Liposomal drug delivery: a versatile platform for challenging clinical applications.

Liposomes are lipid based vesicular systems that offer novel platform for versatile drug delivery to target cell. Liposomes were first reported by Bangham and his co-workers in 1964 (1). Since then, liposomes have undergone extensive research with the prime aim to optimize encapsulation, stability, circulation time and target specific drug delivery. Manipulation of a liposome's lipid bilayer and surface decoration with selective ligands has transformed conventional liposomes into adaptable and multifunctional liposomes. Development of liposomes with target specificity provide the prospect of safe and effective therapy for challenging clinical applications. Bioresponsive liposomes offer the opportunity to release payload in response to tissue specific microenvironment. Incorporation of novel natural and synthetic materials has extended their application from stable formulations to controlled release targeted drug delivery systems. Integration and optimization of multiple features into one system revolutionized research in the field of cancer, gene therapy, immunotherapy and infectious diseases. After 50 years since the first publication, this review is aimed to highlight next generation of liposomes, their preparation methods and progress in clinical applications.

Development, characterization, and clinical investigation of Spinacia oleracea-based ultra-high pressure homogenized emulsion system for facial physiological parameters.

BACKGROUND: Spinacia oleracea (SO) exhibits radical scavenging and tyrosinase inhibition activity indicating potential as a depigmenting agent. AIMS: To develop and characterize a stable emulsified system containing SO extract through ultra-high pressure homogenization, evaluate skin permeability, and enumerate in vivo performance in terms of melanin index, skin spots analysis, and related skin physiological parameters. METHOD: Free radical scavenging and tyrosinase inhibition potential of SO extract was quantified through DPPH radical scavenging and mushroom tyrosinase inhibition assay, respectively. Six SO extract loaded ultra-high pressure emulsified systems (UHSO) were developed using ultra-high pressure homogenizer and assessed for size and polydispersity index (PDI). Among the prepared formulations, the optimized formulation (UHSO6) was subjected to 90 days stability studies performed at 8°C, 25°C, 40°C, and 40°C+75% RH (relative humidity) for organoleptic features, pH, and rheology. Ex vivo skin permeability studies were performed on abdominal skin from male albino rat. Changes in skin physiological parameters were evaluated in healthy female volunteers (n = 13) for 12 weeks utilizing mexameter® , corneometer® , and sebumeter® . Skin spots were analyzed through computerized analysis of high-resolution images by visioFace® . RESULTS: SO extract exhibited promising antioxidant (88±0.0096%) and tyrosinase inhibition potential (90.6 ± 0.0015 mg of Kojic Acid Eq/g of extract). Optimized UHSO was found to be stable with respect to stability evaluation, globule size (1110 nm), zeta potential (-27.6), and PDI (0.34). Ex vivo skin permeation of UHSO was significantly higher than SO loaded coarse emulsion. Moreover, the formulation showed a significant decrease in skin melanin, spot count, and spot % area, whereas skin hydration index was improved significantly. CONCLUSION: Stable SO extract loaded emulsion system was successfully developed by a novel, cost-effective technique of ultra-high pressure homogenization which showed improved performance in terms of skin permeation and other skin physiological parameters.

Nanostructured Ethosomal Gel Loaded with Arctostaphylosuva-Ursi Extract; In-Vitro/In-Vivo Evaluation as a Cosmeceutical Product for Skin Rejuvenation.

BACKGROUND: Arctostaphylosuva-ursi(AUU) being rich in polyphenols and arbutin is known to have promising biological activities and can be a potential candidate as a cosmaceutical. Ethosomes encourage the formation of lamellar-shaped vesicles with improved solubility and entrapment of many drugs including plant extracts. OBJECTIVE: The objective of this work was to develop an optimized nanostructured ethosomal gel formulation loaded with AUU extract and evaluated for skin rejuvenation and depigmentation. METHODS: AUU extract was tested for phenolic and flavonoid content, radical scavenging potential, reducing power activity, and in-vitro SPF (sun protection factor) estimation. AUU loaded 12 formulations were prepared and characterized by SEM (Scanning Electron Microscopy), vesicular size, zeta potential, and Entrapment Efficiency (%EE). The optimized formulation was subjected to noninvasive in-vivo investigations after incorporating it into the gel system and ensuring its stability and skin permeation. RESULTS: Ethosomal vesicles were spherical in shape and Zeta size, zeta potential, PDI (Polydispersity Index), percentages of EE and in-vitro skin permeation of optimized formulation (F3) were found to be 114.7nm, -18.9mV, 0.492, 97.51±0.023%, and 79.88±0.013% respectively. AUU loaded ethosomal gel formulation was stable physicochemically and exhibited non-Newtonian behavior rheologically. Moreover, it significantly reduced skin erythema, melanin as well as sebum level and improved skin hydration and elasticity. CONCLUSION: A stable AUU based ethosomal gel formulation could be a better vehicle for phytoextracts than conventional formulations for cosmeceutical applications such as for skin rejuvenation and depigmentation.

Development of Niacinamide/Ferulic Acid-Loaded Multiple Emulsion and Its In Vitro/In Vivo Investigation as a Cosmeceutical Product.

Objective: Multiple emulsions have the ability to incorporate both lipophilic and hydrophilic actives in the same preparation and facilitate permeation of active ingredients through skin. The current study was aimed at formulating niacinamide/ferulic acid-loaded stable multiple emulsion (MNF) and its in vitro/in vivo characterization as a cosmeceutical product. Methods: Both the compounds were evaluated for their radical scavenging potential by the DPPH method and FTIR analysis. Then, placebo and active formulations were prepared using a double emulsification method and were investigated for stability testing (changes in color, odor, and liquefaction on centrifugation, pH, and globule size) for a period of three months. Afterwards, MNF was investigated for in vitro sun protection factor, rheological studies, entrapment efficiency, zeta potential, zeta size, and ex vivo permeation. Moreover, after ensuring the hypoallergenicity and safety, it was also checked for its cosmeceutical effects on human skin using noninvasive biophysical probes in comparison with placebo. Results: Results demonstrated that MNF showed a non-Newtonian behavior rheologically and both MNF and placebo were stable at different storage conditions. Entrapment efficiency, zeta potential, and zeta size were 93.3%, -5.88 mV, and 0.173 µm, respectively. Moreover, melanin, sebum, and skin erythema were significantly reduced while skin elasticity and hydration were improved. Conclusion: It is evident that niacinamide and ferulic acid can be successfully incorporated in a stable multiple emulsion which has potent cosmeceutical effects on human skin.

Overview of nanoparticulate strategies for solubility enhancement of poorly soluble drugs.

Poor aqueous solubility and poor bioavailability are major issues with many pharmaceutical industries. By some estimation, 70-90% drug candidates in development stage while up-to 40% of the marketed products are poorly soluble which leads to low bioavailability, reduced therapeutic effects and dosage escalation. That's why solubility is an important factor to consider during design and manufacturing of the pharmaceutical products. To-date, various strategies have been explored to tackle the issue of poor solubility. This review article focuses the updated overview of commonly used macro and nano drug delivery systems and techniques such as micronization, solid dispersion (SD), supercritical fluid (SCF), hydrotropy, co-solvency, micellar solubilization, cryogenic technique, inclusion complex formation-based techniques, nanosuspension, solid lipid nanoparticles, and nanogels/nanomatrices explored for solubility enhancement of poorly soluble drugs. Among various techniques, nanomatrices were found a promising and impeccable strategy for solubility enhancement of poorly soluble drugs. This article also describes the mechanism of action of each technique used in solubilization enhancement.

Synthesis and Evaluation of Finasteride-Loaded HPMC-Based Nanogels for Transdermal Delivery: A Versatile Nanoscopic Platform.

Herein, we report nanogels comprising diverse feed ratio of polymer hydroxypropyl methylcellulose (HPMC), monomer acrylic acid (AA), and cross-linker methylene bisacrylamide (MBA) fabricated for transdermal delivery of finasteride (FIN). Free radical solution polymerization method with subsequent condensation was employed for the synthesis using ammonium per sulfate (APS) and sodium hydrogen sulfite (SHS) as initiators. Carbopol-940 gel (CG) was formulated as assisting platform to deliver FIN nanogels transdermally. Developed formulations were evaluated by several in vitro, ex vivo, and in vivo parameters such as particle size and charge distribution analysis, Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray diffractogram (XRD), rheological testing, in vitro swelling and drug release, and ex vivo skin permeation, irritation, and toxicity assessment. The results endorsed the nanogel formation (117.3 ± 29.113 nm), and the impact of synthesizing method was signified by high yield of nanogels (≈91%). Efficient response for in vitro swelling and FIN release was revealed at pH 5.5 and 7.4. Skin irritation and toxicity assessment ensured the biocompatibility of prepared nanocomposites. On the basis of the results obtained, it can be concluded that the developed nanogels were stable with excellent drug permeation profile across skin.

Investigation of Euphorbia nivulia-HAM for Enzyme Inhibition Potential in Relation to the Phenolic and Flavonoid Contents and Radical Scavenging Activity.

Euphorbia nivulia-Ham (EN) is a neglected medicinal plant traditionally used for a number of pathologies, but it has not been explored scientifically. In the current study, its various fractions were assessed for their phenolic and flavonoid content, radical scavenging, as well as its enzyme inhibitory potential. The hydro-alcoholic crude extract (ENCr) was subjected to a fractionation scheme to obtain different fractions, namely n-hexane (ENHF), chloroform (ENCF), n-butanol (ENBF), and aqueous fraction (ENAF). The obtained results revealed that the highest phenolic and flavonoid content, maximum radical scavenging potential (91 ± 0.55%), urease inhibition (54.36 ± 1.47%), and α-glucosidase inhibition (97.84 ± 1.87%) were exhibited by ENCr, while the ENBF fraction exhibited the highest acetylcholinestrase inhibition (57.32 ± 0.43%). Contrary to these, hydro-alcoholic crude as well as the other fractions showed no significant butyrylcholinestrases (BChE) and carbonic anhydrase inhibition activity. Conclusively, it was found that EN possesses a significant radical scavenging and enzyme inhibitory potential. Thus, the study may be regarded a step forward towards evidence-based phyto-medicine.

Phenolic, flavonoid content and radical scavenging activity of Smilax china with its inhibitory potential against clinically important enzymes.

Smilax china (SC) is a medicinal plant that has been traditionally used for a number of pathological disorders. In current study, its various fractions were assessed for radical scavenging, phenolic, flavonoid content and enzyme inhibition. The methanolic extract (MSC) of SC was subjected to fractionation using different solvents including n-hexane, benzene, chloroform, ethyl acetate and n-butanol. Results revealed that ethyl acetate fraction showed maximum phenolic (101.81 ± 0.13 mg GAE/g) and flavonoid (96.80 ± 0.39 mg QE/g) content with maximum radical scavenging potential (82.51 ± 0.18%, IC50=104.45 µg/ml) as well as urease (82.63 ± 0.79%), tyrosinase (81.30 ± 0.41%) and Butyrylcholinesterase (BChE) (62.47 ± 0.76%) inhibition at 0.5 mg/ml. Whereas, maximum α-Glucosidase (87.56 ± 0.13%) and Acetylcholinesterase (AChE) inhibition (82.34 ± 0.64%) was exhibited by n-hexane and benzene fractions, respectively. Present study has revealed the promising radical scavenging, phenolic, flavonoid and enzyme inhibitory potential of various fractions of SC extract. Thus, the study is a step forward towards evidence-based phyto-medicine.

HPLC profiling of Mimosa pudica polyphenols and their non-invasive biophysical investigations for anti-dermatoheliotic and skin reinstating potential.

Plant-derived polyphenols are known to have promising biological activities including antioxidant and antityrosinase and may be a potential candidate for anti-dermatoheliotic remedy. The present study was performed to investigate the polyphenolic contents of Mimosa pudica (MP) seed extract and its anti-dermatoheliotic potential using non-invasive biophysical techniques after developing a stable topical emulgel formulation. Moreover, its in-vitro cytotoxicity was also evaluated using normal Human keratinocytes (HaCat cells) to rule out any cellular incompatibility. The results revealed that MP seed extract, constituted with a number of polyphenolic compounds, has very good antioxidant and anti-tyrosinase potential. There were significant positive effects (p ≤ 0.05) invoked by its topical emulgel formulation on various dermatoheliotic associated skin parameters like erythema, melanin, elasticity, hydration, and sebum as compared to placebo. In the meantime, it was also found to be biocompatible and did not show any effect on HaCat cell viability and structure. In conclusion, the topical emulgel preparation loaded with MP seed extract could be a great strategy to deal with dematoheliosis.

Transdermal patches: Design and current approaches to painless drug delivery.

Use of transdermal patches can evade many issues associated with oral drug delivery, such as first-pass hepatic metabolism, enzymatic digestion attack, drug hydrolysis and degradation in acidic media, drug fluctuations, and gastrointestinal irritation. This article reviews various transdermal patches available in the market, types, structural components, polymer role, and the required assessment tools. Although transdermal patches have medical applications for smoking cessation, pain relief, osteoporosis, contraception, motion sickness, angina pectoris, and cardiac disorders, advances in formulation development are ongoing to make transdermal patches capable of delivering more challenging drugs. Transdermal patches can be tailored and developed according to the physicochemical properties of active and inactive components, and applicability for long-term use. Therefore, a number of chemical approaches and physical techniques for transdermal patch development are under investigation.

Plant derived anticancer agents: A green approach towards skin cancers.

Plants have been used as medicinal agents since the origin of mankind. High cost and severe side effects associated with conventional chemotherapy has limited their general acceptability and fuel up the search for alternate options. The alternative treatment options like phytochemicals have come up with ease of availability and cost effectiveness. Owing to their general acceptance, safety, low side effects and multistep targeting in signal transduction pathways, plant derived phyto-constituents have promising anti-carcinogenic potential for skin related cancers. This leads to the surge in research of new phytochemicals for the prevention and cure of a variety of skin cancers which are major cause of morbidity and mortality in present world. Although very limited clinical data involving humans is available in literature to demonstrate favorable eff ;ects of phyto-constituents on various types of skin carcinomas yet the topical treatment with these plant derived anticancer phytochemicals is very promising. There are various mechanisms and pathways responsible for antitumor activity of plant derived medicinal compounds such as loss of mitochondrial membrane potential, release of cytochrome-c, Down regulation of Anti-apoptotic proteins and Up regulation of pro-apoptotic proteins, Activation of Caspase, Fas, FADD, p53 and c-Jun signaling pathway, Inhibition of Akt signaling pathway, phosphorylation of ERK, P13K, Raf, survivin gene, STAT 3 and NF-kB. In-vitro testing of skin cancer cell lines models offers the opportunity for identifying mechanisms of action of compounds from plant origin against variety of skin related cancers. This review thus aims at providing an overview of plant derived anti-cancer compounds which have been reported to show promising anti-carcinogenic effects against various skin cancer cell lines and on animal models. Phytochemicals that are discussed in this review include steroids, coumarines, trepenes, essential oils, alkaloids, esters, ethers, resins, phenols and flavonoids. This review also provides information about marketed formulations developed so far from plant derived compounds for skin cancer prevention and treatment.

Phytocosmeceutical formulation development, characterization and its in-vivo investigations.

Several plants found rich in flavonoid, polyphenols, and antioxidants reported antiaging, oppose inflammation and carcinogenic properties but have rarely been applied in dermatology. The present study was an active attempt to formulate a stable phytocosmetic emulsion system loaded with 2% pre-concentrated Prosopis cineraria bark extract, aiming to revive facial skin properties. In order to obtain potent therapeutic activities, we first prepared extracts of stem, leaves, and bark and screen them on basis of phenolic, flavonoids contents and antioxidant, antibacterial, lipoxygenase and tyrosinase inhibition activities. Furthermore, cytocompatibility of the extract was also determined prior starting in vivo investigations. Then the in vivo performance of 2% bark extract loaded emulsion formulation was determined by using non-invasive probe cutometer and elastometer with comparison to base formulation. The preliminary experiment showed that bark extract has a significant amount of phenolic and flavonoid compounds with eminent antioxidant potential. Furthermore, indicated an efficient antibacterial, lipoxygenase, and tyrosinase enzyme inhibition activities. Importantly, the bark extract did not induce any toxicity or apoptosis, when incubated with HaCat cells. Moreover, the in vivo results showed the formulation (size 3 µm) decreased the skin melanin, erythema and sebum contents up to 2.1-,2.7-and 79%, while increased the skin hydration and elasticity up to 2-folds and 22% as compared to the base, respectively. Owing to enhanced therapeutic effects the phytocosmetic formulation proved to be a potential skin whitening, moisturizer, anti-acne, anti-wrinkle, anti-aging therapy and could actively induce skin rejuvenation and resurfacing.

Aglycone solanidine and solasodine derivatives: A natural approach towards cancer.

Over the past few years, it was suggested that a rational approach to treat cancer in clinical settings requires a multipronged approach that augments improvement in systemic efficiency along with modification in cellular phenotype leads to more efficient cell death response. Recently, the combinatory delivery of traditional chemotherapeutic drugs with natural compounds proved to be astonishing to deal with a variety of cancers, especially that are resistant to chemotherapeutic drugs. The natural compounds not only synergize the effects of chemotherapeutics but also minimize drug associated systemic toxicity. In this review, our primary focus was on antitumor effects of natural compounds. Previously, the drugs from natural sources are highly precise and safer than drugs of synthetic origins. Many natural compounds exhibit anti-cancer potentials by inducing apoptosis in different tumor models, in-vitro and in-vivo. Furthermore, natural compounds are also found equally useful in chemotherapeutic drug resistant tumors. Moreover, these Phyto-compounds also possess numerous other pharmacological properties such as antifungal, antimicrobial, antiprotozoal, and hepatoprotection. Aglycone solasodine and solanidine derivatives are the utmost important steroidal glycoalkaloids that are present in various Solanum species, are discussed here. These natural compounds are highly cytotoxic against different tumor cell lines. As the molecular weight is concerned; these are smaller molecular weight chemotherapeutic agents that induce cell death response by initiating apoptosis through both extrinsic and intrinsic pathways.