Exploration of Nanoethosomal Transgel of Naproxen Sodium for the Treatment of Arthritis.

BACKGROUND: The present work aimed to develop an ethosomal gel of naproxen sodium for the amelioration of rheumatoid arthritis. OBJECTIVE: In the present work, we have explored the potential of ethosomes to deliver naproxen into deeper skin strata. Further, the anti-inflammatory efficacy of naproxen ethosomal formulation was assessed using the carrageenan-induced rat paw edema model. METHODS: Naproxen sodium nanoethosomes were prepared using different proportions of lipoid S100 (50mg-200mg), ethanol (20-50%) and water, and were further characterized on the basis of vesicle morphology, entrapment efficiency, zeta potential, in-vitro drug release and ex-vivo permeation studies. RESULTS: The optimized ethosomal formulation was found to have 129 ± 0.01 nm particle size, 0.295 Polydispersity Index (PDI), -3.29 mV zeta potential, 88% entrapment efficiency and 96.573% drug release in 24 hours. TEM and SEM analysis of the optimized formulation showed slightly smooth spherical structures. The Confocal laser scanning microscopy showed that ethosomes could easily infiltrate into deeper dermal layers (upto 104.9µm) whereas the hydroalcoholic solution of the drug could penetrate up to 74.9µm. Further, the optimized ethosomal formulation was incorporated into 1% carbopol 934 gel base and optimized wherein the transdermal flux was found to be approximately 10 times more than the hydroethanolic solution. Also, the in-vivo pharmacodynamic study of the optimized ethosomal gel exhibited a higher percentage inhibition of swelling paw edema than marketed diclofenac gel. CONCLUSION: The ethosomal gel was successfully developed and has shown the potential to be a good option for the replacement of conventional therapies of rheumatoid arthritis.

Design of expert guided investigation of native L-asparaginase encapsulated long-acting cross-linker-free poly (lactic-co-glycolic) acid nanoformulation in an Ehrlich ascites tumor model.

Present study explores native L-asparaginase encapsulated long-acting cross-linker-free PLGA-nanoformulation in an Ehrlich ascites tumor model. L-asparaginase-PLGA nanoparticles for tumor were prepared using a double emulsion solvent evaporation technique, optimized and validated by Box-Behnken Design. L-ASN-PNs showed a particle size of 195 nm ± 0.2 nm and a PDI of 0.2. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) techniques revealed its smooth morphology and elicited an in-vitro release of 80% of the drug, following the Higuchi drug release model. In-vivo studies of L-ASN-PNs on an Ehrlich ascites tumor (EAT) model were completed and compared with the standard medication of 5-fluorouracil (5-FU) treatment. L-ASN-PN treated mice showed a 51.15% decrease in tumor volume and 100% survival rate with no reduction in body weight, no haemotoxicity and no hepatotoxicity, as evident from the hematological parameters, and liver enzyme parameters that were well within the prescribed limits. Chemotherapy has severe side effects and restricted therapeutic success. Henceforth, the purported L-Asparaginase PLGA nanoparticles are a suitable entity for better tumor regression, intra-tumor accumulation and no hematological side-effects.

Formulation and optimization of topotecan nanoparticles: In vitro characterization, cytotoxicity, cellular uptake and pharmacokinetic outcomes.

The study focuses on widening up the therapeutic perspective of anti-cancer therapy by entrapping a hydrophilic anticancer drug, topotecan hydrochloride (TOPO) in biodegradable poly (lactide-co-glycolide) (PLGA) matrix to form topotecan nanoparticles (TOPO NPs) by a double emulsion solvent evaporation technique. Statistical optimization using Box-Behnken design showed that sonication time of primary emulsion for 120 s, drug: polymer ratio of 1:12.65, organic phase: external aqueous phase ratio of 1:2.82 and 0.5% w/v of polyvinyl alcohol in the drug containing phase produced TOPO NPs with a size of 243.2 ±â€¯4 nm and an entrapment efficiency of 60.9 ±â€¯2.2%. TOPO NPs illustrated sustained release of TOPO for a week in phosphate buffer saline (PBS) at simulating physiological (pH 7.4) and acidic tumor microenvironmental (pH 6.5) conditions. A dramatic increase in cellular uptake with a corresponding enhanced cytotoxic potency was also displayed by TOPO NPs against human ovarian cancer cells (SKOV3) over time as compared to native drug, TOPO. These findings were further supported by the enhancement of bioavailability (13.05 fold) conferred by TOPO NPs from the in vivo pharmacokinetic study. The study represents a logistic approach for formulating TOPO NPs which can be used as an effective drug delivery system for the treatment of ovarian cancer.

A vaginal drug delivery model.

Efficient drug delivery at vaginal cavity is often a challenge owing to its peculiar physiological variations including vast differences in pH. Keeping in view this attribute of the target site, the current work was aimed at developing formulation strategies which could overcome this and successfully deliver molecules like itraconazole through SLNs. Optimized SLNs with the given composition was selected for further development into mucoadhesive and thermosensitive gel. Stearic acid and Compritol 888 (1:1, w/w ratio) as lipid, a mixture of 3% Poloxomer 188 and 0.5% sodium taurocholate as surfactant and organic to aqueous ratio of 10:50 was taken. Carbopol 934 and Pluronic F 127 were taken for the development of gel. Optimized gel exhibited a desired gelling temperature (35 °C); viscosity (0.920 PaS) and appreciable in vitro drug release (62.2% in 20 h). MTT assay did not show any cytotoxic effect of the gel. When evaluated in vivo, it did not exhibit any irritation potential despite appreciable bioadhesion. A remarkable decrease in CFUs was also observed in comparison with control and marketed formulation when evaluated in rat infection model. Thus, the proposed study defines the challenges for developing a suitable formulation system overcoming the delivery barriers of the vaginal site.

Revisiting the nanoformulation design approach for effective delivery of topotecan in its stable form: an appraisal of its in vitro Behavior and tumor amelioration potential.

Topotecan (TPT) is indicated against a variety of solid tumors, but has restricted clinical use owing to associated pharmaceutical caveats. This study is focused at formulating a successful TPT PLGA nanosystem which ameliorates the rapid conversion of active lactone form of drug to its inactive carboxylate form and consequently improvises its efficacy. TPT PLGA nanoparticles were formulated by a double emulsion-solvent evaporation technique with sequential optimization to obtain desired particle size, PDI, zeta potential, and entrapment efficiency. Stability of TPT was ensured by maintaining an acidic pH in the drug-containing phase and the system was evaluated for in vitro-in vivo performance including cytotoxic potency. The optimized nanosystem had a particle size of 187.33 ± 7.50 nm, a PDI of 0.179 ± 0.05, and an entrapment efficiency of 56 ± 1.2%. Low pH in the interior of nanoparticles stabilized the drug to remain in its active lactone form and revealed a biphasic release pattern till 15 d. Additionally, an in vitro cytotoxicity testing as well as in vivo antitumor efficacy demonstrated a significant potential of higher proliferation inhibition as compared with neat drug (TPT). Thus, the investigation summarized an innovative simple tool for developing stable TPT NPs for effective delivery for treating solid tumors.

Nanopotentiated combination cancer therapy: Chemotherapeutic and chemosensitizer (2C approach).

An insight into the complex cancer pathophysiology reveals that a dependable amelioration of the disease could only be envisaged with a multipronged treatment approach. It is highly evident that singular chemotherapeutic agents used in clinical practice have shown limitations like severe side effects, MDR and are often associated with poor QOL while combinations of drugs have yielded better therapeutic outcomes. The current hypothesis takes it a step forward wherein a chemotherapeutic agent is combined with a natural chemosensitizer, both loaded into a nanopotentiated particulate system, which would eventually deliver the drug cargo at the target site with certitude. The encapsulated natural bioactive would then favorably act on the tumor milieu through multiple portals and chemosensibilize the cells towards cytotoxic action of the synthetic drug moiety. This 2C (chemotherapeutic and chemosensitizer) approach along with nanosystem's attributes like high payload, prolonged action and diminished side effects would proffer a more dependable treatment modality. In conclusion, the proposed system would be a value addition to the currently available armamentarium of cancer treatment tools.

Topotecan-tamoxifen duple PLGA polymeric nanoparticles: investigation of in vitro, in vivo and cellular uptake potential.

The dual drug loaded poly(dl-lactic-co-glycolic acid) (PLGA(1)) nanoparticles (TOP-TAM NPs(2)) concurrently delivering topotecan hydrochloride (TOP(3)) and tamoxifen citrate (TAM(4)) were developed to achieve synergism for the treatment of breast cancer by enhancing the permeation of TOP through the gut and the cells present in the breast. TAM acted as P-glycoprotein (P-gp(5)) inhibitor, reduced the side effects of individual drugs by reducing the dose. The NPs were prepared by double emulsion (w/o/w) method. The optimized TOP-TAM NPs were found to have smooth and spherical morphology by using SEM(6) and TEM(7) technique. Similarly size of nanoparticles was found to be 151.2 ± 1.6 nm with 0.147 ± 0.03 polydispersity index (PDI(8)). The percentage entrapment efficiency of 95.17 ± 3.57 and 57.77 ± 2.2 was found for TAM and TOP respectively. The lyophillized nanoparticles under DSC(9) showed amorphous nature of both TOP and TAM. In an in vitro release study the release of drugs from TOP-TAM NPs was found to follow the Higuchi pattern. The ex vivo gut permeation study revealed that the TAM enhanced the permeation of TOP and increased its bioavailability by 1.9 folds. The permeation and activity of combination of drugs were further confirmed by carrying out cell line studies on MCF-7 cells.