Drug Delivery Letters - Volume 9, Issue 1, 2019

Background: Many efforts have been explored in the last decade to treat colon cancer but nanoparticulate drug delivery systems are making a vital contribution in the improvement of drug delivery to colon cancer cells. Objective: In this review, we attempt to highlight recent advancements in the development of novel drug delivery systems of nanoparticles for the targeted drug delivery to colon. Polymers like Epithelial Cell Adhesion Molecule (EpCAM) aptamer chitosan, Hyaluronic Acid (HA), Chitosan (CS)– Carboxymethyl Starch (CMS), silsesquioxane capped mesoporous silica, Near IR (NIR) fluorescent Human Serum Albumin (HAS), poly(ethylene glycol)-conjugated hyaluronic acid etc. have been discussed by employing various anticancer drugs like doxorubicin, oxaliplatin, paclitaxel, 5-fluorouracil etc. Conclusion: These novel drug delivery systems have been determined to be more efficacious in terms of stability, sustained and targeted drug delivery, therapeutic efficacy, improved bioavailability and enhanced anticancer activity.

Introduction: Degree of skin penetration of topical drugs and cosmetics is a crucial point concerning their effects and tolerability. For testing drug delivery across the dermal barrier different in vitro and in vivo assays have been developed. Caffeine has been shown to have beneficial effects against skin aging, sunburn and hair-loss, and it is protective against melanoma and non-melanoma type skin cancers. Aim of our study was to set up an assay system to evaluate caffeine penetration from topical formulation into the skin. Methods: Franz diffusion cells consisting of either a filter paper or an artificial membrane or rat skin were used as in vitro/ex vivo test systems and transdermal microdialysis in anaesthetized rats was performed as an in vivo assay. Results: Results indicate that Franz diffusion cell studies provide a good approximation of the release of caffeine from the formulation but are not able to differentiate between 2% and 4% cream concentrations. The maximum concentrations (Cmax) in case of the 2% cream formulation were 708.3 (2.7 μm pore), 78.7 (0.8 μm pore), 45.3 (0.45 μm pore) and 44.9 (rat skin) μg/7.5 mL, respectively. The in vivo microdialysis experiments were in accordance with the in vitro and ex vivo results and gave more information on the dynamics and follicular and transcellular phases of drug penetration through the layers of the skin. Discussion and Conclusion: Taken together, Franz diffusion cell and transdermal microdialysis are a good combination to evaluate caffeine release and penetration into the skin from the formulations tested. This system might also be used for rapid testing of other hydrophilic topical drugs and has a benefit in the prediction for human skin absorption and tolerability studies, in an early phase of drug development.

Background and Objectives: Dermatophytosis (topical fungal infection) is the 4th common disease in the last decade, affecting 20-25% world’s population. Patients of AIDS, cancer, old age senescence, diabetes, cystic fibrosis become more vulnerable to dermatophytosis. The conventional topical dosage proves effective as prophylactic in preliminary stage. In the advanced stage, the therapeutics interacts with healthy tissues before reaching the pathogen site, showing undesirable effects, thus resulting in pitiable patient compliance. The youngest carbon nano-trope “Graphene” is recently used to manipulate bioactive agents for therapeutic purposes. Here, we explore graphene via smart engineering by virtue of high surface area and high payload for therapeutics and developed graphene–ketoconazole nanohybrid (Gn-keto) for potent efficacy towards dermatophytes in a controlled manner. Methods: Polymethacrylate derivative Eudragit (ERL100 and ERS 100) microspheres embedded with keto and Gn-keto nanohybrid were formulated and characterized through FTIR, TGA, and SEM. In vitro drug release and antifungal activity of formulated Gn-keto microspheres were assessed for controlled release and better efficacy against selected dermatophytes. Results: Presence of numerous pores within the surface of ERL100 microspheres advocated enhanced solubility and diffusion at the site of action. Controlled diffusion across the dialysis membrane was observed with ERS100 microspheres owing to the nonporous surface and poor permeability. Antifungal activity against T. rubrum and M. canis using microdilution method focused on a preeminent activity (99.785 % growth inhibition) of developed nanohybrid loaded microspheres as compared to 80.876% of keto loaded microspheres for T. rubrum. The culture of M. canis was found to be less susceptible to formulated microspheres. Conclusion: Synergistic antifungal activity was achieved by nanohybrid Gn-Keto loaded microspheres against selected topical fungal infections suggesting a vital role of graphene towards fungi.

Objective: Rheumatoid arthritis is a dreaded disease, characterized by pain, inflammation and stiffness of joints, leading to severe immobility problems. The disease shows circadian variation and usually gets aggravated in early morning hours. Aceclofenac, a BCS Class II compound is routinely used in the treatment of pain and inflammation associated with rheumatoid arthritis. The objective of this study was to develop an osmotic delivery system of Aceclofenac that after administration at bedtime would deliver the drug in the morning hours. Methods: A series of osmotically controlled systems of aceclofenac was developed by using lactose, sodium chloride and hydroxypropyl methylcellulose K100M as osmogens. Cellulose acetate (2% w/v in acetone) with varying concentrations of polyethylene glycol-400 was used as the coating polymer to create semi permeable membrane and dissolution was carried out in 290 mOsm phosphate buffer. Formulation optimization was done from four considerations: cumulative release at the end of 6 hours (lag time), cumulative release at the end of 7 hours (burst time), steady state release rate and completeness of drug release. Results: A formulation having swelling polymer hydroxypropyl methylcellulose in the core and lactose and sodium chloride as osmogens, polyethylene glycol-400 (16.39 %) as pore former, with a coating weight of 5% was a close fit to the target release profile and was chosen as the optimum formulation. Conclusion: Aceclofenac tablets containing lactose, HPMC and sodium chloride in the core, given a coating of cellulose acetate and PEG-400 (5% wt gain), generated a release profile for optimum management of rheumatoid arthritic pain.

Background and Objective: Upon oral administration domeperidone is rapidly absorbed, but subjected to the first pass effect which lowers systemic bioavailability to 15%. Mucoadhesive tablet can remain attached to buccal mucosa and becomes capable of bypassing hepatic first-pass metabolism to improve absorption directly into systemic circulation. The present research work was carried with an aim to develop, evaluate and optimize mucoadhesive tablet containing domperidone (DOME) for buccal delivery using different bio-adhesive polymeric combinations. Methods: The buccal tablets were formulated by wet granulation method using isopropyl alcohol. The preliminary formulations were prepared using combinations of HPMC K4, HPMC K15, HPMC K100, HPMC E5 as mucoadhesive polymers. 32 full factorial design was applied to determine the effect of independent variables like concentration of mucoadhesive polymers (HPMC K15 and HPMC K100) over dependent variables like mucoadhesive properties (swelling index, bioadhesive strength and in vitro drug release). The prepared mucoadhesive tablets were evaluated for their tablet properties and mucoadhesive properties. The interactions between drug and polymers were studied by Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). Results: All formulations of factorial design showed satisfactory physicochemical, mechanical and bioadhesive characteristics. The formulation F9 exhibited maximum cumulative drug release, mucoadhesive strength and swelling index. Conclusion: The developed buccal tablet of domperidone might prove alternative to bypass the hepatic first pass metabolism and to avoid degradation which in turn may result in reducing the frequency of administration. Thus, mucoadhesive tablet of domeperidone may become viable alternative overcoming the side effects; achieving greater therapeutic effectiveness and improving the patient compliance.

Background and Objective: The H. pylori infection causes chronic inflammation and significantly increases the risk of developing duodenal and gastric ulcer disease and gastric cancer. Infection with H. pylori is the well-known risk factor for gastric cancer. It is highly desirable to develop a delivery system that localizes the antibiotic at the site of infection to achieve bactericidal concentration for a longer period of time. Thus, present work aimed to develop Concanavalin-A (Con-A) conjugated gastro-retentive microspheres of polymethylmethacrylate (PMMA) and polyethylene oxide (PEO) containing berberine hydrochloride (BBR) for the treatment of H. pylori infection. Methods: Microspheres were prepared by solvent evaporation method and characterized by particles size distribution, surface morphology, % drug entrapment and in vitro drug release in the simulated gastric fluid. Optimized microspheres were conjugated with Con-A and further characterized for Con-A conjugation efficiency, in vitro drug release and ex vivo mucoadhesive properties. Results and Conclusion: Enhanced mucoadhesion (88±1.9%) was shown by Con-A conjugated microspheres as compared with non-conjugated microspheres (14.5±3.6%). This significant difference (p<0.05) in the mucoadhesion may be due to affinity of the Con-A towards glycoproteins of mucus membrane of stomach. Attachment of lectin (Con-A) to the microspheres significantly enhanced the mucoadhesiveness as well as also controlled the berberine release for 10 h study period. The preliminary results from this study advised that Con-A conjugated PMMA and PEO microspheres could be used to incorporate some more herbal drugs and may be used for oral administration against H. pylori in the stomach.

Background: Destroying hydrophobicity and increasing bioavailability of anticancer drugs is emerging field in biomedical nanotherapy. Methods: The porous and oval shaped Gd2O3 gadolinite nanoparticles were synthesized and surface functionalized with folate groups using wet coprecipitation method. The presence of spinal nanophase with Gd2O3 lattice inside nanoparticles was confirmed by the use of XRD pattern and supportive FTIR spectrum. XRD data of nanocomposites proved the spinal core of gadolinite phase even after surface tailoring. These porous nanoparticles were loaded with anticancer drug 5-flurouracil for enhancement of anticancer activity on breast cancer MCF-7 cells. The elemental, optical, morphological and phase physicochemical characterization of the nanomaterials were performed using techniques such as PL, FTIR, XRD spectrometry, TGA thermal analysis, SEM and TEM microscopic analysis. The photoactive biocompatibility of nanohybrids was elaborated on gram positive S. aureus bacteria by agar well antibacterial screening in dark and light. Results: The nanocomposites not only exhibited photoactive biocompatibility but also pH responsive in vitro delivery applied for anticancer therapy on the basis of spectrometric assay following sustained release with zero order Peppas release kinetics. Conclusion: The nanocomposites exhibited higher anticancer activity on MCF-7 cells than free drug and nanohybrids after in vitro MTT assay. These 5-FU loaded folate targeted luminescent and photoactive nanocomposites with gadolinite core find applications in the future biomedical cell-particle interface.

Background and Objective: Gastroesophageal reflux disease (GERD) is one of the most common GIT disorders in which reflux of the GIT contents occurs into the esophagus. The present study is focused on developing a dual component tablet containing a sustained release floating layer of Baclofen and delayed release microspheres of Rabeprazole sodium for the effective treatment of Gastroesophageal Reflux Disease (GERD). Methods:Dual component tablets have been developed to achieve a controlled delivery of two different drugs. Microspheres were prepared by the emulsion solvent evaporation method using different ratios of Eudragit S100 and Rabeprazole sodium (3:1, 6:1, 9:1 and 12:1) and optimized using various parameters. Baclofen floating tablets were prepared by the wet granulation method by using different polymers like sodium alginate (S1), pectin (S2) and guar gum (S3) and characterized for their floating properties and in-vitro drug release study. Results: The cumulative percentage drug release after 9 hrs was found to be in the range of 46.18 to 65.78% for different microsphere formulations. The result showed that, as the amount of polymer increased, the particle size and % yield were also increased, and drug release and entrapment efficiency were decreased. Among all the formulations, M2 was considered as the best because it showed highest entrapment efficiency. Among baclofen floating tablet formulations, S1 was resulted as optimized formulation because it sustained the drug release up to 8 hrs and showed 64.82±0.82% drug release. Conclusion: From the above optimized formulations bilayer tablets containing floating layer of Baclofen and Rabeprazole sodium loaded microspheres layer were prepared by single-punch tablet machine and evaluated for the weight variation, hardness, thickness, diameter, friability, floating time etc. The results of the study showed that all parameters were within pharmacopoeial limits.