Band 9, Heft 3-4

In this review, we assessed endoscopic imaging using surface-enhanced Raman scattering (SERS). As white-light endoscopy, the current standard for gastrointestinal endoscopy, is limited to morphology, Raman endoscopy using surface-enhanced Raman scattering nanoparticles (SERS endoscopy) was introduced as one of the novel functional modalities. SERS endoscopy has multiplex capability and high sensitivity with low autofluorescence and photobleaching. As a result, multiple molecular characteristics of the lesion can be accurately evaluated in real time while performing endoscopy using SERS probes and appropriate instrumentation. Especially, recently developed dual modality of fluorescence and SERS endoscopy offers easy localization with identification of multiple target molecules. For clinical use of SERS endoscopy in the future, problems of limited field of view and cytotoxicity should be addressed by fusion imaging, topical administration, and non-toxic coating of nanoparticles. We expect SERS endoscopic imaging would be an essential endoscopic technique for diagnosis of cancerous lesions, assessment of resection margins and evaluation of therapeutic responses.

Glucosamine sulfate (GS) has been used orally for the treatment of osteoarthritis (OA). However, it may be susceptible to the liver first pass phenomenon, which greatly affects its bioavailability, in addition to its side effects on the gastrointestinal tract. Alginate nanoparticles (Alg NPs) were investigated as a new drug carrier for transdermal delivery of GS to improve its effectiveness and reduce side effects. GS-Alg NPs were characterized by encapsulation efficiency, NP yield, particle size and surface charge properties. The in vitro release studies of GS and the ex vivo permeability through rat skin were determined using a UV-Vis spectrophotometer. GS-Alg NPs are within the nanometer range of size. High negative surface charge values are obtained and indicate the high suspension stability of the prepared formulation. The in vitro release studies showed that GS is released from Alg NPs in a sustained and prolonged manner. The ex vivo permeability of GS through rat skin is enhanced significantly after encapsulation in the negatively charged Alg NPs. We successfully reported a highly stable nanoparticlulate system using Alg NPs that permits the encapsulation of GS for topical administration, overcoming the disadvantages of oral administration.

The use of miconazole nitrate (MN) in the treatment of oropharyngeal candidiasis (OPC) is limited by low drug bioavailability, frequent administration, fungal resistance and toxicity concerns. Lipid nanogel comprising solid lipid nanoparticles (SLNs) incorporated into a gel base could be employed to prolong and target MN to the oromucosal layers, minimizing its associated side effects while enhancing its lethality against resistant Candida albicans . In this study, novel tailor-made oropharyngeal lipid nanogels encapsulating MN were developed and evaluated for improved treatment of OPC. Wide angle X-ray diffractogram analysis revealed the amorphous nature of the lipid matrix, containing beeswax and Phospholipon ® 90H, used in preparing the SLNs. The SLNs had varied polydispersity indices, good encapsulation efficiency (EE) and mean droplet size of 204.0±2.9–263.0±7.1 nm. The developed lipid nanogels were pseudoplastic and possessed suitable mucoadhesive strengths on ‘cow-everted’ oromucosal tissue, with greater anticandidal properties regarding fungal inhibition than marketed MN formulation (Daktarin ® oral gel) at equivalent concentration. This study has shown that the activity of MN against oral thrush swab (OTS) of C. albicans was improved by formulation as tailor-made mucoadhesive lipid nanogel, and hence could be exploited as an alternative therapeutic carrier for the effective treatment of OPC.

Hepatocellular carcinoma (HCC) results in significantly high mortality rates due to its subtle metastatic expressions. Exorbitant costs of anticancer drugs have lead to the concept of repositioning standard drugs for their anticancer potential. One such antialcoholic drug, disulfiram (DSF), has been reported to show significant cytotoxicity (IC 50 6 μM) against hepatocarcinoma cells. Hence, we studied its antimetastatic and proteasome-inhibiting potential to ascertain its efficacy against metastatic hepatocarcinoma. In addition, we also studied the influence of the components of polysorbate 80-stabilised poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on metastastatic markers and proteasome complexes. A significant reduction in antimigratory assays (0.1 μM) and gelatin zymography (0.5 μM) was observed. A Western blot analysis furthermore confirmed the modulation of metastatic markers. Chymotrypsin-like activity was significantly inhibited at 2 μM of DSF, and in silico docking studies show comparable gliding scores of DSF against standard antimetastatic drugs. Our experiments suggest a significant antimetastatic and proteasome-inhibiting potential of DSF and its loaded NPs. We also infer that polysorbate 80 and PLGA neither show interference with drug behaviour nor inhibit metastasis and proteasome activity, thus behaving as components of a neutral vector. However, they may potentially manipulate the pharmacokinetics of DSF for achieving maximum therapeutic efficacy, in addition to targeted drug delivery.