Alg) prepared had faster release and microparticles (Alg-Na and pectin mixture) prepared had slower release than untreated piroxicam (P < 0.05). Microparticles (mixture of Na-Alg and pectin) exhibited very good percentage of mucoadhesion and flowability properties. Mucoadhesion strength and retention time study showed better retention of piroxicam microparticles in intestine. Besides, there was a significant higher retention of mucoadhesive microparticles in upper GI tract. Conclusions: Algino-pectinate mucoadhesive formulations exhibited promising properties of a sustained release form for piroxicam and provided distinct tissue protection in stomach. PMID:25625047

  7. Mucoadhesive beads of gellan gum/pectin intended to controlled delivery of drugs.

    PubMed

    Prezotti, Fabíola Garavello; Cury, Beatriz Stringhetti Ferreira; Evangelista, Raul Cesar

    2014-11-26

    Gellan gum/pectin beads were prepared by ionotropic gelation, using Al(3+) as crosslinker. High yield (92.76%) and entrapment efficiency (52.22-88.78%) were reached. Beads exhibited high circularity (0.730-0.849) and size between 728.95 and 924.56 μm. Particle size and circularity was increased by raising polymer and crosslinker concentrations. Polymers ratio did not influence beads properties. The materials stability and the absence of drug-polymers interactions were evidenced by thermal analysis and FTIR. The high beads mucoadhesiveness was evidenced by in vitro and ex vivo tests. The erosion of beads was greater in acid media while swelling was more pronounced in pH 7.4. Drug release was dependent on pH in which samples 11H1-3, 11H1-5 and 41H1-3 released only 34%, 20% and 22% of ketoprofen in pH 1.2, while in pH 7.4 the drug release was sustained up to 360 min. Korsmeyer-Peppas model demonstrated that drug release occurred according to super case-II transport. PMID:25256487

  8. Design and evaluation of mucoadhesive beads of glipizide as a controlled release drug delivery system.

    PubMed

    Bera, K; Khanam, J; Mohanraj, K P; Mazumder, B

    2014-01-01

    The present work aims at the development of a low-cost controlled release system of glipizide beads embedded in pectin to overcome the problem of frequent dosing of drug. The method of preparation has been optimised by experimental design to achieve satisfactory responses with respect to controlling variables. The controlling variables are X1, drug-polymer ratio; X2, surfactant concentration and X3, isooctane-acetone ratio. The most effective combination is X1(1:6), X2(1%), X3(50:50). Various parameters such as mucoadhesivity and swellability of beads, characterisation, dissolution, stability, ex vivo absorption and in vivo (Oral glucose tolerance test in rat) studies were performed with the optimised product. The optimised product was found quiet satisfactory that showed yield of 86.78%, drug entrapment efficiency (DEE) of 87.38% and drug release was extended up to 18 h. The present formulation of glipizide is a promising multiparticulate system of glipizide with significant hypoglycemic effect, and moreover it was prepared rapidly with ease. PMID:24047213

  9. 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. PMID:21453255

  10. 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. PMID:24669975

  11. Comparative study of nanosized cross-linked sodium-, linear sodium- and zinc-hyaluronate as potential ocular mucoadhesive drug delivery systems.

    PubMed

    Horvát, Gabriella; Budai-Szűcs, Mária; Berkó, Szilvia; Szabó-Révész, Piroska; Soós, Judit; Facskó, Andrea; Maroda, Mónika; Mori, Michela; Sandri, Giuseppina; Bonferoni, Maria Cristina; Caramella, Carla; Csányi, Erzsébet

    2015-10-15

    Hyaluronic acid (HA) and its derivatives play important roles in many fields of therapy, such as arthritis treatment, plastic surgery, dermatology, otology, ophthalmology, etc. With a view to increase the beneficial properties of HA in ocular drug delivery, many types of chemical structural modifications have been performed. In the course of our research work, we characterized nanosized cross-linked - (CLNaHA), linear sodium hyaluronate (NaHA) and zinc-hyaluronate (ZnHA), as potential ocular drug delivery systems. The aim was to determine the influence of the structure on biocompatibility, mucoadhesion and drug release. The structure was characterized by means of rheology. The cytotoxicity of the samples was determined on rabbit corneal epithelial cells (RCE) by the MTT test. Mucoadhesion measurements were made by a rheological method in vitro and by tensile tests in vitro and ex vivo. The release of sodium diclofenac, a frequently used non-steroidal anti-inflammatory drug with low bioavailability, from the gels was determined with a vertical Franz diffusion cell. The results demonstrated that all three derivatives have adequate mucoadhesive properties and their rapid drug release profiles are beneficial in ocular therapy. Thanks to these properties, the bioavailability of the ophthalmic preparations can be increased, especially with the application of CLNaHA. PMID:26319587

  12. 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. PMID:26253804

  13. Feasibility Investigation of Cellulose Polymers for Mucoadhesive Nasal Drug Delivery Applications.

    PubMed

    Hansen, Kellisa; Kim, Gwangseong; Desai, Kashappa-Goud H; Patel, Hiren; Olsen, Karl F; Curtis-Fisk, Jaime; Tocce, Elizabeth; Jordan, Susan; Schwendeman, Steven P

    2015-08-01

    The feasibility of various cellulose polymer derivatives, including methylcellulose (MC), hydroxypropyl methylcellulose (HPMC), sodium-carboxymethylcellulose (sodium-CMC), and cationic-hydroxyethylcellulose (cationic-HEC), for use as an excipient to enhance drug delivery in nasal spray formulations was investigated. Three main parameters for evaluating the polymers in nasal drug delivery applications include rheology, ciliary beat frequency (CBF), and permeation across nasal tissue. Reversible thermally induced viscosity enhancement was observed at near nasal physiological temperature when cellulose derivatives were combined with an additional excipient, poly(vinyl caprolactam)-poly(vinyl acetate)-poly(ethylene glycol) graft copolymer (PVCL-PVA-PEG). Cationic-HEC was shown to enhance acyclovir permeation across the nasal mucosa. None of the tested cellulosic polymers caused any adverse effects on porcine nasal tissues and cells, as assessed by alterations in CBF. Upon an increase in polymer concentration, a reduction in CBF was observed when ciliated cells were immersed in the polymer solution, and this decrease returned to baseline when the polymer was removed. While each cellulose derivative exhibited unique advantages for nasal drug delivery applications, none stood out on their own to improve more than one of the performance characteristics examined. Hence, these data may be useful for the development of new cellulose derivatives in nasal drug formulations. PMID:26097994

  14. Synthesis and characterization of thiolated β-cyclodextrin as a novel mucoadhesive excipient for intra-oral drug delivery.

    PubMed

    Ijaz, Muhammad; Matuszczak, Barbara; Rahmat, Deni; Mahmood, Arshad; Bonengel, Sonja; Hussain, Shah; Huck, Christian W; Bernkop-Schnürch, Andreas

    2015-11-01

    The objective of the present study was to synthesize and characterize cysteamine conjugated β-cyclodextrin (β-CD-Cys) as a novel mucoadhesive oligomeric excipient for intra-oral drug delivery. β-CD-Cys conjugates were obtained in a two-step synthetic pathway, whereby, vicinal diol groups of the oligomer were oxidized using increasing concentrations of sodium-per-iodate (NaIO4), prior to the covalent coupling of cysteamine via reductive amination. Quantification of immobilized thiol groups through Ellman's test revealed 561.56 ± 81 μmol/g, 1054.26 ± 131 μmol/g and 1783.92 ± 201 μmol/g of free thiol groups attached to the oligomer backbone depending on the extent of oxidation. β-CD-Cys conjugates at concentrations of 0.5% (m/v) showed no toxic effects on Caco-2 cells within 72 h. Furthermore, β-CD-Cys conjugates displayed a 4-fold improved water solubility compared to the parent oligomer. β-CD-Cys conjugates (β-CD-Cys561, β-CD-Cys1054 and β-CD-Cys1783) showed 2.86-, 15.09- and 49.08-fold improved retention time on porcine intestinal mucosa and 9.66-, 16.43- and 34.51-fold improved on the porcine buccal mucosa, respectively. Formation of inclusion complexes of miconazole nitrate and β-CD-Cys1054 resulted in 150-fold increased solubility of miconazole nitrate. According to these results, it seems that β-CD-Cys conjugates might provide a new promising tool for delivery of poorly water soluble therapeutic agents, such as miconazole nitrate for intra-oral delivery. PMID:26256340

  15. Cellulose triacetate films obtained from sugarcane bagasse: Evaluation as coating and mucoadhesive material for drug delivery systems.

    PubMed

    Ribeiro, Sabrina Dias; Guimes, Rodrigues Filho; Meneguin, Andréia Bagliotti; Prezotti, Fabíola Garavello; Boni, Fernanda Isadora; Cury, Beatriz Stringhetti Ferreira; Gremião, Maria Palmira Daflon

    2016-11-01

    Cellulose triacetate (CTA) films were produced from cellulose extracted from sugarcane bagasse. The films were characterized using scanning electron microscopy (SEM), water vapor permeability (WVP), mechanical properties (MP), enzymatic digestion (ED), and mucoadhesive properties evaluation (MPE). WVP showed that more concentrated films have higher values; asymmetric films had higher values than symmetric films. MP showed that symmetric membranes are more resistant than asymmetric ones. All films presented high mucoadhesiveness. From the WVP and MP results, a symmetric membrane with 6.5% CTA was selected for the coating of gellan gum (GG) particles incorporating ketoprofen (KET). Thermogravimetric analysis (TGA) showed that the CTA coating does not influence the thermal stability of the particles. Coated particles released 100% of the KET in 24h, while uncoated particles released the same amount in 4h. The results highlight the CTA potential in the development of new controlled oral delivery systems. PMID:27516328

  16. 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. PMID:26864536

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

    PubMed Central

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

    2014-01-01

    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. PMID:26579378

  18. A novel riboflavin gastro-mucoadhesive delivery system based on ion-exchange fiber.

    PubMed

    Yao, Huimin; Xu, Lu; Han, Fei; Che, Xin; Dong, Yang; Wei, Min; Guan, Jiao; Shi, Xiaolei; Li, Sanming

    2008-11-19

    A novel gastro-mucoadhesive delivery system based on ion-exchange fiber has been developed. Riboflavin-5'-phosphate sodium salt (RF5P), which is site-specifically absorbed from the upper gastrointestinal tract, was used as model drug. A modified dissolution system, which can also be called 'flow through diffusion cell' (FTDC), was used to study the drug release from the drug fibers. Gastrointestinal transit studies of the RF5P fiber complexes in rats and gamma imaging study in volunteer was carried out to evaluate the gastro-retentive behavior of the fiber. The pharmacokinetic profile and parameters of riboflavin via analysis of urinary excretion of riboflavin on man were measured. Study on rat and man provide evidence for the validity of the hypothesis that the drug fiber provided good mucoadhesive properties in vivo and should therefore be of considerable interest for the development of future mucoadhesive oral drug delivery dosage forms. PMID:18761065

  19. Development and in vitro evaluation of diclofenac sodium loaded mucoadhesive microsphere with natural gum for sustained delivery.

    PubMed

    Amin, Md Lutful; Jesmeen, Tasbira; Sutradhar, Kumar Bishwajit; Mannan, Md Abdul

    2013-12-01

    The objective of this study was to develop and evaluate mucoadhesive microsphere of diclofenac sodium with natural gums for sustained delivery. Guar gum and tragacanth were used along with sodium alginate as mucoadhesive polymers. Microspheres were formulated using orifice-ionic gelation method. Particle size, surface morphology, swelling study and drug entrapment efficiency of the prepared microspheres were determined. In vitro evaluation was carried out comprising of mucoadhesion and drug release study. The prepared microspheres were discrete and free flowing. Sodium alginate and natural gum, at a ratio of 1:0.25, showed good mucoadhesive property and they had high drug entrapment efficiencies. They also exhibited the best rate retarding effect among all the formulations. Drug entrapment efficiency of all the microspheres ranged from 80.42% to 91.67%. An inverse relationship was found between extent of crosslinking and drug release rate. Release rate was slow and extended in case of the formulations of 1:0.25 ratio (F1 and F3), releasing 68.36% and 70.56% drug respectively after 8 hours. Tragacanth-containing microspheres of F1 showed superiority over other formulations, with best mucoadhesive and rate retarding profile. The correlation value (r(2)) indicated that the drug release of all the formulations followed Higuchi's model. Overall, the results indicated that mucoadhesive microspheres containing natural gum can be promising in terms of prolonged delivery with good mucoadhesive action, targeting the absorption site to thrive oral drug delivery. PMID:23937160

  20. 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

  1. 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. PMID:26997698

  2. A mucoadhesive in situ gel delivery system for paclitaxel.

    PubMed

    Jauhari, Saurabh; Dash, Alekha K

    2006-01-01

    MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyceryl monooleate (GMO) in 0.33M citric acid containing PTX. The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at drug loads of 0.18%, 0.30%, and 0.54% (wt/wt), in Sorensen's phosphate buffer (pH 7.4) at 37 degrees C. Different mucin-producing cell lines (Calu-3>Caco-2) were selected for PTX transport studies. Transport of PTX from solution and gel delivery system was performed in side by side diffusion chambers from apical to basal (A-B) and basal to apical (B-A) directions. In vitro release studies revealed that within 4 hours, only 7.61% +/- 0.19%, 12.0% +/- 0.98%, 31.7% +/- 0.40% of PTX were released from 0.18%, 0.30%, and 0.54% drug-loaded gel formulation, respectively, in absence of Tween 80. However, in presence of surfactant (0.05% wt/vol) in the dissolution medium, percentages of PTX released were 28.1% +/- 4.35%, 44.2% +/- 6.35%, and 97.1% +/- 1.22%, respectively. Paclitaxel has shown a polarized transport in all the cell monolayers with B-A transport 2 to 4 times higher than in the A-B direction. The highest mucin-producing cell line (Calu-3) has shown the lowest percentage of PTX transport from gels as compared with Caco-2 cells. Transport of PTX from mucoadhesive gels was shown to be influenced by the mucin-producing capability of cell. PMID:16796370

  3. 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. PMID:27246816

  4. 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

  5. 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

  6. 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. PMID:24579883

  7. 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

  8. 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

  9. Topical delivery of a Rho-kinase inhibitor to the cornea via mucoadhesive film.

    PubMed

    Chan, Wendy; Akhbanbetova, Alina; Quantock, Andrew J; Heard, Charles M

    2016-08-25

    The application of inhibitors of the Rho kinase pathway (ROCK inhibitors) to the surface of the eye in the form of eyedrops has beneficial effects which aid the recovery of diseased or injured endothelial cells that line the inner surface of the cornea. The aim of this study was to test the plausibility of delivering a selective ROCK inhibitor, Y-27632, to the cornea using a thin polymeric film. Mucoadhesive polymeric thin films were prepared incorporating Y-27632 and diffusional release into PBS was determined. Topical ocular delivery from the applied film was investigated using freshly excised porcine eyes and eyedrops of equivalent concentration acted as comparators; after 24h the formulations were removed and the corneas extracted. Drug-loaded thin polymeric films, with high clarity and pliability were produced. ROCK inhibitor Y-27632 was weakly retained within the film, with release attaining equilibrium after 1h. This in turn facilitated its rapid ocular delivery, and an approximately three-fold greater penetration of Y-27632 into cryoprobe-treated corneas was observed from the thin film (p<0.01) compared to eyedrops. These findings support the further development of ROCK inhibitor delivery to the cornea via release from thin mucoadhesive films to treat vision loss cause by corneal endothelial dysfunction. PMID:27196964

  10. Mucoadhesive controlled release ciprofloxacin nanoparticles for pulmonary delivery

    NASA Astrophysics Data System (ADS)

    Mudumba, Sujata S.

    Controlled release of drugs to the lungs is an interesting and evolving field of research. The influence of physicochemical properties of nanoparticles on the controlled release of ciprofloxacin and in-vivo pharmacokinetics following pulmonary administration was evaluated. The physicochemical properties had an effect on encapsulation efficiency and surface charge, but no significant effect on particle size. The in-vitro release profiles of ciprofloxacin in phosphate buffered saline showed small differences over the range of physicochemical properties evaluated. The physicochemical properties of ciprofloxacin nanoparticles resulted in variable and unreliable nebulizer output using a vibrating mesh nebulizer whereas the impact on the aerosol properties of a jet nebulizer was negligible. Addition of mucoadhesive polymers in the nanoparticles had a three-fold increase in apparent half-life in rats by releasing ciprofloxacin over an extended release period on the surfaces of the lungs.

  11. Thiolated Cyclodextrin: Development of a Mucoadhesive Vaginal Delivery System for Acyclovir.

    PubMed

    Ijaz, Muhammad; Griessinger, Julia Anita; Mahmood, Arshad; Laffleur, Flavia; Bernkop-Schnürch, Andreas

    2016-05-01

    The objective of this study was the development of a mucoadhesive vaginal delivery system for acyclovir (Acv). Sodium-per-iodate (NaIO4) was used to introduce aldehyde substructures into beta-cyclodextrin (β-CD) by oxidative cleavage of vicinal diol bonds. Cysteamine was covalently attached to β-CD-CHO via reductive amination. Ellman's reagent was utilized for quantification of free thiol groups attached and resazurin assay was used for cytotoxicity studies. Mucoadhesive properties were evaluated on porcine vaginal mucosa in comparison to intestinal mucosa. Quantification of thiol groups revealed 851.84 ± 107, 1040.44 ± 132, and 1563.72 ± 171 μmol/g of free thiol groups attached to the β-CD-SH851, β-CD-SH1040, and β-CD-SH1563, respectively. β-CD-SH derivatives at concentrations of 0.5% (m/v) did not show significant reduction of viability of Caco-2 cells within 24 h. Furthermore, water solubility of β-CD-SH1563 was improved 7.6-fold in comparison to unmodified β-CD. β-CD-SH851, β-CD-SH1040, and β-CD-SH1563 showed 5.84-, 15.95-, and 17.14-fold improved mucoadhesive properties on porcine vaginal mucosa and 3-, 12.47-, and 32.13-fold on porcine intestinal mucosa, respectively. Inclusion complex of Acv with β-CD-SH1563 resulted in significantly improved drug dissolution. According to the results, β-CD-SH derivatives might be promising new tools for local vaginal delivery of Acv. PMID:27112405

  12. 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

  13. Polymeric mucoadhesive tablets for topical or systemic buccal delivery of clonazepam: Effect of cyclodextrin complexation.

    PubMed

    Mura, P; Cirri, M; Mennini, N; Casella, G; Maestrelli, F

    2016-11-01

    Two kinds of mucoadhesive buccal tablets of clonazepam (CLZ) were developed to provide, a prolonged local or systemic delivery respectively. Tablets prepared by direct compression of combinations of different polymers were tested for swelling, erosion and residence time properties. Carbopol 971P/hydroxypropylmethylcellulose and Poloxamer/chitosan mixtures were the best and were selected for drug loading. The effect of CLZ complexation with different cyclodextrins was investigated. Randomly-methylated-βCD (RAMEßCD) was the most effective, allowing 100% drug released increase from local-delivery buccal tablets. Kollicoat was the best among the tested backing-layers, assuring a unidirectional release from systemic-delivery buccal tablets (<0.8% drug released in simulated saliva after 24h). In vitro permeation studies from coated-tablets showed that CLZ loading as RAMEßCD-coground enabled a 5-times increase in drug flux and permeability. Therefore, complexation with RAMEßCD was a successful strategy to improve the CLZ performance from buccal tablets for both local or systemic action. PMID:27516327

  14. Transmucosal sustained-delivery of chlorpheniramine maleate in rabbits using a novel, natural mucoadhesive gum as an excipient in buccal tablets.

    PubMed

    Alur, H H; Pather, S I; Mitra, A K; Johnston, T P

    1999-10-15

    The objective of this study was to evaluate the gum from Hakea gibbosa (Hakea) as a sustained-release and mucoadhesive component in buccal tablets following their application to the buccal mucosa of rabbits. Flat-faced core tablets containing either 22 or 32 mg of Hakea and 40 or 25 mg of chlorpheniramine maleate (CPM) per tablet with either sodium bicarbonate or tartaric acid in a 1:1.5 molar ratio were formulated using a direct compression technique and were coated with Cutina(R) on all but one face. The resulting plasma CPM concentration versus time profiles were determined following buccal application of the tablets in rabbits. The strength of mucoadhesion of the tablets was also quantitated in terms of the force of detachment as a function of time. Following the application of the mucoadhesive buccal tablets, the following values for several pharmacokinetic parameters were obtained. The force of detachment for the mucoadhesive buccal tablets containing 22 mg of Hakea and either 25 and 40 mg CPM, and 32 mg Hakea and 40 mg CPM increased from 1.64+/-0.47 to 7.32+/-0.34 N, 1.67+/-0.30 to 7.21+/-0.36 N, and 2.93+/-0.73 to 7.92+/-0.60 N, respectively from 5 to 90 min following application to excised intestinal mucosa. Addition of either sodium bicarbonate or tartaric acid, as well as higher amounts of CPM, did not affect the mucoadhesive bond strength. These results demonstrate that the novel, natural gum, H. gibbosa, may not only be used to sustain the release of CPM from a unidirectional-release buccal tablet, but also demonstrate that the tablets are sufficiently mucoadhesive for clinical application. The mucoadhesive strength as measured by the force of detachment, can be modulated by altering the amount of Hakea in the tablet. The mucoadhesive buccal tablets evaluated represent an improved transbuccal delivery system for conventional drug substances. PMID:10528077

  15. 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. PMID:27106502

  16. Mucoadhesive buccal films containing phospholipid-bile salts-mixed micelles as an effective carrier for Cucurbitacin B delivery.

    PubMed

    Lv, Qingyuan; Shen, Chengying; Li, Xianyi; Shen, Baode; Yu, Chao; Xu, Pinghua; Xu, He; Han, Jin; Yuan, Hailong

    2015-05-01

    Cucurbitacin B (Cu B), a potent anti-cancer agent, suffers with the problems of water-insoluble, gastrointestinal side effects and non-specific toxicity via oral administration and drawbacks in patient's compliance and acceptance through injections. An integration of nanoscale carriers with mucoadhesive buccal films drug delivery system would resolve these issues effectively with greater therapeutic benefits and clinical significance. Thus, the drug loaded mucoadhesive buccal film was developed and characterized in this study and the carboxymethyl chitosan (CCS) was chosen as a bioadhesive polymer, glycerol was chosen as a plasticizer and phospholipid-bile salts-mixed micelles (PL-BS-MMs) was selected as the nanoscale carriers. The CCS-films containing Cu B loaded PL-SDC-MMs was evaluated for the mechanical properties, mucoadhesion properties, in vitro water-uptake, in vitro release and morphological properties, respectively. The optimal CCS-films containing Cu B loaded PL-SDC-MMs was easily reconstituted in a transparent and clear solution with spherical micelles in the submicron range. The in vivo study revealed a greater and more extended release of Cu B from nanoscale CCS-films compared to that from a conventional CCS films (C-CCS-films) and oral marketed tablet (Hulusupian). The absorption of Cu B from CCS-films containing Cu B loaded PL-SDC-MMs resulted in 2.69-fold increased in bioavailability as compared to conventional tablet formulation and 10.46 times with reference to the C-CCS-films formulation. Thus, this kind of mucoadhesive buccal film might be an alternative safe route for delivery of Cu B with better patient compliance and higher bioavailability for the treatments. PMID:24467528

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

    PubMed

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

    2015-07-01

    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. PMID:25899288

  18. 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. PMID:25033434

  19. 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. PMID:26295147

  20. 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. PMID:26820107

  1. Development and characterization of mucoadhesive chitosan films for ophthalmic delivery of cyclosporine A.

    PubMed

    Hermans, Kris; Van den Plas, Dave; Kerimova, Sabina; Carleer, Robert; Adriaensens, Peter; Weyenberg, Wim; Ludwig, Annick

    2014-09-10

    Ocular chitosan films were prepared in order to prolong ocular delivery of cyclosporine A. The mucoadhesive films were prepared using the solvent casting evaporation method. A 2(4) full factorial design was used to evaluate the effect of 4 preparation parameters on the film thickness, swelling index and mechanical properties. Moreover, uniformity of content and in vitro drug release were investigated. Possible interactions between the film excipients were studied by FTIR analysis. In vitro experiments were performed in order to evaluate the cytotoxicity and anti-inflammatory activity of the chitosan films. Film thickness, water uptake, mechanical properties and in vitro release of cyclosporine A were dependent on film composition, especially on the amount of plasticizer. Lower drug release was measured from chitosan films containing a higher amount of plasticizer as glycerol decreased the swelling of chitosan films. FTIR spectra suggest a reorganization of hydrogen bonds between chitosan chains in the presence of glycerol and cyclodextrins. None of the film formulations showed significant cytotoxicity as compared to the negative control using human epithelial cells (HaCaT). Cyclosporine A dispersed in the various film formulations remained anti-inflammatorily active as significant suppression of interleukin-2 secretion in concanavalin A stimulated Jurkat T cells was measured. PMID:24929014

  2. 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

  3. 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

  4. 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. PMID:25257714

  5. External Cross-linked Mucoadhesive Microbeads for Prolonged Drug Release: Development and In vitro Characterization

    PubMed Central

    Patel, Harshil; Srinatha, A.; Sridhar, B. K.

    2014-01-01

    Mucoadhesive microbeads of low methoxyl pectin were prepared, either alone or in combinations with hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose, methyl cellulose and carbopol 934P, by ionotropic gelation. The influence of copolymers on mucoadhesivity, microbeads characteristics and in vitro drug release was investigated. Spherical microbeads with 78.69±0.59 to 85.84±0.78% drug entrapment and of a size of 791.90±4.58 to 960.88±4.61 μm were prepared. The concentration of cross linking agent affects the encapsulation efficiency of microbeads. Mucoadhesiveness of microbeads was dependent on the concentration of copolymers. The formulations exhibiteda pH-dependent release and followed diffusion-controlled first-order kinetics. PMID:25425758

  6. 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

  7. 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

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

    PubMed

    Nur, M; Ramchandran, L; Vasiljevic, T

    2016-06-01

    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 -11.92mV). 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. PMID:27083363

  9. 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. PMID:26592698

  10. Polysaccharide-Based Micelles for Drug Delivery

    PubMed Central

    Zhang, Nan; Wardwell, Patricia R.; Bader, Rebecca A.

    2013-01-01

    Delivery of hydrophobic molecules and proteins has been an issue due to poor bioavailability following administration. Thus, micelle carrier systems are being investigated to improve drug solubility and stability. Due to problems with toxicity and immunogenicity, natural polysaccharides are being explored as substitutes for synthetic polymers in the development of new micelle systems. By grafting hydrophobic moieties to the polysaccharide backbone, self-assembled micelles can be readily formed in aqueous solution. Many polysaccharides also possess inherent bioactivity that can facilitate mucoadhesion, enhanced targeting of specific tissues, and a reduction in the inflammatory response. Furthermore, the hydrophilic nature of some polysaccharides can be exploited to enhance circulatory stability. This review will highlight the advantages of polysaccharide use in the development of drug delivery systems and will provide an overview of the polysaccharide-based micelles that have been developed to date. PMID:24300453

  11. 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. PMID:26563727

  12. Drug delivery systems.

    PubMed

    Robinson, D H; Mauger, J W

    1991-10-01

    New and emerging drug delivery systems for traditional drugs and the products of biotechnology are discussed, and the role of the pharmacist in ensuring the appropriate use of these systems is outlined. Advantages of advanced drug delivery systems over traditional systems are the ability to deliver a drug more selectively to a specific site; easier, more accurate, less frequent dosing; decreased variability in systemic drug concentrations; absorption that is more consistent with the site and mechanism of action; and reductions in toxic metabolites. Four basic strategies govern the mechanisms of advanced drug delivery: physical, chemical, biological, and mechanical. Oral drug delivery systems use natural and synthetic polymers to deliver the product to a specific region in the gastrointestinal tract in a timely manner that minimizes adverse effects and increases drug efficacy. Innovations in injectable and implantable delivery systems include emulsions, particulate delivery systems, micromolecular products and macromolecular drug adducts, and enzymatic-controlled delivery. Options for noninvasive drug delivery include the transdermal, respiratory, intranasal, ophthalmic, lymphatic, rectal, intravaginal, and intrauterine routes as well as topical application. Rapid growth is projected in the drug delivery systems market worldwide in the next five years. Genetic engineering has mandated the development of new strategies to deliver biotechnologically derived protein and peptide drugs and chemoimmunoconjugates. The role of the pharmacist in the era of advanced drug delivery systems will be broad based, including administering drugs, compounding, calculating dosages based on pharmacokinetic and pharmacodynamic monitoring, counseling, and research. The advent of advanced drug delivery systems offers pharmacists a new opportunity to assume an active role in patient care. PMID:1772110

  13. Nanotransporters for drug delivery.

    PubMed

    Lühmann, Tessa; Meinel, Lorenz

    2016-06-01

    Soluble nanotransporters for drugs can be profiled for targeted delivery particularly to maximize the efficacy of highly potent drugs while minimizing off target effects. This article outlines on the use of biological carrier molecules with a focus on albumin, various drug linkers for site specific release of the drug payload from the nanotransporter and strategies to combine these in various ways to meet different drug delivery demands particularly the optimization of the payload per nanotransporter. PMID:26773302

  14. Chitosan: a propitious biopolymer for drug delivery.

    PubMed

    Duttagupta, Dibyangana S; Jadhav, Varsha M; Kadam, Vilasrao J

    2015-01-01

    Scientists have always been interested in the use of natural polymers for drug delivery. Chitosan, being a natural cationic polysaccharide has received a great deal of attention in the past few years. It is obtained by deacetylation of chitin and is regarded as the second most ubiquitous polymer subsequent to cellulose on earth. Unlike other natural polymers, the cationic charge possessed by chitosan is accountable for imparting interesting physical and chemical properties. Chitosan has been widely exploited for its mucoadhesive character, permeation enhancing properties and controlled release of drugs. Moreover it's non-toxic, biocompatible and biodegradable properties make it a good candidate for novel drug delivery system. This review provides an insight on various chitosan based formulations for drug delivery. Some of the current applications of chitosan in areas like ophthalmic, nasal, buccal, sublingual, gastro-retentive, pulmonary, transdermal, colon-specific and vaginal drug delivery have been discussed. In addition, active targeting of drugs to tumor cells using chitosan has been described. Lastly a brief section covering the safety aspects of chitosan has also been reviewed. PMID:25761010

  15. 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. PMID:12944135

  16. 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. PMID:27173823

  17. Ocular drug delivery.

    PubMed

    Gaudana, Ripal; Ananthula, Hari Krishna; Parenky, Ashwin; Mitra, Ashim K

    2010-09-01

    Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases. PMID:20437123

  18. Transdermal drug delivery

    PubMed Central

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

  19. Zolpidem Mucoadhesive Formulations for Intranasal Delivery: Characterization, In Vitro Permeability, Pharmacokinetics, and Nasal Ciliotoxicity in Rats.

    PubMed

    Wang, Yanfeng; Li, Mi; Qian, Shuai; Zhang, Qizhi; Zhou, Limin; Zuo, Zhong; Lee, Benjamin; Toh, Melvin; Ho, Tony

    2016-09-01

    Zolpidem is a non-benzodiazepine hypnotic for the treatment of insomnia characterized by difficulties with sleep initiation. Our study aimed at developing a zolpidem mucoadhesive formulation with minimal local toxicity, prolonged nasal residence time, and enhanced absorption after intranasal delivery. In vitro permeability studies using artificial membrane and Calu-3 cell culture model indicated efficient permeability of zolpidem. Aqueous solubility of zolpidem was found to be significantly improved by hydroxypropyl-β-cyclodextrin. Various mucoadhesive formulations were then prepared comprising zolpidem, hydroxypropyl-β-cyclodextrin, and mucoadhesive polymers such as hydroxypropyl methylcellulose, sodium carboxymethylcellulose, and sodium alginate. Pharmacokinetic studies in rats demonstrated that intranasally administered zolpidem could achieve significantly faster absorption rate and higher plasma concentration than that from oral route. In comparison with solution formulation (ZLP-S03), the optimized mucoadhesive formulation (ZLP-B01) containing 0.25% hydroxypropyl methylcellulose was found to improve Cmax from 352.6 ± 86.0 to 555.7 ± 175.8 ng/mL, and AUC0-inf from 32,890 ± 7547 to 65,447 ± 36,996 ng·min/mL with mild nasal ciliotoxicity in rats. PMID:27189774

  20. 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

  1. Mucoadhesive properties of various pectins on gastrointestinal mucosa: an in vitro evaluation using texture analyzer.

    PubMed

    Thirawong, Nartaya; Nunthanid, Jurairat; Puttipipatkhachorn, Satit; Sriamornsak, Pornsak

    2007-08-01

    Mucoadhesive performance of various pectins with different degrees of esterification and molecular weights was examined with porcine gastrointestinal (GI) mucosa, i.e. buccal, stomach, small intestine and large intestine, using a texture analyzer equipped with mucoadhesive platform. The instrumental parameters and test conditions such as pre-hydration time of pectin disc, contact time, contact force, test speed of probe withdrawal, GI tissue and test medium were also studied. Two parameters derived from texture analysis, namely maximum detachment force (F(max)) and work of adhesion (W(ad)), were used as parameters for comparison of mucoadhesive performance. The results indicated that degree of hydration of pectin disc affected the mucoadhesive properties. The mucoadhesion of pectin increased with the increased contact time and contact force, but not by the increased probe withdrawal speed. Tissue from different parts of GI tract and test medium also influenced the mucoadhesion. Pectins showed a stronger mucoadhesion on large intestinal mucosa than on small intestinal mucosa. The mucoadhesive properties of pectins on gastric mucosa depended on pH of the medium; a higher F(max) and W(ad) in a pH 4.8 medium than a pH 1.2 medium was revealed. Additionally, pectin showed a significantly higher mucoadhesion than carbomer934P in most of the GI mucosa tested. The results also demonstrated that the mucoadhesive performance of pectins largely depended on their characteristics, i.e. higher degree of esterification and molecular weight gave a stronger mucoadhesion. These findings suggest that pectin can be used as a mucoadhesive carrier for GI-mucoadhesive drug delivery systems. PMID:17321731

  2. 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. PMID:25005586

  3. 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

  4. 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. PMID:25879307

  5. PECTIN IN CONTROLLED DRUG DELIVERY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Controlled drug delivery remains a research focus for public health to enhance patient compliance, drug efficiency and to reduce the side effects of drugs. Pectin, an edible plant polysaccharide, has shown potential for the construction of drug delivery systems for site-specific drug delivery. Sev...

  6. 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

  7. 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. PMID:26737259

  8. Nanotopography applications in drug delivery.

    PubMed

    Walsh, Laura A; Allen, Jessica L; Desai, Tejal A

    2015-01-01

    Refinement of micro- and nanofabrication in the semiconductor field has led to innovations in biomedical technologies. Nanotopography, in particular, shows great potential in facilitating drug delivery. The flexibility of fabrication techniques has created a diverse array of topographies that have been developed for drug delivery applications. Nanowires and nanostraws deliver drug cytosolically for in vitro and ex vivo applications. In vivo drug delivery is limited by the barrier function of the epithelium. Nanowires on microspheres increase adhesion and residence time for oral drug delivery, while also increasing permeability of the epithelium. Low aspect ratio nanocolumns increase paracellular permeability, and in conjunction with microneedles increase transdermal drug delivery of biologics in vivo. In summary, nanotopography is a versatile tool for drug delivery. It can deliver directly to cells or be used for in vivo delivery across epithelial barriers. This editorial highlights the application of nanotopography in the field of drug delivery. PMID:26512871

  9. Mucoadhesive microparticles for local treatment of gastrointestinal diseases.

    PubMed

    Preisig, Daniel; Roth, Roger; Tognola, Sandy; Varum, Felipe J O; Bravo, Roberto; Cetinkaya, Yalcin; Huwyler, Jörg; Puchkov, Maxim

    2016-08-01

    Mucoadhesive microparticles formulated in a capsule and delivered to the gastrointestinal tract might be useful for local drug delivery. However, swelling and agglomeration of hydrophilic polymers in the gastrointestinal milieu can have a negative influence on particle retention of mucoadhesive microparticles. In this work, we investigated the impact of dry-coating with nano-sized hydrophilic fumed silica on dispersibility and particle retention of mucoadhesive microparticles. As a model for local treatment of gastrointestinal diseases, antibiotic therapy of Clostridium difficile infections with metronidazole was selected. For particle preparation, we used a two-step fluidized-bed method based on drug loading of porous microcarriers and subsequent outer coating with the mucoadhesive polymer chitosan. The prepared microparticles were analysed for drug content, and further characterized by thermal analysis, X-ray diffraction, and scanning electron microscopy. The optimal molecular weight and content of chitosan were selected by measuring particle retention on porcine colonic mucosa under dynamic flow conditions. Mucoadhesive microparticles coated with 5% (weight of chitosan coating/total weight of particles) of low molecular weight chitosan showed good in vitro particle retention, and were used for the investigation of dispersibility enhancement. By increasing the amount of silica, the dissolution rate measured in the USPIV apparatus was increased, which was an indirect indication for improved dispersibility due to increased surface area. Importantly, mucoadhesion was not impaired up to a silica concentration of 5% (w/w). In summary, mucoadhesive microparticles with sustained-release characteristics over several hours were manufactured at pilot scale, and dry-coating with silica nanoparticles has shown to improve the dispersibility, which is essential for better particle distribution along the intestinal mucosa in humans. Therefore, this advanced drug delivery

  10. Ex-vivoand in-vitro assessment of mucoadhesive patches containing the gel-forming polysaccharide psyllium for buccal delivery of chlorhexidine base.

    PubMed

    Cavallari, Cristina; Brigidi, Patrizia; Fini, Adamo

    2015-12-30

    The aim of the present study was to evaluate the gel-forming polysaccharide psyllium in the preparation of mucoadhesive patches for the controlled release of chlorhexidine (CHX) to treat pathologies in the oral cavity, using the casting-solvent evaporation technique. A number of different film-forming semi-synthetic polymers, such as sodium carboxymethyl cellulose (SCMC) and hydroxypropylmethyl cellulose (HPMC) were evaluated for comparison. The patch formulations were characterized in terms of drug content, morphology surface, swelling and mucoadhesive properties, microbiology inhibition assay and in vitro release tests. Three ex-vivo testswere carried out using porcine mucosa: an alternative dissolution test using artificial saliva that allows contemporary measurement of dissolution and mucoadhesion, a permeation test through the mucosa and the measurement of mucoadhesion using a Nouy tensile tester, as the maximum force required for the separation of the patch from the mucosa surface. The patches were also examined for determination of the minimum inhibitory concentration in cultures of Escherichia coli and Staphylococcus aureus. All the patches incorporating psyllium were found suitable in terms of external morphology, mucoadhesion and controlled release of the drug: in the presence of psyllium the drug displays prolonged zero-order release related to slower swelling rate of the system. PMID:26541304

  11. 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. PMID:24471787

  12. 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.

  13. Drug delivery strategies for the treatment of Helicobacter pylori infections.

    PubMed

    Conway, B R

    2005-01-01

    Helicobacter pylori is one of the most common pathogenic bacterial infections, colonising an estimated half of all humans. It is associated with the development of serious gastroduodenal disease - including peptic ulcers, gastric lymphoma and acute chronic gastritis. Current recommended regimes are not wholly effective and patient compliance, side-effects and bacterial resistance can be problematic. Drug delivery to the site of residence in the gastric mucosa may improve efficacy of the current and emerging treatments. Gastric retentive delivery systems potentially allow increased penetration of the mucus layer and therefore increased drug concentration at the site of action. Proposed gastric retentive systems for the enhancement of local drug delivery include floating systems, expandable or swellable systems and bioadhesive systems. Generally, problems with these formulations are lack of specificity, limited to mucus turnover or failure to persist in the stomach. Gastric mucoadhesive systems are hailed as a promising technology to address this issue, penetrating the mucus layer and prolonging activity at the mucus-epithelial interface. This review appraises gastroretentive delivery strategies specifically with regard to their application as a delivery system to target Helicobacter. As drug-resistant strains emerge, the development of a vaccine to eradicate and prevent reinfection is an attractive proposition. Proposed prophylactic and therapeutic vaccines have been delivered using a number of mucosal routes using viral and non-viral vectors. The delivery form, inclusion of adjuvants, and delivery regime will influence the immune response generated. PMID:15777232

  14. Study of the Mucoadhesive Potential of Carbopol Polymer in the Preparation of Microbeads Containing the Antidiabetic Drug Glipizide.

    PubMed

    Bera, Khokan; Mazumder, Bhaskar; Khanam, Jasmina

    2016-06-01

    The present investigation was aimed at exploitation of the mucoadhesive potential of carbopol 934P polymer in developing microbeads of glipizide (GLP) for its effectivity in controlling blood sugar in diabetic patients. Various batches of GLP beads were prepared by an emulsion-solvent evaporation technique using the release-retarding polymer carbopol and subjected to a systematic evaluation such as physical characterization, ex vivo mucoadhesion, hydration and erosion test, and in vitro drug release; and instrumental and in vivo studies were performed with the best formulation. The highest yield and loading efficiency were observed as 94 and ∼90%, respectively. The mean particle size of the microbeads ranged from 832 to 742 μm. The oval shape of the microbeads with slight roughness was apparent in the SEM micrograph. The release period was extended till 18 h. In vitro release of the drug from the beads followed the diffusion and erosion mechanism. In the oral glucose tolerance test (OGTT), there is a significant (p < 0.01) reduction in fasting blood glucose levels in Wistar rat and guinea pig in comparison with that using the marketed product. Results indicated that process parameters-drug-polymer ratio, concentration of the surfactant, and stirring speed-controlled the various characteristics of the microparticles. The mucoadhesivity test ensured strong adherence of the beads to the mucosal membrane in pH 1.2 for a prolonged period. Owing to the mucoadhesivity of carbopol 934P, prolonged release of GLP and reduction of fasting sugar in the animal model were observed to a satisfactory level, and thus, management of diabetes in a better manner is expected with this new formulation. PMID:26335417

  15. MEMS: Enabled Drug Delivery Systems.

    PubMed

    Cobo, Angelica; Sheybani, Roya; Meng, Ellis

    2015-05-01

    Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed. PMID:25703045

  16. 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. PMID:25036601

  17. Development of mucoadhesive sprayable gellan gum fluid gels.

    PubMed

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

    2015-07-01

    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. PMID:25863119

  18. 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

  19. Transdermal delivery of propranolol hydrochloride through chitosan nanoparticles dispersed in mucoadhesive gel.

    PubMed

    Al-Kassas, Raida; Wen, Jingyuan; Cheng, Angel En-Miao; Kim, Amy Moon-Jung; Liu, Stephanie Sze Mei; Yu, Joohee

    2016-11-20

    This study aimed at improving the systemic bioavailability of propranolol-HCl by the design of transdermal drug delivery system based on chitosan nanoparticles dispersed into gels. Chitosan nanoparticles were prepared by ionic gelation technique using tripolyphosphate (TPP) as a cross-linking agent. Characterization of the nanoparticles was focused on particle size, zeta potential, surface texture and morphology, and drug encapsulation efficiency. The prepared freeze dried chitosan nanoparticles were dispersed into gels made of poloxamer and carbopol and the rheological behaviour and the adhesiveness of the gels were investigated. The results showed that smallest propranolol loaded chitosan nanoparticles were achieved with 0.2% chitosan and 0.05% TPP. Nanoparticles were stable in suspension with a zeta potential (ZP) above ±30mV to prevent aggregation of the colloid. Zeta potential was found to increase with increasing chitosan concentration due to its cationic nature. At least 70% of entrapment efficiency and drug loading were achieved for all prepared nanoparticles. When chitosan nanoparticles dispersed into gel consisting of poloxamer and carbopol, the resultant formulation exhibited thixotropic behaviour with a prolonged drug release properties as shown by the permeation studies through pig ear skin. Our study demonstrated that the designed nanoparticles-gel transdermal delivery system has a potential to improve the systemic bioavailability and the therapeutic efficacy of propranolol-HCl. PMID:27561485

  20. 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

  1. 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. PMID:25598798

  2. 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

  3. 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

  4. Hollow pollen shells to enhance drug delivery.

    PubMed

    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

  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. 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. PMID:27196368

  7. 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. PMID:24144200

  8. Polymer Particulates in Drug Delivery.

    PubMed

    Kaur, Harmeet; Kumar, Virender; Kumar, Krishan; Rathor, Sandeep; Kumari, Parveen; Singh, Jasbir

    2016-01-01

    Development of effective drug delivery systems is important for medicine and healthcare. Polymer particulates (micro- and nanoparticles) have opened new opportunities in the field of drug delivery by overcoming various limitations of conventional delivery methods. The properties of polymeric particles can be readily tuned by precisely engineering the constituent blocks of polymers for improving drug loading, release rate, pharmacokinetics, targeting, etc. The end-groups of various polymers can be readily modified with ligands making them suitable for recognizing by cell-specific receptors, providing cellular specificity, and superior intracellular delivery. This review will mainly cover delivery of many potential drugs and biomolecules by means of polymeric microparticles, nanoparticles and copolymer micelles or assemblies. An overview about formulation methods of polymer particulates has also been addressed. Attempt has been made to cover all the potential polymers that are well known in pharmaceutical history. PMID:26898740

  9. Osmotic micropumps for drug delivery.

    PubMed

    Herrlich, Simon; Spieth, Sven; Messner, Stephan; Zengerle, Roland

    2012-11-01

    This paper reviews miniaturized drug delivery systems applying osmotic principles for pumping. Osmotic micropumps require no electrical energy and consequently enable drug delivery systems of smallest size for a broad field of new applications. In contrast to common tablets, these pumps provide constant (zero-order) drug release rates. This facilitates systems for long term use not limited by gastrointestinal transit time and first-pass metabolism. The review focuses on parenteral routes of administration targeting drug delivery either in a site-specific or systemic way. Osmotic pumps consist of three building blocks: osmotic agent, solvent, and drug. This is used to categorize pumps into (i) single compartment systems using water from body fluids as solvent and the drug itself as the osmotic agent, (ii) two compartment systems employing a separate osmotic agent, and (iii) multi-compartment architectures employing solvent, drug and osmotic agent separately. In parallel to the micropumps, relevant applications and therapies are discussed. PMID:22370615

  10. Bioresponsive matrices in drug delivery

    PubMed Central

    2010-01-01

    For years, the field of drug delivery has focused on (1) controlling the release of a therapeutic and (2) targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drug delivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drug delivery vehicles. This review describes the most recent advances in "smart" drug delivery systems that respond to one or multiple stimuli. PMID:21114841

  11. 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

  12. A novel in situ gel for sustained drug delivery and targeting.

    PubMed

    Ganguly, Sudipta; Dash, Alekha K

    2004-05-19

    The objective of this study was to develop a novel chitosan-glyceryl monooleate (GMO) in situ gel system for sustained drug delivery and targeting. The delivery system consisted of 3% (w/v) chitosan and 3% (w/v) GMO in 0.33M citric acid. In situ gel was formed at a biological pH. In vitro release studies were conducted in Sorensen's phosphate buffer (pH 7.4) and drugs were analyzed either by HPLC or spectrophotometry. Characterization of the gel included the effect of cross-linker, determination of diffusion coefficient and water uptake by thermogravimetric analysis (TGA). Mucoadhesive property of the gel was evaluated in vitro using an EZ-Tester. Incorporation of a cross-linker (glutaraldehyde) retarded the rate and extent of drug release. The in vitro release can further be sustained by replacing the free drug with drug-encapsulated microspheres. Drug release from the gel followed a matrix diffusion controlled mechanism. Inclusion of GMO enhanced the mucoadhesive property of chitosan by three- to sevenfold. This novel in situ gel system can be useful in the sustained delivery of drugs via oral as well as parenteral routes. PMID:15113617

  13. 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

  14. 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

  15. Development of low methoxy amidated pectin-based mucoadhesive patches for buccal delivery of triclosan: effect of cyclodextrin complexation.

    PubMed

    Jug, Mario; Kosalec, Ivan; Maestrelli, Francesca; Mura, Paola

    2012-11-01

    A novel mucoadhesive buccal patch formulation of triclosan (TR), a broad spectrum antibacterial agent, was developed using low methoxy amidated pectin (AMP). The integrity of AMP matrix was improved by addition of 20% (w/w) Carbopol (CAR). The efficiency of β-cyclodextrin-epichlorohydrin polymer (EPIβCD) and anionic carboxymethylated β-cyclodextrin-epichlorohydrin polymer (CMEPIβCD) in optimization of TR solubility and release from such a matrix was investigated and confronted to that of parent β-cyclodextrin (βCD). Loading of TR/βCD co-ground complex into AMP/CAR matrix resulted in a biphasic release profile which was sensitive upon the hydration degree of the matrix, due to lower solubilizing efficiency of βCD, while the drug release from patches loaded with TR/EPIβCD complex was significantly faster with a constant release rate. Microbiological studies evidenced faster onset and more pronounced antibacterial action of TR/EPIβCD loaded patches, clearly demonstrating their good therapeutic potential in eradication of Streptococcus mutans, a cariogenic bacteria, from the oral cavity. PMID:22944449

  16. 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

  17. 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

  18. 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. PMID:24818769

  19. Preparation and characterization of a novel pH-sensitive coated microsphere for duodenum-specific drug delivery.

    PubMed

    Zhou, Dan; Zhu, Xi; Wang, Yang; Jin, Yun; Xu, Xuefan; Fan, Tingting; Liu, Yan; Zhang, Zhirong; Huang, Yuan

    2012-05-01

    The aim of this study is to develop a duodenum-specific drug delivery system on the basis of a pH-sensitive coating and a mucoadhesive inner core for eradication of Helicobacter pylori (H. pylori) in the ulcer duodenum. Hydroxypropyl methylcellulose acetate maleate (HPMCAM) was used as the pH-sensitive material, which dissolves around pH 3.0. The mucoadhesive microspheres loaded with furazolidone (FZD-ad-MS) were prepared by the emulsification-solvent evaporation method using Carbopol 971NP as the mucoadhesive polymer. The prepared pH-sensitive coated mucoadhesive microspheres (AM-coated-MS) were characterized in regards to particle size, drug loading efficiency, morphological change, drug stability, drug release and in vitro anti-H. pylori activity. The particle size was 160.97 ± 47.24 μm and 336.44 ± 129.34 μm, and the drug content was 42.33 ± 3.43% and 10.96 ± 1.29% for FZD-ad-MS and AM-coated-MS, respectively. The morphological changes in different pH media were characterized by scanning electron microscopy (SEM). HPMCAM coating improved the stability of the FZD-ad-MS and these particles were expected to remain intact until their arrival in the duodenum. The drug release was extremely suppressed at pH 1.2 for AM-coated-MS, but increased at pH 4.0 after regeneration of FZD-ad-MS. In addition, FZD-ad-MS exhibited excellent anti-H. pylori activity in vitro. Thus, the HPMCAM-coated microspheres developed in this study hold great promise for use as a duodenum-specific drug delivery system for H. pylori clearance. PMID:22644851

  20. 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. PMID:26502109

  1. 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). PMID:26333938

  2. 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

  3. 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. PMID:25336429

  4. 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

  5. Nanostructures for protein drug delivery.

    PubMed

    Pachioni-Vasconcelos, Juliana de Almeida; Lopes, André Moreni; Apolinário, Alexsandra Conceição; Valenzuela-Oses, Johanna Karina; Costa, Juliana Souza Ribeiro; Nascimento, Laura de Oliveira; Pessoa, Adalberto; Barbosa, Leandro Ramos Souza; Rangel-Yagui, Carlota de Oliveira

    2016-02-01

    Use of nanoscale devices as carriers for drugs and imaging agents has been extensively investigated and successful examples can already be found in therapy. In parallel, recombinant DNA technology together with molecular biology has opened up numerous possibilities for the large-scale production of many proteins of pharmaceutical interest, reflecting in the exponentially growing number of drugs of biotechnological origin. When we consider protein drugs, however, there are specific criteria to take into account to select adequate nanostructured systems as drug carriers. In this review, we highlight the main features, advantages, drawbacks and recent developments of nanostructures for protein encapsulation, such as nanoemulsions, liposomes, polymersomes, single-protein nanocapsules and hydrogel nanoparticles. We also discuss the importance of nanoparticle stabilization, as well as future opportunities and challenges in nanostructures for protein drug delivery. PMID:26580477

  6. 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.

  7. 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.

  8. Gellan gum microspheres crosslinked with trivalent ion: effect of polymer and crosslinker concentrations on drug release and mucoadhesive properties.

    PubMed

    Boni, Fernanda Isadora; Prezotti, Fabíola Garavello; Cury, Beatriz Stringhetti Ferreira

    2016-08-01

    Gellan gum microspheres were obtained by ionotropic gelation technique, using the trivalent ion Al(3+). The percentage of entrapment efficiency ranged from 48.76 to 87.52% and 2(2) randomized full factorial design demonstrated that both the increase of polymer concentration and the decrease of crosslinker concentration presented a positive effect in the amount of encapsulated drug. Microspheres size and circularity ranged from 700.17 to 938.32 μm and from 0.641 to 0.796 μm, respectively. The increase of polymer concentration (1-2%) and crosslinker concentration (3-5%) led to the enlargement of particle size and circularity. However, the association of increased crosslinker concentration and reduced polymer content made the particles more irregular. In vitro and ex vivo tests evidenced the high mucoadhesiveness of microspheres. The high liquid uptake ability of the microspheres was demonstrated and the pH variation did not affect this parameter. Drug release was pH dependent, with low release rates in acid pH (42.40% and 44.93%) and a burst effect in phosphate buffer pH (7.4). The Weibull model had the best correlation with the drug release data, demonstrating that the release process was driven by a complex mechanism involving the erosion and swelling of the matrix or by non-Fickian diffusion. PMID:26616390

  9. Nanothermodynamics mediates drug delivery.

    PubMed

    Stefi, Aikaterina L; Sarantopoulou, Evangelia; Kollia, Zoe; Spyropoulos-Antonakakis, Nikolaos; Bourkoula, Athanasia; Petrou, Panagiota S; Kakabakos, Sotirios; Soras, Georgios; Trohopoulos, Panagiotis N; Nizamutdinov, Alexey S; Semashko, Vadim V; Cefalas, Alkiviadis Constantinos

    2015-01-01

    The efficiency of penetration of nanodrugs through cell membranes imposes further complexity due to nanothermodynamic and entropic potentials at interfaces. Action of nanodrugs is effective after cell membrane penetration. Contrary to diffusion of water diluted common molecular drugs, nanosize imposes an increasing transport complexity at boundaries and interfaces (e.g., cell membrane). Indeed, tiny dimensional systems brought the concept of "nanothermodynamic potential," which is proportional to the number of nanoentities in a macroscopic system, from either the presence of surface and edge effects at the boundaries of nanoentities or the restriction of the translational and rotational degrees of freedom of molecules within them. The core element of nanothermodynamic theory is based on the assumption that the contribution of a nanosize ensemble to the free energy of a macroscopic system has its origin at the excess interaction energy between the nanostructured entities. As the size of a system is increasing, the contribution of the nanothermodynamic potential to the free energy of the system becomes negligible. Furthermore, concentration gradients at boundaries, morphological distribution of nanoentities, and restriction of the translational motion from trapping sites are the source of strong entropic potentials at the interfaces. It is evident therefore that nanothermodynamic and entropic potentials either prevent or allow enhanced concentration very close to interfaces and thus strongly modulate nanoparticle penetration within the intracellular region. In this work, it is shown that nano-sized polynuclear iron (III)-hydroxide in sucrose nanoparticles have a nonuniform concentration around the cell membrane of macrophages in vivo, compared to uniform concentration at hydrophobic prototype surfaces. The difference is attributed to the presence of entropic and nanothermodynamic potentials at interfaces. PMID:25416996

  10. 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

  11. 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

  12. 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.

  13. Peptide and protein delivery using new drug delivery systems.

    PubMed

    Jain, Ashish; Jain, Aviral; Gulbake, Arvind; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K

    2013-01-01

    Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery. PMID:23662604

  14. 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

  15. 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. PMID:24291123

  16. Opportunities in respiratory drug delivery.

    PubMed

    Pritchard, John N; Giles, Rachael D

    2014-12-01

    A wide range of asthma and chronic obstructive pulmonary disease products are soon to be released onto the inhaled therapies market and differentiation between these devices will help them to gain market share over their competitors. Current legislation is directing healthcare towards being more efficient and cost-effective in order to continually provide quality care despite the challenges of aging populations and fewer resources. Devices and drugs that can be differentiated by producing improved patient outcomes would, therefore, be likely to win market share. In this perspective article, the current and potential opportunities for the successful delivery and differentiation of new inhaled drug products are discussed. PMID:25531928

  17. Nasal drug delivery in humans.

    PubMed

    Bitter, Christoph; Suter-Zimmermann, Katja; Surber, Christian

    2011-01-01

    Intranasal administration is an attractive option for local and systemic delivery of many therapeutic agents. The nasal mucosa is--compared to other mucosae--easily accessible. Intranasal drug administration is noninvasive, essentially painless and particularly suited for children. Application can be performed easily by patients or by physicians in emergency settings. Intranasal drug delivery offers a rapid onset of therapeutic effects (local or systemic). Nasal application circumvents gastrointestinal degradation and hepatic first-pass metabolism of the drug. The drug, the vehicle and the application device form an undividable triad. Its selection is therefore essential for the successful development of effective nasal products. This paper discusses the feasibility and potential of intranasal administration. A series of questions regarding (a) the intended use (therapeutic considerations), (b) the drug, (c) the vehicle and (d) the application device (pharmaceutical considerations) are addressed with a view to their impact on the development of products for nasal application. Current and future trends and perspectives are discussed. PMID:21325837

  18. 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

  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. 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

  1. Carrier Deformability in Drug Delivery.

    PubMed

    Morilla, Maria Jose; Romero, Eder Lilia

    2016-01-01

    Deformability is a key property of drug carriers used to increase the mass penetration across the skin without disrupting the lipid barrier. Highly deformable vesicles proved to be more effective than conventional liposomes in delivering drugs into and across the mammalian skin upon topical non occlusive application. In the past five years, highly deformable vesicles have been used for local delivery of drugs on joint diseases, skin cancer, atopic dermatitis, would healing, psoriasis, scar treatment, fungal, bacteria and protozoa infections. Promising topical vaccination strategies rely also in this type of carriers. Here we provide an overview on the main structural and mechanical features of deformable vesicles, to finish with an extensive update on their latest preclinical applications. PMID:26675226

  2. Development and characterisation of thermo reversible mucoadhesive moxifloxacin hydrochloride in situ ophthalmic gel

    PubMed Central

    Dholakia, M.; Thakkar, V.; Patel, N.; Gandhi, T.

    2012-01-01

    A sustain release thermo reversible in situ gel of Moxifloxacin Hydrochloride using mucoadhesive polymer was prepared. Mucoadhesive polymer was used to obtain an ophthalmic delivery system with improved mechanical and mucoadhesive properties that will provide prolong retention time for treatment of ocular diseases. Developed formulations were evaluated for drug-excipient compatibility study, pH, Clarity, Gelation temperature study, Mucoadhesion properties and in-vitro release studies. Drug-excipient compatibility study was performed by FTIR technique. The individual IR spectra of the pure drug and polymers as well as the combination spectra of the drug and polymer were taken, which indicate no interaction between Moxifloxacin and polymers when compared with infrared spectrum of pure drug as all functional group frequencies were present. The values of other parameters obtained were in acceptable range. In vitro release tests revealed that 98% drug was released from the in situ gel containing 0.5% and 1.00% HPMC in 12 hr. provides prolonged release. PMID:23066202

  3. 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. PMID:26501994

  4. Effect of non-cross-linked calcium on characteristics, swelling behaviour, drug release and mucoadhesiveness of calcium alginate beads.

    PubMed

    Dalaty, Adnan Al; Karam, Ayman; Najlah, Mohammad; Alany, Raid G; Khoder, Mouhamad

    2016-04-20

    In this study, ibuprofen-loaded calcium alginate beads (CABs) with varying amounts of non-cross-linked calcium (NCL-Ca) were prepared using different washing methods. The influence of NCL-Ca on beads properties was investigated. Increasing the number or duration of washes led to significant decreases in the amount of NCL-Ca whereas the impact of the volume of washes was not significant. Approximately 70% of the initial amount of Ca(2+) was NCL-Ca which was removable by washing while only 30% was cross-linked (CL-Ca). Ca(2+) release from the CABs was bimodal; NCL-Ca was burst-released followed by a slower release of CL-Ca. Washing methods and the amount of NCL-Ca had significant influences on the encapsulation efficiency, beads weight, beads swelling, drug release profile and the mucoadhesiveness of CABs. This study highlighted the importance of washing methods and the amount of NCL-Ca to establish CABs properties and understand their behaviour in the simulated intestinal fluids (SIFs). PMID:26876840

  5. 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

  6. Molecular aptamers for drug delivery.

    PubMed

    Tan, Weihong; Wang, Hui; Chen, Yan; Zhang, Xiaobing; Zhu, Haizhen; Yang, Chaoyong; Yang, Ronghua; Liu, Chen

    2011-12-01

    The active targeting of drugs in a cell-, tissue- or disease-specific manner represents a potentially powerful technology with widespread applications in medicine, including the treatment of cancers. Aptamers have properties such as high affinity and specificity for targets, easy chemical synthesis and modification, and rapid tissue penetration. They have become attractive molecules in diagnostics and therapeutics rivaling and, in some cases, surpassing other molecular probes, such as antibodies. In this review, we highlight the recent progress in aptamer-mediated delivery for therapeutics and disease-targeting based on aptamer integration with a variety of nanomaterials, such as gold nanorods, DNA micelles, DNA hydrogels and carbon nanotubes. PMID:21821299

  7. Carboxymethyl starch mucoadhesive microspheres as gastroretentive dosage form.

    PubMed

    Lemieux, Marc; Gosselin, Patrick; Mateescu, Mircea Alexandru

    2015-12-30

    Carboxymethyl starch microspheres (CMS-MS) were produced from carboxymethyl starch powder (CMS-P) with a degree of substitution (DS) from 0.1 to 1.5 in order to investigate the influence of DS on physicochemical, drug release and mucoadhesion properties as well as interactions with gastrointestinal tract (GIT) epithelial barrier models. Placebo and furosemide loaded CMS-MS were obtained by emulsion-crosslinking with sodium trimetaphosphate (STMP). DS had an impact on increasing equilibrium water uptake and modulating drug release properties of the CMS-MS according to the surrounding pH. The transepithelial electrical resistance (TEER) of NCI-N87 gastric cell monolayers was not influenced in presence of CMS-MS, whereas that of Caco-2 intestinal cell monolayers decreased with increasing DS but recovered initial values at about 15h post-treatment. CMS-MS with increasing DS also enhanced furosemide permeability across both NCI-N87 and Caco-2 monolayers at pH gradients from 3.0 to 7.4. Mucoadhesion of CMS-MS on gastric mucosa (acidic condition) increased with the DS up to 55% for a DS of 1.0 but decreased on neutral intestinal mucosa to less than 10% with DS of 0.1. The drug release, permeability enhancement and mucoadhesive properties of the CMS-MS suggest CMS-MS with DS between 0.6 and 1.0 as suitable excipient for gastroretentive oral delivery dosage forms. PMID:26456246

  8. Phospholipid-chitosan hybrid nanoliposomes promoting cell entry for drug delivery against cervical cancer.

    PubMed

    Saesoo, Somsak; Bunthot, Suphawadee; Sajomsang, Warayuth; Gonil, Pattarapond; Phunpee, Sarunya; Songkhum, Patsaya; Laohhasurayotin, Kritapas; Wutikhun, Tuksadon; Yata, Teerapong; Ruktanonchai, Uracha Rungsardthong; Saengkrit, Nattika

    2016-10-15

    This study emphasizes the development of a novel surface modified liposome as an anticancer drug nanocarrier. Quaternized N,O-oleoyl chitosan (QCS) was synthesized and incorporated into liposome vesicles, generating QCS-liposomes (Lip-QCS). The Lip-QCS liposomes were spherical in shape (average size diameter 171.5±0.8nm), with a narrow size distribution (PDI 0.1±0.0) and zeta potential of 11.7±0.7mV. In vitro mucoadhesive tests indicated that Lip-QCS possesses a mucoadhesive property. Moreover, the presence of QCS was able to induce the cationic charge on the surface of liposome. Cellular internalization of Lip-QCS was monitored over time, with the results revealing that the cell entry level of Lip-QCS was elevated at 24h. Following this, Lip-QCS were then employed to load cisplatin, a common platinum-containing anti-cancer drug, with a loading efficiency of 27.45±0.78% being obtained. The therapeutic potency of the loaded Lip-QCS was investigated using a 3D spheroid cervical cancer model (SiHa) which highlighted their cytotoxicity and apoptosis effect, and suitability as a controllable system for sustained drug release. This approach has the potential to assist in development of an effective drug delivery system against cervical cancer. PMID:27442151

  9. Fibrin Glue as a Drug Delivery System

    PubMed Central

    Spicer, Patrick P.; Mikos, Antonios G.

    2010-01-01

    Fibrin glue has been used surgically for decades for hemostasis as well as a sealant. It has also been researched as both a gel for cell delivery and a vehicle for drug delivery. The drug delivery applications for fibrin glue span tissue engineering to chemotherapy and involve several mechanisms for drug matrix interactions and control of release kinetics. Additionally, drugs or factors can be loaded in the gel via impregnation and tethering to the gel through covalent linkages or affinity based systems. This review highlights recent research of fibrin glue as a drug delivery vehicle. PMID:20637815

  10. 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. PMID:22149347

  11. 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

  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. PMID:24825492

  13. Physically facilitating drug-delivery systems

    PubMed Central

    Rodriguez-Devora, Jorge I; Ambure, Sunny; Shi, Zhi-Dong; Yuan, Yuyu; Sun, Wei; Xu, Tao

    2012-01-01

    Facilitated/modulated drug-delivery systems have emerged as a possible solution for delivery of drugs of interest to pre-allocated sites at predetermined doses for predefined periods of time. Over the past decade, the use of different physical methods and mechanisms to mediate drug release and delivery has grown significantly. This emerging area of research has important implications for development of new therapeutic drugs for efficient treatments. This review aims to introduce and describe different modalities of physically facilitating drug-delivery systems that are currently in use for cancer and other diseases therapy. In particular, delivery methods based on ultrasound, electrical, magnetic and photo modulations are highlighted. Current uses and areas of improvement for these different physically facilitating drug-delivery systems are discussed. Furthermore, the main advantages and drawbacks of these technologies reviewed are compared. The review ends with a speculative viewpoint of how research is expected to evolve in the upcoming years. PMID:22485192

  14. 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. PMID:24325540

  15. Polymers for Colon Targeted Drug Delivery

    PubMed Central

    Rajpurohit, H.; Sharma, P.; Sharma, S.; Bhandari, A.

    2010-01-01

    The colon targeted drug delivery has a number of important implications in the field of pharmacotherapy. Oral colon targeted drug delivery systems have recently gained importance for delivering a variety of therapeutic agents for both local and systemic administration. Targeting of drugs to the colon via oral administration protect the drug from degradation or release in the stomach and small intestine. It also ensures abrupt or controlled release of the drug in the proximal colon. Various drug delivery systems have been designed that deliver the drug quantitatively to the colon and then trigger the release of drug. This review will cover different types of polymers which can be used in formulation of colon targeted drug delivery systems. PMID:21969739

  16. 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. PMID:26353470

  17. 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

  18. 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

  19. Ispaghula mucilage-gellan mucoadhesive beads of metformin HCl: development by response surface methodology.

    PubMed

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

    2014-07-17

    Response surface methodology based on 3(2) factorial design was used to develop ispaghula (Plantago ovata F.) husk mucilage (IHM)-gellan gum (GG) mucoadhesive beads containing metformin HCl through Ca(2+)-ion cross-linked ionotropic-gelation technique for the use in oral drug delivery. GG to IHM ratio and cross-linker (CaCl2) concentration were investigated as independent variables. Drug encapsulation efficiency (DEE, %) and cumulative drug release after 10h (R10h, %) were analyzed as dependent variables. The optimized mucoadhesive beads (F-O) showed DEE of 94.24 ± 4.18%, R10h of 59.13 ± 2.27%. These beads were also characterized by SEM and FTIR analyses. The in vitro drug release from these beads showed controlled-release (zero-order) pattern with super case-II transport mechanism over 10h. The optimized beads showed pH-dependent swelling and good mucoadhesivity with the goat intestinal mucosa. The optimized IHM-GG mucoadhesive beads containing metformin HCl exhibited significant antidiabetic effect in alloxan-induced diabetic rats over 10h. PMID:24702916

  20. 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

  1. 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. PMID:27433574

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

    PubMed

    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

  3. 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

  4. Molecular aptamers for drug delivery

    PubMed Central

    Tan, Weihong; Wang, Hui; Chen, Yan; Zhang, Xiaobing; Zhu, Haizhen; Yang, Chaoyong; Yang, Ronghua

    2011-01-01

    The active targeting of drugs in a cell-, tissue-, or disease-specific manner represents a potentially powerful technology with widespread applications in medicine, including the treatment of cancers. Aptamers, with properties such as high affinity and specificity to their targets, easy chemical synthesis and modification, as well as rapid tissue penetration, have become attractive molecules in diagnostics and therapeutics. They rival and, in some cases, surpass other molecular probes, such as antibodies. In this review, we highlight the recent progress in aptamer-mediated delivery for therapeutics and disease-targeting based on aptamer integration with a variety of nanomaterials, such as gold nanorods, DNA-micelles, DNA-hydrogels and carbon nanotubes. PMID:21821299

  5. 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

  6. Targeted Drug Delivery in Pancreatic Cancer

    PubMed Central

    Yu, Xianjun; Zhang, Yuqing; Chen, Changyi; Yao, Qizhi; Li, Min

    2009-01-01

    Effective drug delivery in pancreatic cancer treatment remains a major challenge. Because of the high resistance to chemo and radiation therapy, the overall survival rate for pancreatic cancer is extremely low. Recent advances in drug delivery systems hold great promise for improving cancer therapy. Using liposomes, nanoparticles, and carbon nanotubes to deliver cancer drugs and other therapeutic agents such as siRNA, suicide gene, oncolytic virus, small molecule inhibitor and antibody has been a success in recent pre-clinical trials. However, how to improve the specificity and stability of the delivered drug using ligand or antibody directed delivery represent a major problem. Therefore, developing novel, specific, tumor-targeted drug delivery systems is urgently needed for this terrible disease. This review summarizes the current progress on targeted drug delivery in pancreatic cancer, and provides important information on potential therapeutic targets for pancreatic cancer treatment. PMID:19853645

  7. 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. PMID:25006687

  8. 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.

  9. Ocular Drug Delivery - New Strategies for Targeting Anterior and Posterior Segments of the Eye.

    PubMed

    Fangueiro, Joana F; Veiga, Francisco; Silva, Amelia M; Souto, Eliana B

    2016-01-01

    The ocular delivery of drugs encounters several limitations because of the dynamic and static barriers of the human's eye anatomy and physiology. The poor bioavailability of drugs are mainly related to the topical administration, i.e. eye drops which is the most common drug dosage form for the treatment of eye pathologies. Precorneal factors and drug limitations related to its solubility and susceptibility for physicochemical degradation could be the main reasons for the poor permeation and uptake in the ocular mucosa. Pathologies affecting the anterior and posterior segment of the eye are thereafter difficult to be treated and, given the chronic and degenerative nature of some of these injuries, it is crucial to improve drugs therapeutic effect. Nanotechnology-based delivery systems could be a suitable approach to overcome these limitations. Some of the most important colloidal systems are highlighted in this review, such as the use of mucoadhesive polymers, prodrugs, nanogels, liposomes, microemulsions, lipid and polymeric nanoparticles, cyclodextrins, dendrimers and nanocrystals, along with their clinical and therapeutic relevance for the administration of drugs for ocular delivery. PMID:26675225

  10. Recent advances in ocular drug delivery.

    PubMed

    Achouri, Djamila; Alhanout, Kamel; Piccerelle, Philippe; Andrieu, Véronique

    2013-11-01

    Amongst the various routes of drug delivery, the field of ocular drug delivery is one of the most interesting and challenging endeavors facing the pharmaceutical scientist. Recent research has focused on the characteristic advantages and limitations of the various drug delivery systems, and further research will be required before the ideal system can be developed. Administration of drugs to the ocular region with conventional delivery systems leads to short contact time of the formulations on the epithelium and fast elimination of drugs. This transient residence time involves poor bioavailability of drugs which can be explained by the tear production, non-productive absorption and impermeability of corneal epithelium. Anatomy of the eye is shortly presented and is connected with ophthalmic delivery and bioavailability of drugs. In the present update on ocular dosage forms, chemical delivery systems such as prodrugs, the use of cyclodextrins to increase solubility of various drugs, the concept of penetration enhancers and other ocular drug delivery systems such as polymeric gels, bioadhesive hydrogels, in-situ forming gels with temperature-, pH-, or osmotically induced gelation, combination of polymers and colloidal systems such as liposomes, niosomes, cubosomes, microemulsions, nanoemulsions and nanoparticles are discussed. Novel ophthalmic delivery systems propose the use of many excipients to increase the viscosity or the bioadhesion of the product. New formulations like gels or colloidal systems have been tested with numerous active substances by in vitro and in vivo studies. Sustained drug release and increase in drug bioavailability have been obtained, offering the promise of innovation in drug delivery systems for ocular administration. Combining different properties of pharmaceutical formulations appears to offer a genuine synergy in bioavailability and sustained release. Promising results are obtained with colloidal systems which present very comfortable

  11. 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. PMID:27496742

  12. 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

  13. 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. PMID:27279067

  14. 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. PMID:26247118

  15. Nanoscale drug delivery for targeted chemotherapy.

    PubMed

    Xin, Yong; Huang, Qian; Tang, Jian-Qin; Hou, Xiao-Yang; Zhang, Pei; Zhang, Long Zhen; Jiang, Guan

    2016-08-28

    Despite significant improvements in diagnostic methods and innovations in therapies for specific cancers, effective treatments for neoplastic diseases still represent major challenges. Nanotechnology as an emerging technology has been widely used in many fields and also provides a new opportunity for the targeted delivery of cancer drugs. Nanoscale delivery of chemotherapy drugs to the tumor site is highly desirable. Recent studies have shown that nanoscale drug delivery systems not only have the ability to destroy cancer cells but may also be carriers for chemotherapy drugs. Some studies have demonstrated that delivery of chemotherapy via nanoscale carriers has greater therapeutic benefit than either treatment modality alone. In this review, novel approaches to nanoscale delivery of chemotherapy are described and recent progress in this field is discussed. PMID:27235607

  16. Mucoadhesive microspheres containing anti-hypertensive agent: formulation and characterization.

    PubMed

    Patel, Ankita Sunilbhai; Saikat, Pande; Pravinbhai, Patel Ronakkumar

    2014-01-01

    The spherical microspheres consisting of Furosemide loaded sodium alginate and along with HPMC E50 or sodium CMC as mucoadhesive polymers in different ratios were prepared using ionic gelation technique. Calcium chloride was used as crosslinking, to retard the drug release from the mucoadhesive microspheres. The prepared mucoadhesive microspheres were subjected for evaluation of various parameters like production yield, particle size, encapsulation efficiency, mucoadhesion test and in vitro dissolution profile studies. Formulations were subjected to DSC study and SEM analysis. The in vitro release data were well fit into Higuchi and Korsmeyer-Peppas model and followed non-Fickian diffusion mechanism. PMID:24410197

  17. 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. PMID:27301169

  18. 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

  19. Modeling of diffusion controlled drug delivery.

    PubMed

    Siepmann, Juergen; Siepmann, Florence

    2012-07-20

    Mathematical modeling of drug release can be very helpful to speed up product development and to better understand the mechanisms controlling drug release from advanced delivery systems. Ideally, in silico simulations can quantitatively predict the impact of formulation and processing parameters on the resulting drug release kinetics. The aim of this article is to give an overview on the current state of the art of modeling drug release from delivery systems, which are predominantly controlled by diffusional mass transport. The inner structure of the device, the ratio "initial drug concentration:drug solubility" as well as the device geometry determine which type of mathematical equation must be applied. A straightforward "road map" is given, explaining how to identify the appropriate equation for a particular type of drug delivery system. The respective equations for a broad range of devices are indicated, including reservoir and matrix systems, exhibiting or not an initial excess of drug and the geometry of slabs, spheres and cylinders. The assumptions the models are based on as well as their limitations are pointed out. Practical examples illustrate the usefulness of mathematical modeling of diffusion controlled drug delivery. Due to the advances in information technology the importance of in silico optimization of advanced drug delivery systems can be expected to significantly increase in the future. PMID:22019555

  20. Composite bi-layered erodible films for potential ocular drug delivery.

    PubMed

    Boateng, J S; Popescu, A M

    2016-09-01

    Bi-layered hydroxypropylmethylcellulose and Eudragit based films were formulated as potential ocular drug delivery systems using chloramphenicol as a model antibiotic. Films were plasticized with polyethylene glycol 400 present in the Eudragit layer or both Eudragit and hydroxypropylmethylcellulose layers, and loaded with chloramphenicol (0.5% w/v in solution) in the hydroxypropylmethylcellulose layer. The weight, thickness and folding endurance of the optimized formulations were measured and further characterised for transparency, tensile, mucoadhesive, swelling and in vitro drug dissolution properties. The physical form of chloramphenicol within the films was evaluated using differential scanning calorimetry (DSC), and X-ray diffraction (XRD), complimented with scanning electron microscopy and energy dispersive X-ray spectroscopy. Fourier transform infrared spectroscopy was used to assess the interactions between the drug and the film components and confirm chloramphenicol's presence within the sample. Optimum films showed high transparency (≥80% transmittance), ease of peeling from Petri dish and folding endurance above 250. Average thickness was lower than contact lenses (0.4-1mm), confirming them as thin ocular films. The tensile properties showed a good balance between toughness and flexibility, and mucoadhesivity showed that they could potentially adhere to the ocular surface for prolonged periods. The drug loaded films showed swelling capacity that was greater than 300% of their original weight. The physical form of chloramphenicol within the films was amorphous (DSC and XRD) whilst in vitro drug dissolution showed sustained drug release from the films for four hours, before complete erosion. The chloramphenicol loaded films represent a potential means of treating common eye infections. PMID:27214785

  1. 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

  2. Fabrication and in vitro evaluation of mucoadhesive ondansetron hydrochloride beads for the management of emesis in chemotherapy

    PubMed Central

    Malik, Raj Kaur; Malik, Prashant; Gulati, Neha; Nagaich, Upendra

    2013-01-01

    Background Mucoadhesive beads were fabricated and evaluated for controlled release of an antiemetic drug ‘Ondansetron Hydrochloride’. Ondansetron hydrochloride is a serotonin 5-HT3 receptor antagonist mainly used for the treatment of emesis, which occurs as a side effect of chemotherapy. Materials and Methods: The present work was to fabricate and evaluate ondansetron-loaded microbeads by using chitosan as mucoadhesive and sustained release polymer. Sodium tripolyphosphate (Na-TPP) was used as a cross-linking agent. The microbeads were successfully prepared by ionotropic gelation technique. The particle size, entrapment efficiency, and mucoadhesive strength of drug-loaded formulations was measured by an optical microscope, direct crushing method, and in vitro wash-off method, respectively. Results: Particle size, entrapment efficiency, mucoadhesive strength, and in vitro drug release of optimized formulation was found to be 760.11 ± 1.02 μm, 75.09 ± 2.40%, 95.14 ± 0.27% and 87.45 ± 1.21%, respectively. The data was fitted to different kinetic models to illustrate its anomalous (non-Fickian) diffusion. Conclusions: The results revealed that ondansetron HCl loaded microbeads are most suitable mode of drug delivery for promising therapeutic action. Ondansetron HCl-loaded microbeads can prove to be potential pharmaceutical dosage forms for sustaining the drug release and reducing the dose frequency. PMID:23799204

  3. Development and evaluation of tamarind seed xyloglucan-based mucoadhesive buccal films of rizatriptan benzoate.

    PubMed

    Avachat, Amelia M; Gujar, Kishore N; Wagh, Kishor V

    2013-01-16

    Mucoadhesive buccal films were developed using tamarind seed xyloglucan (TSX) as novel mucoadhesive polysaccharide polymer for systemic delivery of rizatriptan benzoate through buccal route. Formulations were prepared based on 3(2) factorial design with concentrations of TSX and carbopol 934P (CP) as independent variables. Three dependent variables considered were tensile strength, bioadhesion force and drug release. DSC analysis revealed no interaction between drug and polymers. Ex vivo diffusion studies were carried out using Franz diffusion cell, while bioadhesive properties were evaluated using texture analyzer with porcine buccal mucosa as model tissue. Results revealed that bilayer film containing 4% (w/v) TSX and 0.5% (w/v) CP in the drug layer and 1% (w/v) ethyl cellulose in backing layer demonstrated diffusion of 93.45% through the porcine buccal mucosa. Thus, this study suggests that tamarind seed polysaccharide can act as a potential mucoadhesive polymer for buccal delivery of a highly soluble drug like rizatriptan benzoate. PMID:23121942

  4. Synthetic micro/nanomotors in drug delivery.

    PubMed

    Gao, Wei; Wang, Joseph

    2014-09-21

    Nanomachines offer considerable promise for the treatment of diseases. The ability of man-made nanomotors to rapidly deliver therapeutic payloads to their target destination represents a novel nanomedicine approach. Synthetic nanomotors, based on a multitude of propulsion mechanisms, have been developed over the past decade toward diverse biomedical applications. In this review article, we journey from the use of chemically powered drug-delivery nanovehicles to externally actuated (fuel-free) drug-delivery nanomachine platforms, and conclude with future prospects and challenges for such practical propelling drug-delivery systems. As future micro/nanomachines become more powerful and functional, these tiny devices are expected to perform more demanding biomedical tasks and benefit different drug delivery applications. PMID:25096021

  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. Drug Delivery Systems: Entering the Mainstream

    NASA Astrophysics Data System (ADS)

    Allen, Theresa M.; Cullis, Pieter R.

    2004-03-01

    Drug delivery systems (DDS) such as lipid- or polymer-based nanoparticles can be designed to improve the pharmacological and therapeutic properties of drugs administered parenterally. Many of the early problems that hindered the clinical applications of particulate DDS have been overcome, with several DDS formulations of anticancer and antifungal drugs now approved for clinical use. Furthermore, there is considerable interest in exploiting the advantages of DDS for in vivo delivery of new drugs derived from proteomics or genomics research and for their use in ligand-targeted therapeutics.

  7. 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. PMID:19569979

  8. Methods of Drug Delivery in Neurotrauma.

    PubMed

    Deng-Bryant, Ying; Readnower, Ryan; Leung, Lai Yee; Tortella, Frank; Shear, Deborah

    2016-01-01

    The central nervous system (CNS) is protected by blood-brain barrier (BBB) and blood-cerebrospinal-fluid (CSF) barrier that limit toxic agents and most molecules from penetrating the brain and spinal cord. However, these barriers also prevent most pharmaceuticals from entering into the CNS. Drug delivery to the CNS following neurotrauma is complicated. Although studies have shown BBB permeability increases in various TBI models, it remains as the key mitigating factor for delivering drugs into the CNS. The commonly used methods for drug delivery in preclinical neurotrauma studies include intraperitoneal, subcutaneous, intravenous, and intracerebroventricular delivery. It should be noted that for a drug to be successfully translated into the clinic, it needs to be administered preclinically as it would be anticipated to be administered to patients. And this likely leads to better dose selection of the drug, as well as recognition of any possible side effects, prior to transition into a clinical trial. Additionally, novel approach that is noninvasive and yet circumvents BBB, such as drug delivery through nerve pathways innervating the nasal passages, needs to be investigated in animal models, as it may provide a viable drug delivery method for patients who sustain mild CNS injury or require chronic treatments. Therefore, the focus of this chapter is to present rationales and methods for delivering drugs by IV infusion via the jugular vein, and intranasally in preclinical studies. PMID:27604714

  9. [Progression of drug delivery system for glaucoma].

    PubMed

    Xu, Yan; Lyu, Liu

    2014-12-01

    Reduction of intraocular pressure (IOP) by drugs is a major treatment for glaucoma. Clinically, diverse antiglaucoma drugs take effect to decrease the IOP through different mechanisms.However, due to limitations of traditional form of eye drops, the bioavailability of the drug and the patient compliance is lowered, the clinical efficacy is not good and also some toxic and side-effects come out.Otherwise, traditional medication is not suitable for neuroprotective drugs to work on both retina and optic nerve. Drug delivery system has the potential to improve the bioavailability of the drug, prolong the time of drug action, decrease the dosage and frequency of drugs, reduce the side-effects, and improve the patient compliance and efficacy.It is one of the most important studies in glaucoma medication development because it is valuable for patients' neuroprotection.Nowadays, several novel delivery systems have been designed. This review will focus on the progressions of some of the sustained-release antiglaucoma eye drops, polymeric gels, colloidal systems, membrane-controlled drug delivery system, ocular implants, and transscleral drug delivery systems. PMID:25619186

  10. Role of microemuslsions in advanced drug delivery.

    PubMed

    Sharma, Aman Kumar; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-06-01

    Microemulsions have gained significant attention from formulation scientists since the time they have been discovered, because of their excellent properties related to their stability, solubility, simplicity, and formulation aspects. The application of microemulsions is not limited to drug delivery via the oral, topical or ocular routes, but may also be seen in cosmetics, immunology, sensor devices, coating, textiles, analytical chemistry, and spermicide. Finally, the objective of this review is to discuss briefly the applications of microemulsions in advanced drug delivery. PMID:25711493

  11. Osmotically controlled drug delivery system with associated drugs.

    PubMed

    Gupta, Brahma Prakash; Thakur, Navneet; Jain, Nishi P; Banweer, Jitendra; Jain, Surendra

    2010-01-01

    Conventional drug delivery systems have slight control over their drug release and almost no control over the effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the controlled or modified release drug delivery systems. They include dosage forms for oral and transdermal administration as well as injectable and implantable systems. For most of drugs, oral route remains as the most acceptable route of administration. Certain molecules may have low oral bioavailability because of solubility or permeability limitations. Development of an extended release dosage form also requires reasonable absorption throughout the gastro-intestinal tract (GIT). Among the available techniques to improve the bioavailability of these drugs fabrication of osmotic drug delivery system is the most appropriate one. Osmotic drug delivery systems release the drug with the zero order kinetics which does not depend on the initial concentration and the physiological factors of GIT. This review brings out new technologies, fabrication and recent clinical research in osmotic drug delivery. PMID:21486532

  12. 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

  13. 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

  14. 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.

  15. 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

  16. Mucoadhesive Gels Designed for the Controlled Release of Chlorhexidine in the Oral Cavity

    PubMed Central

    Fini, Adamo; Bergamante, Valentina; Ceschel, Gian Carlo

    2011-01-01

    This study describes the in vitro/ex vivo buccal release of chlorhexidine (CHX) from nine mucoadhesive aqueous gels, as well as their physicochemical and mucoadhesive properties: CHX was present at a constant 1% w/v concentration in the chemical form of digluconate salt. The mucoadhesive/gel forming materials were carboxymethyl- (CMC), hydroxypropylmethyl- (HPMC) and hydroxypropyl- (HPC) cellulose, alone (3% w/w) or in binary mixtures (5% w/w); gels were tested for their mucoadhesion using the mucin method at 1, 2 and 3% w/w concentrations. CHX release from different formulations was assessed using a USP method and newly developed apparatus, combining release/permeation process in which porcine mucosa was placed in a Franz cell. The combination of HPMC or HPC with CMC showed slower drug release when compared to each of the individual polymers. All the systems proved suitable for CHX buccal delivery, being able to guarantee both prolonged release and reduced transmucosal permeation. Gels were compared for the release of previously studied tablets that contained Carbopol and HPMC, alone or in mixture. An accurate selection and combination of the materials allow the design of different pharmaceutical forms suitable for different purposes, by simply modifying the formulation compositions. PMID:24309302

  17. 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

  18. 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.

  19. 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

  20. Implication of nanofibers in oral drug delivery.

    PubMed

    Kapahi, Himani; Khan, Nikhat Mansoor; Bhardwaj, Ankur; Mishra, Neeraj

    2015-01-01

    Nanofibers has gained significant prominence in recent years due to its wide applications in medicinal pharmacy, textile, tissue engineering and in various drug delivery system. In oral drug delivery system (DDS), nanofibers can be delivered as Nanofiber scaffolds, electrosponge nanofibers as oral fast delivery system, multilayered nanofiber loaded mashes, surface modified cross-linked electrospun nanofibers. Nanofibers are of 50- 1000 nm size fibres having large surface area, high porosity, small pore size, low density. Various approaches for formulation of nanofibers are molecular assembly, thermally induced phase separation, electrospining. Most commonly used by using electrospining polymer nanofibres with different range can be produced collective usage of electro spinning with pharmaceutical polymers offers novel tactics for developing drug delivery system (DDS). Different polymers used in preparation of nanofibers include biodegradable hydrophilic polymers, hydrophobic polymers and amphiphilic polymers. Electrospun nanofibers are often used to load insoluble drugs for enhancing their dissolution properties due to their high surface area per unit mass. Besides the water insoluble drugs freely water soluble sodium can also spun into the fibers. The most commonly polymers used for nanofibers are gelatin, dextran, nylon, polystyrene, polyacrylonitrile, polycarbonate, polyimides, poly vinyl alchol, polybenzimidazole. Delivery systems reviewed rely on temporal control, changes in pH along the GIT, the action of local enzymes to trigger drug release, and changes in intraluminal pressure. Dissolution of enteric polymer coatings due to a change in local pH and reduction of azo-bonds to release an active agent are both used in commercially marketed products. In vitro and in vivo studies have demonstrated that the release rates of drugs from these nanofiber formulations are enhanced compared to those from original drug substance. This review is focused on the different

  1. Electroresponsive nanoparticles for drug delivery on demand.

    PubMed

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

    2016-04-28

    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. PMID:27088543

  2. 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.

  3. 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

  4. Electronics will transform drug delivery devices.

    PubMed

    Mazzoni, Paolo

    2004-03-01

    The drug delivery device sector will be transformed by electronically controlled alternatives that will maximise user safety and medical effectiveness and open the way to the introduction of high-power, next-generation drugs. Current business partnerships will need to change to allow this to happen. PMID:15154333

  5. 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.

  6. 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

  7. Hp-β-CD-voriconazole in situ gelling system for ocular drug delivery: in vitro, stability, and antifungal activities assessment.

    PubMed

    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 (T gel), 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 T gel 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

  8. 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

  9. 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

  10. 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. PMID:23016644

  11. Amorphous powders for inhalation drug delivery.

    PubMed

    Chen, Lan; Okuda, Tomoyuki; Lu, Xiang-Yun; Chan, Hak-Kim

    2016-05-01

    For inhalation drug delivery, amorphous powder formulations offer the benefits of increased bioavailability for poorly soluble drugs, improved biochemical stability for biologics, and expanded options of using various drugs and their combinations. However, amorphous formulations usually have poor physicochemical stability. This review focuses on inhalable amorphous powders, including the production methods, the active pharmaceutical ingredients and the excipients with a highlight on stabilization of the particles. PMID:26780404

  12. Drug Delivery Research: The Invention Cycle.

    PubMed

    Park, Kinam

    2016-07-01

    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. PMID:26962897

  13. 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

  14. Inhaled nano- and microparticles for drug delivery

    PubMed Central

    El-Sherbiny, Ibrahim M.; El-Baz, Nancy M.; Yacoub, Magdi H.

    2015-01-01

    The 21st century has seen a paradigm shift to inhaled therapy, for both systemic and local drug delivery, due to the lung's favourable properties of a large surface area and high permeability. Pulmonary drug delivery possesses many advantages, including non-invasive route of administration, low metabolic activity, control environment for systemic absorption and avoids first bypass metabolism. However, because the lung is one of the major ports of entry, it has multiple clearance mechanisms, which prevent foreign particles from entering the body. Although these clearance mechanisms maintain the sterility of the lung, clearance mechanisms can also act as barriers to the therapeutic effectiveness of inhaled drugs. This effectiveness is also influenced by the deposition site and delivered dose. Particulate-based drug delivery systems have emerged as an innovative and promising alternative to conventional inhaled drugs to circumvent pulmonary clearance mechanisms and provide enhanced therapeutic efficiency and controlled drug release. The principle of multiple pulmonary clearance mechanisms is reviewed, including mucociliary, alveolar macrophages, absorptive, and metabolic degradation. This review also discusses the current approaches and formulations developed to achieve optimal pulmonary drug delivery systems. PMID:26779496

  15. 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. PMID:24567139

  16. Mucoadhesive polyethylenimine-dextran sulfate nanoparticles containing Punica granatum peel extract as a novel sustained-release antimicrobial.

    PubMed

    Tiyaboonchai, Waree; Rodleang, Ingdao; Ounaroon, Anan

    2015-06-01

    Mucoadhesive polyethylenimine-dextran sulfate nanoparticles (PDNPs) were developed for local oral mucosa delivery. Punica granatum peel extract (PGE) was loaded into PDNPs for oral malodor reduction and caries prevention. PDNPs were constructed using the polyelectrolyte complexation technique employing oppositely charged polymers polyethylenimine (PEI) and dextran sulfate (DS), with PEG 400 as a stabilizer. Under optimal conditions, spherical particles of ∼ 500 nm with a zeta potential of ∼+28 mV were produced. Up to 98%, drug entrapment efficiency was observed. The mass ratio of PEI:DS played a significant role in controlling particle size and entrapment efficacy. PDNPs shown to be a good mucoadhesive drug delivery system as confirmed by ex vivo wash off test. In vitro dissolution studies revealed that PGE-loaded PDNPs manifested a prolong release characteristic with a burst release within 5 min. In addition, they remained effectively against oral bacteria. PMID:24438035

  17. Drug Delivery Strategies of Chemical CDK Inhibitors.

    PubMed

    Alvira, Daniel; Mondragón, Laura

    2016-01-01

    The pharmacological use of new therapeutics is often limited by a safe and effective drug-delivery system. In this sense, new chemical CDK inhibitors are not an exception. Nanotechnology may be able to solve some of the main problems limiting cancer treatments such as more specific delivery of therapeutics and reduction of toxic secondary effects. It provides new delivery systems able to specifically target cancer cells and release the active molecules in a controlled fashion. Specifically, silica mesoporous supports (SMPS) have emerged as an alternative for more classical drug delivery systems based on polymers. In this chapter, we describe the synthesis of a SMPS containing the CDK inhibitor roscovitine as cargo molecule and the protocols for confirmation of the proper cargo release of the nanoparticles in cell culture employing cell viability, cellular internalization, and cell death induction studies. PMID:26231714

  18. 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

  19. 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.

  20. Engineered inorganic nanoparticles for drug delivery applications.

    PubMed

    Ojea-Jiménez, Isaac; Comenge, Joan; García-Fernández, Lorena; Megson, Zoë A; Casals, Eudald; Puntes, Victor F

    2013-06-01

    Inorganic nanoparticles (NPs) currently have immense potential as drug delivery vectors due to their unique physicochemical properties such as high surface area per unit volume, their optical and magnetic uniqueness and the ability to be functionalized with a large number of ligands to enhance their affinity towards target molecules. These features, together with the therapeutic activity of some drugs, render the combination of these two entities (NP-drug) as an attractive alternative in the area of drug delivery. One of the major advantages of these conjugates is the possibility to have a local delivery of the drug, thus reducing systemic side effects and enabling a higher efficiency of the therapeutic molecule. This review highlights the direct implications of nanoscale particles in the development of drug delivery systems. In more detail, it is also remarked the extensive use of inorganic NPs for targeted cancer therapies. As the range of nanoparticles and their applications continues to increase, human safety concerns are gaining importance, which makes it necessary to better understand the potential toxicity hazards of these materials. PMID:23116108

  1. 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

  2. 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

  3. 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

  4. 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

  5. Current perspectives on intrathecal drug delivery

    PubMed Central

    Bottros, Michael M; Christo, Paul J

    2014-01-01

    Advances in intrathecal analgesia and intrathecal drug delivery systems have allowed for a range of medications to be used in the control of pain and spasticity. This technique allows for reduced medication doses that can decrease the side effects typically associated with oral or parenteral drug delivery. Recent expert panel consensus guidelines have provided care paths in the treatment of nociceptive, neuropathic, and mixed pain syndromes. While the data for pain relief, adverse effect reduction, and cost-effectiveness with cancer pain control are compelling, the evidence is less clear for noncancer pain, other than spasticity. Physicians should be aware of mechanical, pharmacological, surgical, and patient-specific complications, including possible granuloma formation. Newer intrathecal drug delivery systems may allow for better safety and quality of life outcomes. PMID:25395870

  6. 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

  7. Targeting the brain: advances in drug delivery.

    PubMed

    Blumling Iii, James P; Silva, Gabriel A

    2012-09-01

    The blood-brain barrier (BBB) represents a significant obstacle for drug delivery to the brain. Many therapeutics with potential for treating neurological conditions prove incompatible with intravenous delivery simply because of this barrier. Rather than modifying drugs to penetrate the BBB directly, it has proven more efficacious to either physically bypass the barrier or to use specialized delivery vehicles that circumvent BBB regulatory mechanisms. Controlled-release intracranial polymer implants and particle injections are the clinical state of the art with regard to localized delivery, although these approaches can impose significant surgical risks. Focused ultrasound provides a non-invasive alternative that may prove more desirable for acute treatment of brain tumors and other conditions requiring local tissue necrosis. For targeting the brain as a whole, cell-penetrating peptides (CPPs) and molecular trojan horses (MTHs) have demonstrated particular ability as delivery molecules and will likely see increased application. CPPs are not brain specific but offer the potential for efficient traversal of the BBB, and tandem systems with targeting molecules may produce extremely effective brain drug delivery tools. Molecular trojan horses utilize receptor-mediated transcytosis to transport cargo and are thus limited by the quantity of relevant receptors; however, they can be very selective for the BBB endothelium and have shown promise in gene therapy. PMID:23016646

  8. 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

  9. 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. PMID:26802493

  10. Drug delivery and nanoparticles: Applications and hazards

    PubMed Central

    De Jong, Wim H; Borm, Paul JA

    2008-01-01

    The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells

  11. 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.

  12. 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.

  13. Recent technologies in pulsatile drug delivery systems

    PubMed Central

    Jain, Deepika; Raturi, Richa; Jain, Vikas; Bansal, Praveen; Singh, Ranjit

    2011-01-01

    Pulsatile drug delivery systems (PDDS) have attracted attraction because of their multiple benefits over conventional dosage forms. They deliver the drug at the right time, at the right site of action and in the right amount, which provides more benefit than conventional dosages and increased patient compliance. These systems are designed according to the circadian rhythm of the body, and the drug is released rapidly and completely as a pulse after a lag time. These products follow the sigmoid release profile characterized by a time period. These systems are beneficial for drugs with chronopharmacological behavior, where nocturnal dosing is required, and for drugs that show the first-pass effect. This review covers methods and marketed technologies that have been developed to achieve pulsatile delivery. Marketed technologies, such as PulsincapTM, Diffucaps®, CODAS®, OROS® and PULSYSTM, follow the above mechanism to render a sigmoidal drug release profile. Diseases wherein PDDS are promising include asthma, peptic ulcers, cardiovascular ailments, arthritis and attention deficit syndrome in children and hypercholesterolemia. Pulsatile drug delivery systems have the potential to bring new developments in the therapy of many diseases. PMID:23507727

  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.

  15. 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. PMID:19819318

  16. Aptamers for Targeted Drug Delivery

    PubMed Central

    Ray, Partha; White, Rebekah R.

    2010-01-01

    Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX). SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer-mediated delivery.

  17. 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. PMID:21329048

  18. 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.

  19. Poly(hydroxy acids) in drug delivery.

    PubMed

    Juni, K; Nakano, M

    1987-01-01

    Poly(hydroxy acids) so far have been examined for use in drug delivery in limited number, while the advantageous use of the polymers has been recognized due to their biodegradability and biocompatibility. Homo- and copolymers of lactic acid and glycolic acid have been studied in drug delivery by many workers, while homo- and copolymers of epsilon-caprolactone have been studied by only one group of workers. Although poly-hydroxybutyric acid had been found to be a naturally occurring polymer, examination as to the use of the polymer in drug delivery is rather recent and reports are still limited. In the present article, the use of poly(hydroxy acids) including homo- and copolymers of lactic acid and glycolic acid, polycaprolactone, and poly-beta-hydroxybutyric acid in drug delivery is reviewed. Physicochemical properties, biodegradability, and biocompatibility of the polymers, and evaluations in vitro and in vivo of specific dosage forms using the polymers, are included. The most recent work in our laboratories on the use of polyactic acid and poly-beta-hydroxybutyric acid is also included. PMID:3549007

  20. 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

  1. Strategies for antimicrobial drug delivery to biofilm.

    PubMed

    Martin, Claire; Low, Wan Li; Gupta, Abhishek; Amin, Mohd Cairul Iqbal Mohd; Radecka, Iza; Britland, Stephen T; Raj, Prem; Kenward, Ken M A

    2015-01-01

    Biofilms are formed by the attachment of single or mixed microbial communities to a variety of biological and/or synthetic surfaces. Biofilm micro-organisms benefit from many advantages of the polymicrobial environment including increased resistance against antimicrobials and protection against the host organism's defence mechanisms. These benefits stem from a number of structural and physiological differences between planktonic and biofilm-resident microbes, but two main factors are the presence of extracellular polymeric substances (EPS) and quorum sensing communication. Once formed, biofilms begin to synthesise EPS, a complex viscous matrix composed of a variety of macromolecules including proteins, lipids and polysaccharides. In terms of drug delivery strategies, it is the EPS that presents the greatest barrier to diffusion for drug delivery systems and free antimicrobial agents alike. In addition to EPS synthesis, biofilm-based micro-organisms can also produce small, diffusible signalling molecules involved in cell density-dependent intercellular communication, or quorum sensing. Not only does quorum sensing allow microbes to detect critical cell density numbers, but it also permits co-ordinated behaviour within the biofilm, such as iron chelation and defensive antibiotic activities. Against this backdrop of microbial defence and cell density-specific communication, a variety of drug delivery systems have been developed to deliver antimicrobial agents and antibiotics to extracellular and/or intracellular targets, or more recently, to interfere with the specific mechanisms of quorum sensing. Successful delivery strategies have employed lipidic and polymeric-based formulations such as liposomes and cyclodextrins respectively, in addition to inorganic carriers e.g. metal nanoparticles. This review will examine a range of drug delivery systems and their application to biofilm delivery, as well as pharmaceutical formulations with innate antimicrobial properties

  2. Nasal administration of liquid crystal precursor mucoadhesive vehicle as an alternative antiretroviral therapy.

    PubMed

    Carvalho, Flávia Chiva; Campos, Michel Leandro; Peccinini, Rosângela Gonçalves; Gremião, Maria Palmira Daflon

    2013-05-01

    The purpose of this study was to develop a mucoadhesive stimuli-sensitive drug delivery system for nasal administration of zidovudine (AZT). The system was prepared by formulating a low viscosity precursor of a liquid crystal phase, taking advantage of its lyotropic phase behavior. Flow rheology measurements showed that the formulation composed of PPG-5-CETETH-20, oleic acid and water (55, 30, 15% w/w), denominated P, has Newtonian flow behavior. Polarized light microscopy (PLM) revealed that formulation P is isotropic, whereas its 1:1 (w/w) dilution with artificial nasal mucus (ANM) changed the system to an anisotropic lamellar phase (PD). Oscillatory frequency sweep analysis showed that PD has a high storage modulus (G') at nasal temperatures. Measurement of the mucoadhesive force against excised porcine nasal mucosa or a mucin disk proved that the transition to the lamellar phase tripled the work of mucoadhesion. Ex vivo permeation studies across porcine nasal mucosa exhibited an 18-fold rise in the permeability of AZT from the formulation. The Weibull mathematical model suggested that the AZT is released by Fickian diffusion mechanisms. Hence, the physicochemical characterization, combined with ex vivo studies, revealed that the PPG-5-CETETH-20, oleic acid, and water formulation could form a mucoadhesive matrix in contact with nasal mucus that promoted nasal absorption of the AZT. For an in vivo assessment, the plasma concentrations of AZT in rats were determined by HPLC method following intravenous and intranasal administration of AZT-loaded P formulation (PA) and AZT solution, respectively, at a dose of 8mg/kg. The intranasal administration of PA resulted in a fast absorption process (Tmax=6.7min). Therefore, a liquid crystal precursor formulation administered by the nasal route might represent a promising novel tool for the systemic delivery of AZT and other antiretroviral drugs. In the present study, the uptake of AZT absorption in the nasal mucosa was

  3. Fluorescence optical imaging in anticancer drug delivery.

    PubMed

    Etrych, Tomáš; Lucas, Henrike; Janoušková, Olga; Chytil, Petr; Mueller, Thomas; Mäder, Karsten

    2016-03-28

    In the past several decades, nanosized drug delivery systems with various targeting functions and controlled drug release capabilities inside targeted tissues or cells have been intensively studied. Understanding their pharmacokinetic properties is crucial for the successful transition of this research into clinical practice. Among others, fluorescence imaging has become one of the most commonly used imaging tools in pre-clinical research. The development of increasing numbers of suitable fluorescent dyes excitable in the visible to near-infrared wavelengths of the spectrum has significantly expanded the applicability of fluorescence imaging. This paper focuses on the potential applications and limitations of non-invasive imaging techniques in the field of drug delivery, especially in anticancer therapy. Fluorescent imaging at both the cellular and systemic levels is discussed in detail. Additionally, we explore the possibility for simultaneous treatment and imaging using theranostics and combinations of different imaging techniques, e.g., fluorescence imaging with computed tomography. PMID:26892751

  4. Matrix metalloproteases: Underutilized targets for drug delivery

    PubMed Central

    Vartak, Deepali G.; Gemeinhart, Richard A.

    2013-01-01

    Pathophysiological molecules in the extracellular environment offer excellent targets that can be exploited for designing drug targeting systems. Matrix metalloproteases (MMPs) are a family of extracellular proteolytic enzymes that are characterized by their overexpression or overactivity in several pathologies. Over the last two decades, the MMP literature reveals heightened interest in the research involving MMP biology, pathology, and targeting. This review describes various strategies that have been designed to utilize MMPs for targeting therapeutic entities. Key factors that need to be considered in the successful design of such systems have been identified based on the analyses of these strategies. Development of targeted drug delivery using MMPs has been steadily pursued; however, drug delivery efforts using these targets need to be intensified and focused to realize the clinical application of the fast developing fundamental MMP research. PMID:17365270

  5. 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

  6. A Molecular Communications Model for Drug Delivery.

    PubMed

    Femminella, Mauro; Reali, Gianluca; Vasilakos, Athanasios V

    2015-12-01

    This paper considers the scenario of a targeted drug delivery system, which consists of deploying a number of biological nanomachines close to a biological target (e.g., a tumor), able to deliver drug molecules in the diseased area. Suitably located transmitters are designed to release a continuous flow of drug molecules in the surrounding environment, where they diffuse and reach the target. These molecules are received when they chemically react with compliant receptors deployed on the receiver surface. In these conditions, if the release rate is relatively high and the drug absorption time is significant, congestion may happen, essentially at the receiver site. This phenomenon limits the drug absorption rate and makes the signal transmission ineffective, with an undesired diffusion of drug molecules elsewhere in the body. The original contribution of this paper consists of a theoretical analysis of the causes of congestion in diffusion-based molecular communications. For this purpose, it is proposed a reception model consisting of a set of pure loss queuing systems. The proposed model exhibits an excellent agreement with the results of a simulation campaign made by using the Biological and Nano-Scale communication simulator version 2 (BiNS2), a well-known simulator for molecular communications, whose reliability has been assessed through in vitro experiments. The obtained results can be used in rate control algorithms to optimally determine the optimal release rate of molecules in drug delivery applications. PMID:26529770

  7. 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. PMID:26486348

  8. 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.

  9. 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

  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