Novel diethanolamine-grafted high-methoxyl pectin (DGP)-arabic gum (AG) modified montmorillonite (MMT) composites were developed for intragastric ziprasidone HCl (ZIP) delivery by combining floating and mucoadhesion mechanisms. The ZIP-loaded clay-biopolymer matrices were accomplished by ionotropic gelation protocol utilizing zinc acetate in the presence or absence of covalent crosslinker, glutaraldehyde (GA). Various formulations exhibited excellent drug entrapment efficiency (DEE, %) and sustained drug release profiles, which were influenced by the polymer-blend (DGP:AG) ratios, reinforcing filler (MMT) existence and crosslinking procedure. The optimal composites (F-3) demonstrated DEE of 61% and Q8h of 52% with outstanding buoyancy, mucin adsorption ability and biodegradability. The release profile of F-3 was best fitted in the Korsmeyer-Peppas model with Fickian diffusion driven mechanism. The mucin adsorption to composites F-3 followed Freundlich isotherms. The molar mass between crosslinks of composites (F-3) calculated employing Flory-Rehner equation was increased with temperature. Moreover, the thermal, X-ray and infrared analyses confirmed a compatible environment of drug in the composites, except certain extent of transformation of the crystalline drug to its amorphous form. The SEM studies revealed the spherical morphology of the composites. Thus, the newly developed DGP-AG-MMT composites are appropriate for gastroretentive ZIP delivery over an extended period of time.
Curcumin, which is derived from turmeric has gained much attention in recent years for its anticancer activities against various cancers. However, due to its poor absorption, rapid metabolism and elimination, curcumin has a very low oral bioavailability. Therefore, we have formulated mucoadhesive nanoparticles to deliver curcumin to the colon, such that prolonged contact between the nanoparticles and the colon leads to a sustained level of curcumin in the colon, improving the anticancer effect of curcumin on colorectal cancer. The current work entails the ex vivo mucoadhesion study of the formulated nanoparticles and the in vitro effect of mucoadhesive interaction between the nanoparticles and colorectal cancer cells. The ex vivo study showed that curcumin-containing chitosan nanoparticles (CUR-CS-NP) have improved mucoadhesion compared to unloaded chitosan nanoparticles (CS-NP), suggesting that curcumin partly contributes to the mucoadhesion process. This may lead to an enhanced anticancer effect of curcumin when formulated in CUR-CS-NP. Our results show that CUR-CS-NP are taken up to a greater extent by colorectal cancer cells, compared to free curcumin. The prolonged contact offered by the mucoadhesion of CUR-CS-NP onto the cells resulted in a greater reduction in percentage cell viability as well as a lower IC50, indicating a potential improved treatment outcome. The formulation and free curcumin appeared to induce cell apoptosis in colorectal cancer cells, by arresting the cell cycle at G2/M phase. The superior anticancer effects exerted by CUR-CS-NP indicated that this could be a potential treatment for colorectal cancer.
To investigate the suitability of an SCMC (sodium carboxymethyl cellulose/polyethylene glycol 400/carbopol 934P) and an HPMC (hydroxypropylmethyl cellulose/polyethylene glycol 400/carbopol 934P) films as drug vehicle for buccal delivery.
Oral delivery of amphotericin B (AmpB) is desirable because it provides a more patient-friendly mode of administration compared to the current delivery approach akin with the marketed AmpB formulations. The goal of the study was to investigate the pharmacokinetics and tissue distribution of orally administered chitosan-coated AmpB-loaded nanostructured lipid carriers (ChiAmpB NLC) administered to Sprague Dawley rats at a dose of 15 mg/kg. Orally administered ChiAmpB NLC resulted in a two-fold increase in the area under the curve (AUC0-∞) compared to the uncoated AmpB NLC and marketed Amphotret®. This enhanced bioavailability of AmpB suggests prolonged transit and retention of ChiAmpB NLC within the small intestine through mucoadhesion and subsequent absorption by the lymphatic pathway. The results show that mean absorption and residence times (MAT & MRT) were significantly higher from ChiAmpB NLC compared to the other two formulations, attesting to the mucoadhesive effect. The ChiAmpB NLC presented a lower nephrotic accumulation with preferential deposition in liver and spleen. Thus, the limitations of current marketed IV formulations of AmpB are potentially addressed with the ChiAmpB NLC in addition to utilizing this approach for targeting internal organs in visceral leishmaniasis.
Adhesion of the barley husk to the underlying caryopsis requires the development of a cuticular cementing layer on the caryopsis surface. Differences in adhesion quality among genotypes have previously been correlated with cementing layer composition, which is thought to influence caryopsis cuticle permeability, the hypothesised mechanism of adhesion mediation. It is not yet known whether differences in adhesion quality among genotypes are determined by changes in caryopsis cuticle permeability. We examined changes in candidate cementing layer biosynthetic and regulatory genes to investigate the genetic mechanisms behind husk adhesion quality. We used both commercially relevant UK malting cultivars and older European lines to ensure phenotypic diversity in adhesion quality. An ethylene responsive transcription factor (NUD) is required for the development of the cementing layer. To examine correlations between gene expression, cementing layer permeability and husk adhesion quality we also treated cultivars with ethephon (2-chloroethylphosphonic acid) which breaks down to ethylene, and silver thiosulphate which inhibits ethylene reception, and measured caryopsis cuticle permeability. Differential adhesion qualities among genotypes are not determined by NUD expression during development of the cementing material alone, but could result from differences in biosynthetic gene expression during cementing layer development in response to longer-term NUD expression patterns. Altered caryopsis cuticle permeability does result in altered adhesion quality, but the correlation is not consistently positive or negative. Cuticle permeability is therefore not the mechanism that determines husk adhesion quality, but is likely a consequence of the required cuticular compositional changes that determine adhesion.
Blood compatibility of metallocene polyethylene (mPE) was investigated after modifying the surface using hydrochloric acid. Contact angle of the mPE exposed to HCl poses a decrease in its value which indicates increasing wettability and better blood compatibility. Surface of mPE analyzed by using FTIR revealed no significant changes in its functional groups after treatment. Furthermore, scanning electron microscope images supported the increasing wettability through the modifications like pit formations and etching on the acid rendered surface. To evaluate the effect of acid treatment on the coagulation cascade, prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. Both PT and APTT were delayed significantly (P < 0.05) after 60 min exposure implying improved blood compatibility of the surfaces. Hemolysis assay of the treated surface showed a remarkable decrease in the percentage of lysis of red blood cells when compared with untreated surface. Moreover, platelet adhesion assay demonstrated that HCl exposed surfaces deter the attachment of platelets and thereby reduce the chances of activation of blood coagulation cascade. These results confirmed the enhanced blood compatibility of mPE after HCl exposure which can be utilized for cardiovascular implants like artificial vascular prostheses, implants, and various blood contacting devices.
Controlled release buccal patches were fabricated using Eudragit NE40D and studied. Various bioadhesive polymers, namely hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose and Carbopol of different grades, were incorporated into the patches, to modify their bioadhesive properties as well as the rate of drug release, using metoprolol tartrate as the model drug. The in-vitro drug release was determined using the USP 23 dissolution test apparatus 5 with slight modification, while the bioadhesive properties were evaluated using texture analyzer equipment with chicken pouch as the model tissue. The incorporation of hydrophilic polymers was found to affect the drug release as well as enhance the bioadhesiveness. Although high viscosity polymers can enhance the bioadhesiveness of the patches, they also tend to cause non-homogeneous distribution of the polymers and drug, resulting in non-predictable drug-release rates. Of the various bioadhesive polymers studied, Cekol 700 appeared to be most satisfactory in terms of modifying the drug release and enhancement of the bioadhesive properties.
Parkinson disease (PD) is a common, progressive neurodegenerative disorder, characterized by marked depletion of striatal dopamine and degeneration of dopaminergic neurons in the substantia nigra.
The objectives of present research were to develop and characterize thermosensitive and mucoadhesive polymer-based sustained release moxifloxacin in situ gels for the treatment of periodontal diseases. Poloxamer- and chitosan-based in situ gels are in liquid form at room temperature and transform into gel once administered into periodontal pocket due to raise in temperature to 37 °C. Besides solution-to-gel characteristic of polymers, their mucoadhesive nature aids the gel to adhere to mucosa in periodontal pocket for prolonged time and releases the drug in sustained manner. These formulations were prepared using cold method and evaluated for pH, solution-gel temperature, syringeability and viscosity. In vitro drug release studies were conducted using dialysis membrane at 37 °C and 50 rpm. Antimicrobial studies carried out against Aggregatibacter actinomycetemcomitans (A.A.) and Streptococcus mutans (S. Mutans) using agar cup-plate method. The prepared formulations were clear and pH was at 7.01-7.40. The viscosity of formulations was found to be satisfactory. Among the all, formulations comprising of 21% poloxamer 407 and 2% poloxamer 188 (P5) and in combination with 0.5% HPMC (P6) as well as 2% chitosan and 70% β-glycerophosphate (C6) demonstrated an ideal gelation temperature (33-37 °C) and sustained the drug release for 8 h. Formulations P6 and C6 showed promising antimicrobial efficacy with zone of inhibition of 27 mm for A.A. and 55 mm for S. Mutans. The developed sustained release in situ gel formulations could enhance patient's compliance by reducing the dosing frequency and also act as an alternative treatment to curb periodontitis.
The aim of this study was to assess the effects of four enamel preparation techniques on shear bond strength (SBS) of brackets bonded with a resin-modified glass ionomer cement (RMGIC). Adhesive Remnant Index (ARI) and enamel surface roughness (Ra) were also investigated after cement removal.
The tight junctions between capillary endothelial cells of the blood-brain barrier (BBB) restricts the entry of therapeutics into the brain. Potential of the intranasal delivery tool has been explored in administering the therapeutics directly to the brain, thus bypassing BBB. The objective of this study was to develop and optimize an intranasal mucoadhesive nanoemulsion (MNE) of asenapine maleate (ASP) in order to enhance the nasomucosal adhesion and direct brain targetability for improved efficacy and safety. Box-Behnken statistical design was used to recognize the crucial formulation variables influencing droplet size, size distribution and surface charge of ASP-NE. ASP-MNE was obtained by incorporating GRAS mucoadhesive polymer, Carbopol 971 in the optimized NE. Optimized ASP-MNE displayed spherical morphology with a droplet size of 21.2 ± 0.15 nm and 0.355 polydispersity index. Improved ex-vivo permeation was observed in ASP-NE and ASP-MNE, compared to the ASP-solution. Finally, the optimized formulation was found to be safe in ex-vivo ciliotoxicity study on sheep nasal mucosa. The single-dose pharmacokinetic study in male Wistar rats revealed a significant increase in concentration of ASP in the brain upon intranasal administration of ASP-MNE, with a maximum of 284.33 ± 5.5 ng/mL. The time required to reach maximum brain concentration (1 h) was reduced compared to intravenous administration of ASP-NE (3 h). Furthermore, it has been established during the course of present study, that the brain targeting capability of ASP via intranasal administration had enhanced drug-targeting efficiency and drug-targeting potential. In the animal behavioral studies, no extrapyramidal symptoms were observed after intranasal administration of ASP-MNE, while good locomotor activity and hind-limb retraction test established its antipsychotic activity in treated animals. Thus, it can be concluded that the developed intranasal ASP-MNE could be used as an effective and safe tool for brain targeting of ASP in the treatment of psychotic disorders.