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The present study aimed to develop topical combinatorial therapy of nisin and 5-fluorouracil in a single nanosized formulation against skin cancer. Nisin and 5-fluorouracil were encapsulated in an organogel system (NF-OG) and investigated for morphology, physicochemical properties, cytotoxicity, encapsulation and release. NF-OG was evaluated against DMBA/TPA murine skin cancer in terms of tumour statistics, histoarchitecture, TUNEL and M1/M2 macrophages. The optimised NF-OG formulation exhibited particle size of 185.1 ± 11.24 nm, zeta potential of −7.93 ± 0.60 mV, offered substantial drug loading and temporal release. NF-OG therapy led to improved cytotoxicity of nisin and 5-FU against B16-F10 cells, significant decrease in tumour volume (84.983 mm3) in treated group as compared to untreated group (490.482 mm3) accompanied by restoration of histoarchitecture and repolarization of macrophages. The study yielded a promising delivery system exhibiting potent anticancer activity and forms the bases for further applications in clinical settings. [ABSTRACT FROM AUTHOR]

In modern world, Pharma sector observes steep increase in demand of personalized medicine. Various unique ideas and technology were proposed and implemented by different researchers to prepare personalized medicine and devices. 3-dimensional printing (3DP) is one of the revolutionary technologies which can be used to prepare tailored medicine via CAD (Computer Aided Design) software. 3DP allows researchers to manufacture customized dosage form with desired modifications in geometry which would in turn alter dosage behaviour of the product with reduced side effects. Current achievement of 3DP includes personalized and adjustable dosage form, multifunction drug delivery systems, medical devices, phantoms, and implants specific to patient anatomy. Additionally, 3DP is employed for preparing tailored regenerative medicines. This review focuses on 3DP use in pharmaceuticals including drug delivery systems and medical devices with their method of fabrication. Additionally, different clinical trials as well as different patents done till date are cited in the paper. Furthermore, regulatory issues and future perspective related to 3 D printing is also well discussed. [ABSTRACT FROM AUTHOR]

Due to changed lifestyle and other reasons, diabetes has become one of the common metabolic disorder of the globe. Numerous therapeutic options are available, which controls the plasma glucose levels. However, most of the drugs are associated with some undesired side effects. Owing to the side effects and enhanced understanding of the phytochemicals, an inclination toward herbal medicine is seen in the population. These herbal products are also associated with concerns like poor aqueous solubility, compromised permeation, and a low degree of bioavailability. So, the emergence of nanotechnology in the herbal medicine is required to nullify the associated concerns of conventional antidiabetic drugs. The present review aims to compile the literature available for the nano-interventions pertinent to herbal products for diabetes management. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to formulate nanostructured lipid carriers (NLCs) of dithranol-loaded in gel for ease of application and to evaluate its anti-psoriatic efficacy vis-a-vis conventional ointment formulation. Significance: This study will provide an insight about the use of nanocarriers, esp. NLCs loaded with dithranol for the effective treatment of psoriasis. Methods: Dithranol-loaded NLCs were prepared by hot melt homogenization method and characterized for particle size and percentage entrapment efficiency. The optimized NLCs were loaded into gel and evaluated for drug release, spreadability, rheological behavior, and staining. Anti-psoriatic efficacy of the NLC gel was evaluated in imiquimod (IMQ) induced psoriatic plaque model in comparison with prepared conventional ointment formulation (1.15% w/w dithranol). Results: NLCs were prepared with particle size below 300 nm, polydispersity index (PDI) below 0.3 and percentage entrapment efficiency of ∼100%. The prepared NLC gel was then compared with the ointment for drug release, staining property, and efficacy. Topical application of dithranol-loaded NLC gel on IMQ-induced psoriatic plaque model reduced the symptoms of psoriasis assessed by both Psoriasis area severity index (PASI) scoring and enzyme-linked immunosorbent assay. There was a significant reduction in disease severity and cytokines like Interleukins-17, 22, 23 and Tumor necrosis factor-α by the developed system in comparison to the negative control. Conclusions: To conclude dithranol-loaded NLCs in gel base was efficacious in management of psoriasis at the same drug concentration and also offer less cloth staining to that of the ointment product. [ABSTRACT FROM AUTHOR]

The objective of the present study was to deliver docetaxel to cancerous cells with enhanced efficacy and safety profile, using aspartic acid linked fullerenols. This aspartic acid derivatized fullerenol conjugate linked with docetaxel was characterized by UV, FT-IR and NMR spectroscopy. Studies for particle size, PDI, zeta potential and FE-SEM were also performed. The conjugate was evaluated for release kinetics, cancer cell cytotoxicity, cellular uptake using confocal laser microscopy and also for pharmacokinetic profile. Cytotoxic studies proved that there was almost 4.3 folds decrease in IC50 with significantly enhanced cellular uptake of the nanometric conjugates. It was observed that the bioavailability was enhanced by 5.8 folds when compared to that of pure DTX. The developed nanoconstructs were erythrocyte compatible and offered decreased protein binding. The findings are encouraging and offer a novel carrier with enhanced efficacy and safety of a drug, belonging to BCS class IV. [ABSTRACT FROM AUTHOR]

Context: Aceclofenac (ACE) is a systematically designed drug, developed to circumvent the concerns associated with diclofenac. But ACE is also associated with non-steroidal anti-inflammatory drug (NSAIDs)-tagged side effects, although of decreased amplitude. Objective: The present study aims to develop phospholipid-based vesicles (elastic membrane vesicles; EMV and ethosomes) loaded with ACE and explore their potential in topical delivery. Methods: Elastic membrane vesicles (EMVs) were prepared by thin-film hydration method and ethosomes by cold method. The composition of both the vesicular systems was selected on the basis of vesicle density and drug entrapment. The developed systems were characterized for micromeritics, surface charge, drug entrapment, and morphology. Ex vivo permeation and retention studies on Laca mice skin were performed. In vivo pharmacodynamic evaluation was performed by tail-flick method and carrageenan-induced rat paw-edema model. During stability studies, percent drug leakage was studied. Results: The selected ratios of phospholpid:drug:stearylamine for EMVs and ethosomes were 8:1:1 and 3:1:1, respectively. The ethosomes were found to offer more vesicle density, drug loading, and deformability index as compared with that of EMVs. The drug permeation and the retention offered by both the vesicular systems were superior to that of the conventional cream; however, performance of ethosomes superseded that of EMVs. The phospholipid-based vesicles were found to be well tolerated on mice skin. Although, the in vivo performance of ethosomes was found to be better than that of EMVs in both the studied models. Conclusion: The phospholipid-based vesicular systems, especially, ethosomes can be a promising tool to enhance the delivery and safety of ACE by topical route. [ABSTRACT FROM AUTHOR]

Chronic plaque psoriasis is an inflammatory skin disease affecting 2–3% of the world population. With increasing understanding of the progress of disease and its causes, bacterial infection is reported to be one of the potential reasons. In this regard, fusidic acid (FA), a steroidal antibiotic, has been a drug of choice which could play an important role by virtue of its unique mechanism of action. Despite many topical formulations of FA in practice, drug-delivery issues like permeability in the prevailing infectious conditions and stability of the drug are yet the challenges not been covered so far from the formulation development perspective. For these issues, liposomes, on account of their carrier-specific properties, have been suggested as delivery tools to fulfill the expectations. In the present work, FA liposomes (FA-LP) were prepared and characterized for its varied traits such as size (420–740 nm), surface charge, morphology, percent skin permeation (>75%), and retention (1.620 ± 0.8 mg/cm2). Confocal laser scanning microscope (CLSM) images revealed appreciable cell-uptake of fluorescent dye-loaded liposomes. In stability, FA-LP proved to be stable with respect to drug leakage and vesicle size.In vivostudies using the mouse tail model, FA-LP, are found significantly better (p < 0.05) vis-à-vis conventional one with improved efficacy in and around the target site by the carrier-effect. Hence, the work suggests for the possibility of a better FA liposome-based formulation as a potential option in addressing the infectious challenges of psoriasis. [ABSTRACT FROM PUBLISHER]

Topical delivery of local anesthetics has been an area of interest for researchers considering the barrier properties of skin and unfavorable physicochemical properties of drugs. In the present study, efforts have been made to modify thein vivoefficacy of eutectic mixture of lidocaine and prilocaine by exploiting the phospholipid modified microemulsion based delivery systems. The strategic QbD (D-optimal mixture design) enabled systematic optimization approach, after having obtained the isotropic area of interest by ternary phase diagram, has resulted into the system with most desirable attributes. Latter include nano-scale, globular structures with an average size of 40.6 nm, as characterized by TEM and DLS. The optimized microemulsion systems in gel dosage forms revealed the better permeability over commercial cream (CC) through abdominal rat skin. Enhancement in the flux from MOPT-NMPgel was 3.22-folds for prilocaine and 4.94-folds for lidocaine, in comparison to that of CC. This enhanced skin permeability is very well reflected in thein vivostudies, wherein intensity and duration of action was augmented significantly. The skin compliance of the optimized formulation was revealed in histopathological studies. The overall benefit relating to efficacy and safety-compliance could be correlated to the uniqueness of the carriers, composed of phospholipids and other components. Hence, the developed phospholipid-microemulsion based gel formulation has been proposed as more useful alternative for the topical delivery of lidocaine and prilocaine. [ABSTRACT FROM AUTHOR]

Capsaicin (CP), a recent FDA-approved drug for the topical treatment of neuropathic pain, is associated with several side effects like irritation, burning sensation, and erythema, resulting in poor patient compliance. The present study is an attempt to study the effect of CP encasement in nano-lipoidal carriers (NLCs) on skin-transport characteristics, in vivo pharmacological performance, skin compliance, and stability of the finished product. The study also compares two methods of NLC preparation, namely micro-emulsification and rotary-evaporation for various attributes. The results demonstrated that micro-emulsion technique produced smaller nanoparticles vis-à-vis the rotary-evaporation method. Out of the various studied solid lipids, NLCs from stearic acid offered smallest size and the highest negative zeta potential. The NLC-gel offered higher skin permeation and skin retention of CP across LACA mice skin as compared with the conventional cream. The analgesic effect was observed to be enhanced substantially than that of the conventional cream when tested on a radiant mouse tail-flick model. The most alarming problems of skin-irritation and redness were successfully taken care by NLC-gel while the mice group receiving conventional cream showed marked changes in the skin histopathology. Besides the enhanced efficacy and decreased skin-irritation, the developed CP-NLCs also found to be stable and Theologically accepted formulation for the treatment of pain-associated disorders. [ABSTRACT FROM AUTHOR]

Objective: Tamoxifen (TAM) is widely employed in the treatment of breast malignancies and is also found to be effective in psoriasis treatment. The current studies aimed to explore the antipsoriatic potential of topical TAM encapsulated in the new generation phospholipid-based vesicular and micellar systems, i.e. flexible membrane vesicles (FMVs) and pluronic lecithinized organogels (PLOs). Methods: TAM-loaded-FMVs were prepared by thin-film hydration technique, while TAM-PLOs were prepared by simple mixing. Mouse-tail model was used to evaluate the antipsoriatic activity of the novel formulations. The mouse tails were treated once-a-day with different formulations for a period of four weeks and prepared for longitudinal histological sections by hematoxylin-eosin staining technique. The length of the orthokeratotic regions in stratum granulosum was measured on 10 sequential scales per tail section as percentage of the full length of the scale, and the drug activity was calculated further. Results: Evaluation of antipsoriatic activity on mice tail revealed significantly higher ( p < 0.01) efficacy of TAM-FMV gel (i.e. 35.8%) and TAM-PLO (i.e. 24.6%) vis-à-vis the conventional TAM-hydrogel (i.e. 10.2%). Conclusions: The results of these studies demonstrated immense potential of the topically applied TAM-encapsulated vesicular and micellar systems in psoriasis, thus calling for more comprehensive investigations to establish the role of TAM in the management of psoriasis. [ABSTRACT FROM AUTHOR]

Background: Treatment of photoaging includes non-prescription cosmeceuticals and prescription products, retinoids. Isotretinoin, an established anti-acne retinoid, is also reported to delay the aging process. However, the drug is reported to be an irritant on skin. Purpose: The present study endeavors to explore the potential of a novel set of biocompatible nano-structured systems of isotretinoin in the treatment of photoaging. Methods: Nano-lipoidal carriers (NLCs) of isotretinoin were developed, characterized and investigated in vivo for anti-aging potential in Laca mice vis-à-vis the marketed products of retinoids. The anti-aging efficacy of NLCs was measured in terms of visual and redox-biochemical parameters in ultraviolet (UV)-irradiated mice. Results: Visual observations revealed that there was no significant change ( p < 0.05) w.r.t. erythema, skin sagging and wrinkles in the skin of the animals treated with NLCs formulation compared to the marketed product(s). The malondialdehyde levels were found to be significantly reduced, whereas glutathione levels were increased with the application of NLCs vis-à-vis control and test formulations. The NLCs were able to maintain the normal redox-balance of UV-irradiated skin, and were better tolerated by the animals. Conclusion: The study ratifies enhancement in the efficacy of isotretinoin against photoaging and improved skin biocompatibility after its encasement in novel topical dosage forms. [ABSTRACT FROM AUTHOR]

Despite marked antipsoriatic activity of dithranol (anthralin), the drug is quite infrequently employed in therapeutic practice owing to its strong propensity to cause skin problems like irritation, erythema and peeling, and potential formulation problems like photolability and high lipophilicity. Accordingly, it was planned to systematically formulate optimized dithranol-loaded emulsomes with enhanced biocompatibility, efficacy and stability. Emulsomes were prepared by a thin film hydration technique and optimized for composition using formulation by design (FbD). The optimized dithranol-loaded emulsomes were found to substantially enhance the antipsoriatic activity on a mouse-tail model vis-à-vis marketed product. Also, the selected composition offered enhanced drug permeation and marked skin retention. The formulation was found to be quite non-irritant, stable and biocompatible in comparison to the marketed product. The present findings establish the usefulness of lipid-based colloidal carriers to increase the stability, and enhance the efficacy and patient compliance of an age-old irritant dithranol. [ABSTRACT FROM AUTHOR]

Purpose: Tamoxifen (TAM) is a non-steroidal estrogen receptor modulator known for its anticancer activity. Apart from marked breast cancer activity, this drug has also shown potential in treating other types of cancers including skin cancers. TAM is reported to be associated with serious side effects primarily due to its systemic distribution. The localized delivery of this drug in this regard would be highly beneficial with respect to safety as well as efficacy. Methods: In the current studies, an endeavor has been made to investigate the efficacy of topically applied liposome-encapsulated TAM on skin cancer model. The drug was encapsulated in phospholipid-based vesicular systems viz. conventional liposomes and elastic liposomes. Incidence of papillomas and histopathological examination were employed to determine the efficacy of the tested formulations. Results: The results demonstrated carrier-dependent strong inhibition of skin carcinogenesis with encapsulated drug vis-à-vis drug in the solution form. The encouraging findings from the current work construe immense potential of the TAM-loaded liposomal systems in the management of skin cancer. [ABSTRACT FROM AUTHOR]

Capsaicin, extracted from the fruits of Capsicum, is a powerful local stimulant with strong rubifacient action, devoid of vesication. Topical use of capsaicin is quite common in the treatment of various pain-associated musculo-skeletal disorders, itching and neuropathy. Despite its high pharmacodynamic potential, the patient compliance to the drug is reported to be poor owing to multiple skin problems like irritation, burning sensation, and erythma. The present study targets the encasement of drug in the interiors of flexible membrane vesicles (FMVs), as these are reported to have better penetration in the deeper layers of skin, thus leading to enhanced localization of drug and consequently, decreased skin irritation. Multilamellar drug-loaded FMVs, prepared by thin-film hydration were evaluated for their efficacy in vitro and in vivo. When compared with conventional liposomes, the formulated FMVs showed higher skin retention during ex vivo permeation studies employing LACA mice skin, higher analgesic potential using radiant tail-flick method in mice, and better flexibility in regaining their size. Being less of an irritant, these vesicular carriers were also found to be more comfortable on human skin. Thus, the capsaicin-loaded FMVs offer high potential as topical drug delivery technologies with improved patient acceptance and effectiveness. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop and characterize a novel dithranol-containing phospholipid microemulsion systems for enhanced skin permeation and retention. Based on the solubility of dithranol, the selected oils were isopropyl myristate (IPM) and tocopherol acetate (TA), and the surfactants were Tween 80 (T80) and Tween 20 (T20). The ratios of cosurfactants comprising of phospholipids and ethanol (1 : 10) and surfactant to co-surfactant (1 : 1 and 2.75 : 1) were fixed for the phase diagram construction. Selected microemulsions were evaluated for globule size, zeta potential, viscosity, refractive index, per cent transmittance, stability (freeze thaw and centrifugation), ex vivo skin permeation and retention. The microemulsion systems composed of IPM and T80 with mean particle diameter of 72.8 nm showed maximum skin permeation (82.23%%), skin permeation flux (0.281 mg/cm2/h) along with skin retention (8.31%%) vis-àà-vis systems containing TA and T20. The results suggest that the developed novel lecithinized microemulsion systems have a promising potential for the improved topical delivery of dithranol. [ABSTRACT FROM AUTHOR]