Current Drug Therapy (v.6, #2)

Gels and Jellies as a Dosage Form for Dysphagia Patients: A Review by Dixit A. Satyanarayana, Parthasarathi K. Kulkarni, Hosakote G. Shivakumar (79-86).
Patient compliance and safety is now prominent on the agenda of healthcare companies. Dysphagia (swallowingdysfunction) is common in general populations and more common in elderly institutionalized patients and personsin long-term care facilities due to significant primary illnesses, including cerebrovascular accidents, neurodegenerativedisorders, head and neck cancer, or head injury. To ensure safety during oral medication administration, patientswith dysphagia require an appropriate oral dosage form or modification of the dosage form. However inappropriatedrug administration in patients with dysphagia (i.e., the crushing of sustained-release or enteric-coated tablets orthe administration of oral medications with water) is undesirable and may be associated with adverse events (e.g. chokingepisodes, adverse drug reactions resulting from the immediate release of drug from a sustained-release product, refusalto take medications). Hence, there is a need of alternative novel oral dosage form like gels and jellies to deliver drugshaving a viscosity that can be easily swallowed without any discomfort to the patient preventing choking and suffocation.Hence, today the potential for such dosage form is promising because of patient compliance and improved quality oflife. This review briefly describes the role of gels and jellies in dysphagia patients, its advantages and disadvantages,formulation considerations, evaluation parameters and reviews of gels and jellies for dysphagia patients which have beencarried out.

Nanoparticles, Promising Carriers in Drug Targeting: A Review by Yaduvanshi M. Ram, Hemant K.S. Yadav, Mangla N. Singh, Hosakote G. Shivakumar (87-96).
Nanotechnology (derived from the Greek word nano meaning dwarf) is generally defined as the science andengineering of constructing and assembling objects on a scale smaller than one hundred nanometers. Nanotechnology isa multidisciplinary scientific field undergoing explosive development. Nanoparticles are colloidal systems of submicron(< 1 iM) size that can be constructed from a large variety of materials in a large variety of compositions. Commonlydefined nanoparticle vectors include: liposomes, micelles, dendrimers, solid lipid nanoparticles, metallic nanoparticles,semiconductor nanoparticles and polymeric nanoparticles. Nanoparticles have been considered as effective deliverysystems for many reasons including: (i) sufficient physical and biological stability that may facilitate drug entrapment andcontrolled release; (ii) good tolerability of the components; (iii) simplicity of the formulation processing; and (iv) possibilityof scaling up the formulation process. Therefore, nanoparticles have been extensively employed to deliver drugs,genes, vaccines and diagnostics into specific cells/tissues.Site-specific delivery of drug receives a lot of attention because it can reduce drug toxicity and increase therapeuticeffects. To solve the problem of site-specific targeting for the colloidal systems, some authors have attempted to increasethe tissue specificity of colloidal drug carriers by coupling targeting agents. In recent years the improvement of drugtherapy in terms of a more controlled body distribution to reduce side effects was focused. Different new drug carriersystems in the micro- and nanometer size range were generated to overcome these problems. In principle, four differentschemes of drug targeting are conceivable: firstly, a direct application of the drug to the pathological site which inmost cases is not possible; secondly, passive targeting depending on carrier system accumulation in areas with leakyvasculature showing an enhanced permeability and retention effect (EPR-effect); thirdly, employment of physical effectslike varying pH values, differences in temperature or magnetic systems, and finally as the most promising strategy the useof specific vector molecules such as antibodies representing the most universal approach .The objective of this review was to emphasize on drug targeting and various approaches of drug targeting throughnanoparticles.

Palliative Tumor Control by Trabectedin in Pediatric Advanced Sarcoma by Roula A. Farah, Soumana C. Nasser, Racha A. Sabbagh, Pele B. Dina, Toufic A. Eid (97-99).
Refractory soft tissue sarcomas carry a poor prognosis and limited treatment options require the use of newchemotherapeutic agents. We report the case of an eight year old boy with non metastatic alveolar rhabdomyosarcoma ofthe right forearm (Group 3, Stage III). After treatment failure of several chemotherapeutic regimens and progression of hisdisease, Trabectedin was administered at 1.3 mg/m2/dose intravenously over 24 hours for two cycles. The patient's qualityof life improved as noted by a significant decrease in opiate requirements and ability to tolerate oral intake. The drug waswell tolerated with the exception of transient neutropenia.

Periodontitis and Periodontal Drug Delivery Systems: A Review by Mohamed S. Pendekal, Pramod K. Tegginamat (100-112).
Periodontitis is a common disease involving supportive structures of the teeth in all groups, ethnicities, racesand both genders. Targeting to periodontal pocket has made an important contribution to treat periodontitis, but has yetto fully achieve its potential for better treating the periodontal diseases. This review highlights the stages of diseases,etiology and different forms of periodontal diseases for better understanding. This article then proceeds to cover theperiodontal probes, systemic medications and local therapy. Additionally, we focus on the recent advancements of localdrug delivery for treating periodontal diseases.

Serendipity of Erythromycin in the Management of Periprosthetic Inflammation by Weiping Ren, Ralph Blasier, David C. Markel (113-120).
The formation of an inflammatory periprosthetic membrane at the interface of the bone and the prosthesis constitutesa major component of periprosthetic osteolysis and aseptic loosening (AL). Prevention and treatment of periprostheticmembrane inflammation represent a logical approach to prevent this complication of total joint replacement (TJR).Delivering adequate levels of cell-specific therapy to the site of periprosthetic inflammation, without undesirable systemicside effects, present a considerable challenge. Erythromycin (EM), a 14-member lactone ring macrolide antibiotic, hasnovel anti-inflammatory effects at sub-antimicrobial doses through targeting to the NF..B signaling pathway. Thismanuscript describes a unique line of research that investigated the conceptual application of EM to AL/osteolysis fromthe benchtop to a clinical trial. Our previous studies indicated that EM inhibits wear debris- induced inflammation and osteolysis(both in vitro and in vivo). In addition, we found that oral EM treatment (600 mg/day) improved periprosthetic tissueinflammation in a group of AL patients. EM represents a promising drug candidate for AL, because it is immunomodulatory,anabolic, and inhibits osteoclastogenesis. Additional efforts are needed to address some practical issues,including development of quantitative outcome measure(s) for the evaluation of drug efficacy and creation of periprostheticEM delivery devices. If achievable, EM therapy, because of its clinical safety, efficacy, simplicity and goodcompliance, will be a novel option to provide solutions for extending the implant life for those patients who are at a highrisk of AL development.

Management of Painful Symptoms with Duloxetine: A Review of the Efficacy in Pre-Clinical and Clinical Studies by Michael J. Robinson, Jonna Ahl, Adam L. Meyers, Bill H. McCarberg, Smriti Iyengar (121-136).
This is a review of the effect of duloxetine on pain in pre-clinical studies as well as in clinical studies inpatients with diabetic peripheral neuropathic pain (DPNP) and fibromyalgia (FM), and painful symptoms associated withmajor depressive disorder (MDD) and generalized anxiety disorder (GAD). Data sources include the pre-clinical studiesof duloxetine in rodent pain models, and randomized, double-blind, placebo-controlled trials of the efficacy of duloxetine(20-120 mg/day) in the management of chronic pain in DPNP and FM, and in MDD and GAD trials that included painmeasures. In pre-clinical studies, duloxetine reduced pain in animal models of central and neuropathic chronic pain states.In the clinical trials, duloxetine (60-120 mg/day) significantly reduced the severity of pain in patients with DPNP and FM.In pooled analyses of the MDD and GAD studies, there was a significant main effect of treatment with duloxetine onpainful symptoms. The results from these studies demonstrate that duloxetine reduces pain in pre-clinical animal studies,clinical studies of patients with FM and DPNP, and in painful symptoms associated with MDD and GAD.

Pulmonary Drug Delivery System: A Novel Approach for Drug Delivery by Anupama Singh, Rishabha Malviya, Pramod K. Sharma (137-151).
In present study authors review all aspects of pulmonary drug delivery system; including need of drug delivery,different approaches for drug delivery and recent advancement in pulmonary drug delivery system. Review deals withdrug targeting to pulmonary region for the treatment of various diseases such as chronic obstructive pulmonary disease,lung cancer, cystic fibrosis, tuberculosis, asthma, etc. All these disorders are difficult to be effectively cured throughconventional modes of dosage system rather novel delivery systems have been developed which proved to be more sitespecific and less toxic. Apart from various formulations, different delivery devices such as metered dose inhalers (MDI),dry powder inhalers (DPI), nebulizers, aerosolizers, etc. have also improved drug targeting efficacy and reduced dose sizein a more efficient manner. This review contains mainly the tabulated description of different categories of drugs anddevices recently available in the market which makes it easily accessible for the researchers. Proteins, other biologicalsand different marketed products are also successfully available to be delivered through pulmonary route for the betterpatient management. It can be concluded from whole study that different pulmonary delivery system possesses certainspecificity for dosage formulations and serves as an important tool to deliver drugs to the target site.

Advancement in Vaccinology: New Era in Formulation Strategies by Mohammed S. Khan, D.V. Gowda, Hosakote G. Shivakumar (152-159).
The development of vaccines to prevent infectious diseases has been one of the most important contributionsof pharmaceutical sciences. Stemming from the vaccine research and development, not only a large number of diseasespecificvaccines have been developed, but also enormous efforts have been made to improve the effectiveness of vaccinesin order to provide optimal immunization. Understanding the science at a molecular level and related fields providedan opportunity for the development of new vaccines that are based on rational drug design. Introduction of nanotechnologyand the development of nanocarrier-based vaccines have started to receive a lot of attention in order to provide effectiveimmunization through better targeting and by triggering antibody responses at the cellular level. Recent advancesin understanding of the pathogenesis of infectious diseases have opened up doors for newer techniques. The genomicapproach for antigen identification followed by its chemical synthesis has started the trend in genetic immunization. It islikely that vaccinology will greatly benefit from the emerging genomics technologies such as bioinformatics, proteomics,DNA microarray, signature tagged mutagenesis and in-vivo expression technology. This review article is intended tohighlight usefulness of computational techniques in vaccine design, their formulation criteria and describe the past,current and future trends in vaccine development to formulate and deliver these vaccines appropriately to maximize thepotential of modern advances in pathogenesis and vaccinology.