Current Drug Delivery - Volume 15, Issue 2, 2018

The perpetuation of healthy vision is paramount in an individual. It has been observed that various drug delivery systems have been fabricated to develop vision quality in individuals. Systemic ocular drug therapies have limited efficacy due to poor bioavailability, systemic and toxic side effects and low patient compliance. Various drug systems which follow the ocular route of administration are manufactured to achieve optimized bioavailability along with better patient compliance. Ocular implant is one such example. It is divided into biodegradable and non-biodegradable drug delivery systems wherein the former is more beneficial. This review aims to demonstrate the current momentum in the formulation and optimization of various biodegradable ocular drug delivery systems and its characteristics.

Background: Electrospun nonwoven nanofibers are emerging as a novel carrier for verity of drugs meant for treatment of infections, disorders and tissue engineering scaffolds. These systems may used widely in controlled release of drug that are beneficial for the health management. Nonwoven structures may provide great surface area, absorbable, simplistic processing and economical. For water loving small molecule drugs, their high water solubility and poor partition and compatibility issues with polymers make it long term release yet more challenging. Methods: Several strategies have been explored to control the release of hydrophilic drugs with high drug payload in electrospun fibers. Various techniques like blending, co-axial electrospinning can be used to improve drug payload. Results: Studies have suggested that electrospinning methods are important attributes of developed nanofibers. Further, types of polymers are also important contributory factor on drug load and release. This review gives an overview of nanofibers used for controlled and sustained release for drugs. Conclusions: This articles enlightened that physicochemical and biological properties of nanofibers may be regulated by changing processing and formulation parameters.

Undesirable taste is an important problem for patient compliance. Several oral pharmaceuticals and bulking agents have disagreeable and bitter-tasting components. The Bitter taste characteristics found in such systems have been eliminated or minimized by the development of numerous formulations with improved performance and acceptability especially in children and elderly patient. This review is mainly concerned with the bitter-masking techniques published in peer-reviewed journals and will shed light on different methods of masking undesirable taste of the drugs, and their pharmaceutical applications. Hence, nearly no reference will be made to the techniques published as patent applications.

Background: Management of the health of oral tissues is a prime requirement in dentistry. The prevention of tooth decay and the treatment of lesions and cavities are ongoing challenges. The limitations in dental materials, medications, instruments, procedures put off the accomplishment of this goal. Rationalization of science and technology has made possible to work out these limitations. Nanotechnology which is the outcome of this rationalization has become one of the most favored technologies in medical and dental application. The substantial contribution of nano dental materials is the identification of oral health related problems by better diagnosis and management of dental disorders by bionanomaterials. Conclusion: Application of nanodentistry holds promise for comprehensive dental care by utilizing nanomaterials and ultimately by nanorobots. This review discusses the rationale of nanodentistry, nanocarriers researched in treatment of different dental diseases, the latest innovations in nanomaterials in various disciplines of dentistry; patent literature and related marketed products. Advances in nanotechnology have placed plenty of hopes in terms of improving the oral health care of dental patients.

Background: Inflammation is the key mediator for arthritis. Plant based products are most useful for treating various disorders, but at the same time drug absorption is utmost important for effective therapy. The present aim of our study was to find out the therapeutic concern in pharmacokinetic and pharmacodynamic parameters in an arthritis induced rat model. Methods: Carregenan and complete Freud's adjuvant, both were used for an arthritis induction as an animal model. Formulation of curcumin was prepared in different quality of milk brand, high fat milk with ghee and in an aqueous suspension. They were administered orally to the rats for 21 days continuously. Different pharmacodyanmic parameters were analyzed which include percentage inhibition of inflammation, cytokines (IL-6 and TNF-α), hematological levels, X-Rays and histology condition. Pharmacokinetics was also determined like Cmax, Tmax and Kel using HPLC method. Results: The result concludes that, curcumin in full fat milk with ghee and full fat curcumin formulation treated group showed a higher statistical significant effect in the prevention of inflammation in both the models. The presence of curcumin in plasma was higher only in full fat with ghee formulation and full fat milk formulation treated group when compared to the other groups. Conclusion: Hence, it concludes that the presence of adjuvant act as an enhancer can increase the bioavailability of curcumin for achieving maximum effectiveness.

Background: Lactose intolerance is characterized by the absence of the enzyme lactase (beta-galactosidase) and affects two thirds of the world adult population. Our aim was to evaluate a lactase gastro-resistant formulation to ensure increased activity in the action site of the enzyme (lumen of the small intestine). Simultaneously, we also evaluated the commercial product stability and enzyme activity, because the product containing beta-galactosidase is classified as food supplement according to the Food and Drug Administration (FDA), so it is free to pass quality testing, efficacy and stability. So, it is possible that contain some irregularities as to the content and enzymatic activity. Methods: The dissolution assay was performed using a dissolution test system and commercial product and the gastro-resistant formulation were evaluated according to a method adapted to the conditions recommended by United States Pharmacopeia (US Pharmacopeia) for gastro-resistant formulations. For the assessment of enzymatic activity throughout the dissolution test was employed the official method of lactase assay described in US Pharmacopoeia. This method is based on a colorimetric reaction which the substrate reacts with the enzyme generate a colored product further analyzed by UVVisible spectrophotometry. Results: When carrying out dissolution test in commercial product it is noted that the existing formulation is not able to protect the enzyme from degrading action of gastric environment (a loss of 86.0 ± 0.8% of lactase activity was observed). Our proposed gastro-resistant pharmaceutical form there was no loss of activity during the acid step and the end of the dissolution test the found activity was 95 ± 1.3%. Conclusion: The formulations proposed in this work using hypromellose capsules ensure the enzymatic activity of lactase, preventing its contact with the acid medium. For the other side, the results of commercial tablets for lactase release indicate a significant loss of enzyme activity due to the immediate release of the enzyme in the simulated gastric fluids.

Background: Fluoroquinolones, the synthetic antibacterial agents are being successfully utilized against bacterial infections, since the time immemorial. Despite of enormous useful features, these drugs are associated with some limitations also. Large number of efforts has been made by various scientists to improve pharmacokinetic properties of these drugs and hence, to overcome the limitations associated with them. Objectives: The aim of this paper is to introduce a novel scheme for synthesis of prodrug with improved pharmacokinetic properties i.e., lipophilicity and consequently, modified bioavailability of norfloxacin. Methods: Fatty acid hydrazide of selected fatty acid was synthesized followed by preparation of 5-formyl salicylamide. N-Mannich base of norfloxacin was synthesized by reacting norfloxacin with 5-formyl salicylamide. The prodrug was obtained by covalently coupling this N-Mannich base of norfloxacin with fatty acid hydrazide. The synthesized lipid based prodrug was evaluated for partition coefficient by shake flask method and screened for antimicrobial activity against selected strains. Drug content determination and in vitro dissolution studies utilizing HPLC were also carried out. Results: The synthesized prodrug was found to exhibit improved partition coefficient (1.15) when compared with parent drug, norfloxacin (0.46). The results of antimicrobial evaluation indicate promising antibacterial and antifungal activity. Conclusion: The synthesized prodrug proved to be a good antimicrobial substance due to improved lipophilicity and would be expected to be used as a suitable candidate for exploration of possible utilities in treatment of bacterial infections in forthcoming time.

Background: The combination of medicinal plants and polymeric matrices raised the possibility of obtaining new drugs to treat a number of diseases, including cancer. Breast cancer is one of the most frequent diseases among women, but the effective treatments is still a challenge. Methods: Thus, this study investigated the effect of herbal mixture adsorbed to PEG microspheres on MCF-7 human breast cancer cells and these cells in co-culture of blood MN cells. The MCF-7 cells and the blood mononuclear [MN] cells from volunteer donors. MN cells, MCF-7 cells and co-culture [MN and MCF-7 cells] were pre-incubated for 24 h with or without herbal mixture [HM], polyethylene glycol [PEG] microspheres or herbal mixture adsorbed in PEG microspheres [PEG-HM]. Viability, intracellular calcium and apoptosis were determined by flow cytometry. The herbal mixture adsorbed in PEG microspheres reduces the viability of MCF-7 cells. Results: The lowest viability índex was observed in co-culture incubated with herbal mixture adsorbed to PEG microspheres. MN cells, MCF-7 cells and co-culture showed higher intracellular Ca2+ release when incubated with herbal mixture adsorbed to PEG microspheres. The apoptosis index was higher in MCF-7 cells that were treated with herbal mixture. The highest apoptosis index was observed in coculture of these cells incubated with herbal mixture adsorbed to PEG microspheres. Conclusion: These data suggest that herbal mixture adsorbed by PEG microspheres has apoptotic effects on human MCF-7 breast cancer cells and is therefore a possible therapeutic alternative.

Background: Chemotherapy still encounters a serious drawback, the lack of selectivity of anticancer drugs toward neoplastic cells, thus, the normal cells are affected by the cytotoxic action of the drugs. This causes a narrow therapeutic index in most anticancer drugs. Objective: We describe the preparation of pullulan-tocopherol succinate-folic acid (Pu-TS-FA) micelles for the first time to targeted delivery of Epirubicin (EPI) to Hela and MCF-7 cell lines. Methods: We confirmed the structure of conjugate using spectroscopic methods. The degree of substitution for both folic acid and tocopherol succinate was calculated using 1HNMR. We prepared the micelles via direct dissolution method. All the physicochemical properties of micelles including size, zeta potential, polydispersity index (PDI), critical micelle concentration (CMC), entrapment efficiency (EE %) and release efficiency (RE24%) were determined. The morphology of particles was studied using transmission electron microscopy (TEM), and the in-vitro cell cytotoxicity of EPI loaded micelles was studied using MTT assay on MCF-7 and Hela cell lines. Results: The optimized micelles showed the particle size of 149.5 nm, the zeta potential of -6.49 mV, a polydispersity index of 0.259 ± 0.07, LE% of 88 %, and RE24% of 63 ± 2.45 % with a relatively low CMC 194.87 μg/ml. TEM showed the relatively uniform spherical structure for particles and in vitro MTT assay showed that EPI loaded micelles were more toxic on Hela cell line than MCF7 as expected. Conclusion: Since the Pu-TS-FA micelle could improve the anticancer activity of epirubicin and would be a promising candidate for EPI treatment of cancers.

Background: Due to its excellent adsorption capability, activated carbon(AC) has also been employed as a drug carrier. However, applications of the AC carrier in traditional Chinese medicine (TCM) have been rare. We selected the Eucommia ulmoides leaf extract as the drug of choice and AC as its carrier, to investigate the adsorption and sustained release behavior of the Eucommia ulmoides leaf extract on the AC. Methods: AC was employed in this study as the sustained release carrier and its capability for adsorption and sustained release of Eucommia ulmoides leaf extracts was systematically investigated. Acid or alkali modified AC was assessed for its ability to absorb and sustain release of Eucommia ulmoides leaf extracts according to a variety of adsorption/release rate and composition. Results: Results demonstrated that the adsorption rate for the differently modified AC reached above 80 %, whereas the adsorption of Eucommia ulmoides leaf extracts on the AC was selective. The composition of the sustained release liquid, which was treated by the acid modified AC, was almost similar to the original extract. The acid modified AC was therefore taken as an optimal carrier that can be used for Eucommia ulmoides leaf extracts sustained release. Conclusion: The synchronous release and absorption of different ingredients in the active ingredient release process ensures the global and cooperative effect with sustained and less toxic advantages. The ideal synchronous release is that the absorbed component proportion is consistent with its release. The acid modified AC was therefore taken as the optimal carrier that can be used for Eucommia ulmoides leaf extracts sustained release.

Background: Resveratrol is a polyphenol that has gained momentum in therapeutics in the last few years. Objective: In this study, we hypothesised that resveratrol could act prophylactically and/or treat inflammatory lesions of the oral cavity after being delivered by two different formulations of buccal mucoadhesive tablets (F1 and F2, which differed in terms of viscosity agents used). Methods: This hypothesis was assessed through permeation studies, to verify diffusion of the drug through the buccal mucosa using a porcine model to predict human in vivo behaviour. Results: F2 (tablet with less viscosity agent) presented better permeation than F1, but the amount of drug that crossed the mucosa was still low compared to the amount retained within it (35.90 μg found in the receptor medium and 15.63 mg quantified within the mucosa). Conclusion: This accounted for a local effect rather than a systemic one, which is desirable for local processes, such as oral mucositis, lichen planus, erythema multiforme, nicotinic stomatitis, recurrent aphthous stomatitis, among others. In this sense, resveratrol-loaded mucoadhesive tablets appear to be a prominent alternative to prevent and/or cure inflammatory lesions of the oral cavity.

Background: Niosomes are non-ionic surfactant vesicles used as drug carriers for encapsulating both hydrophobic and hydrophilic drugs. The aim of the present study was to prepare and characterize niosomes formulations for oral delivery of telmisartan and evaluated for its antihypertensive activity. Method: Telmisartan loaded niosomes were prepared using thin film hydration method by varying the Span 60 and cholesterol at several molar ratios and characterized for vesicles size, polydispersity index, zeta potential, entrapment efficiency. The in vivo antihypertensive study of optimized formulation and molecular impact of angiotensin II type-1 receptor (AT1R) messenger Ribonucleic acid (mRNA) and protein expression on smooth vascular muscles of aorta was determined by real-time polymerase chain reaction (RT-PCR) and western blot analysis in Wistar albino rats. Results: The optimized niosomes formulation NS6 presented vesicles size of 618.47 nm, polydispersity index of 0.86, with entrapment efficiency of 83.83% and possesses negative charge. In vivo study showed that the optimized formulation could reduce the systolic blood pressure in methyl prednisolone acetate induced hypertensive rats in close proximity to normal range of systolic blood pressure and maintain it over an extended period. In addition, telmisartan loaded niosomes treatment to hypertensive rats significantly attenuates the raised mRNA level and protein level of AT1R gene in comparison to hypertensive rats. Conclusion: Results of present study confer the potential of developed niosomes as suitable carriers for improved oral delivery of telmisartan.

Context: Oral disintegrating tablets (ODTs) represent a better option than conventional tablets for geriatric population, owing to their fast onset of action and their better patient compliance. Objective: Two principal therapeutic high-dose nutraceuticals; chondroitin sulphate and glucosamine were formulated into an oral disintegration tablet (ODT) intended for sublingual administration, and optimized to improve compliance and achieve rapid onset of action in osteoarthritis treatment. Materials and Methods: Different formulations were prepared either by melt granulation or direct compression techniques. Excipients at different ratios such as superdisintegrants, pharmaburst™ C1, spray-dried mannitol, and polyethylene glycols were used to enhance the disintegration time for the ODT systems. Results: Although the ODT systems weighed around 1.3 gm with 60% drug load, some systems disintegrated within 2-3 min with 100% drug release. Pharmaburst™ C1 turned out to be the key excipient responsible for the superdisintegration properties of the ODTs. Dissolution enhancement of the two nutraceuticals could be achieved compared to the marketed conventional tablets. Conclusion: The improved disintegration and dissolution properties of our prepared ODTs are expected to enhance the bioavailability of the high dose glucosamine and chondroitin sulphate in comparison with conventional tablets, which delineates them as a promising dosage form for the aforementioned nutraceuticals.

Background: The use of chemotherapy drug is hindered by relatively low selectivity toward cancer cells and severe side effects from uptake by noncancerous cells and tissue. Thus, targeted drug delivery systems are preferred to increase the efficiency of drug delivery to specific tissues as well as to decrease its side effects. The aims of this paper are develop microwave-triggered controlled-release drug delivery systems using porous γ-Fe2O3@mWO3 multifunctional core-shell nanoparticles. We also studied its magnetic- microwave to heat responsive properties and large specific surface area. We chose ibuprofen (IBU) as a model drug to evaluate the loading and release function of the γ- Fe2O3@mWO3 nanoparticles. Methods: We used a direct precipitation method and thermal decomposition of CTAB template method to synthesize core-shell structured γ-Fe2O3@mWO3 nanoparticles. The specific surface areas were calculated by the Brunauer-Emmett-Teller (BET) method. The load drug and controlled release of the γ-Fe2O3@mWO3 triggered by microwave was determined with ultraviolet-visible spectroscopic analysis. Results: The γ-Fe2O3@mWO3 nanoparticles possesses high surface area of 100.09 m2/g, provides large accessible pore diameter of 6.0 nm for adsorption of drug molecules, high magnetization saturation value of 43.6 emu/g for drug targeting under foreign magnetic fields, quickly convert electromagnetic energy into thermal energy for controlled release by microwave-triggered which was caused by mWO3 shell. The IBU release of over 78% under microwave discontinuous irradiation out classes the 0.15% within 20s only stirring release. This multifunctional material shows good performance for targeting delivery and mWO3 microwave controlled release of anticancer drugs based on all the properties they possess. Conclusion: The porous shell and the introduction of absorbing material not only increased the drug loading efficiency of the nanoparticles but also realized the microwave-stimulated anticancer drug controlled release. The nanoparticles would be very promising for microwave-induced controlled drug release, targeted drug delivery and hyperthermia therapy using microwave.

Background: The anti-cancer potential of curcumin, a natural NFΚβ inhibitor, has been reported extensively in breast, lung and other cancers. In vitro and in vivo studies indicate that the therapeutic efficacy of curcumin is enhanced when formulated in a nanoparticulate carrier. However, the mechanism of action of curcumin at the molecular level in the hypoxic tumour micro-environment is not fully understood. Hence, the aim of our study was to investigate the mechanism of action of curcumin formulated as nanoparticles in in vitro models of breast and lung cancer under an hypoxic microenvironment. Methods: Biodegradable poly(lactic-co-glycolic acid) PLGA nanoparticles (NP), loaded with curcumin (cur-PLGA-NP), were fabricated using a solvent evaporation technique to overcome solubility issues and to facilitate intracellular curcumin delivery. Cytotoxicity of free curcumin and cur-PLGA-NP was evaluated in MDA-MB-231 and A549 cell lines using migration, invasion and colony formation assays. All treatments were performed under an hypoxic micro-environment and whole cell lysates from controls and test groups were used to determine the expression of HIF-1α and p65 levels using ELISA assays. Results: A ten-fold increase in solubility, three-fold increase in anti-cancer activity and a significant reduction in the levels of cellular HIF-1α and nuclear p65 (Rel A) were observed for cur-PLGA-NP, when compared to free curcumin. Conclusion: Our findings indicate that curcumin can effectively lower the elevated levels of HIF-1α and nuclear p65 (Rel A) in breast and lung cancer cells under an hypoxic tumour micro-environment when delivered in nanoparticulate form. This applied means of colloidal delivery could explain the improved anti-cancer efficacy of curcumin and has further potential applications in enhancing the activity of anti-cancer agents of low solubility.