Protamine sulphate coated poly (lactide-co-glycolide) nanoparticles of MUC-1 peptide improved cellular uptake and cytokine release in mouse antigen presenting cells.

AIM: MUC-1-peptide (M-1-pep) loaded poly (lactide-co-glycolide) nanoparticles were coated with protamine sulphate (PS), M-1-pep-PS-P-NPs for targeting antigen presenting cells (APCs) to evoke cytokine release. METHODS AND RESULTS: M-1-pep-PS-P-NPs were tailored by emulsion-diffusion evaporation method and characterised in vitro under a set of rigorous parameters. The average particle size and zeta potential of optimised M-1-pep-PS-P-B-NPs was measured to be 132.21 ± 30.71 nm and 6.29 ± 0.71 mV, significantly (p < 0.01) higher than 71.24 ± 17.76-nm and -43.41 ± 3.37 mV of M-1-pep-P-NPs. Further, 50-µg/ml concentration of M-1-pep-PS-P-B-NPs displayed 82.4% cellular uptake in RAW 264.7 cells calculated in setting of fluorescence intensity significantly (p < 0.05) elevated than 63.1% of M-1-pep-P-NPs. Consistent to quantitative results, M-1-pep-PS-P-B-NPs also confirmed advanced cellular uptake (CU) in RAW 264.7 cells in contrast to M-1-pep-P-NPs suppose to be through multiple mechanisms including phagocytosis and clathrin mediated endocytosis. CONCLUSION: M-1-pep-PS-P-B-NPs must be evaluated in vivo through inhalation route of administration for antitumor prospective in lung cancer xenograft model.

Non-small cell lung cancer tumour antigen, MUC-1 peptide-loaded non-aggregated poly (lactide-co-glycolide) nanoparticles augmented cellular uptake in mouse professional antigen-presenting cells: optimisation and characterisation.

Aim: MUC-1 lipopeptide vaccine exhibited immense potential in the treatment of non-small cell lung cancer (NSCLC) in both preclinical and clinical trials. However, it lacks triggering of mucosal immunity at the site of action. Therefore, in present investigation, MUC-1 peptide-loaded poly(lactide-co-glycolide) nanoparticles (MUC-1 peptide-PLGA-NPs) and MUC-1 peptide-loaded poly(lactide-co-glycolide) non-aggregated nanoparticles (MUC-1 peptide-PLGA-NA-NPs) using Central Composite Design (CCD) were customised.Methods and Results: The mean particle size of MUC-1 peptide PLGA-NPs was estimated to be 176.7 ± 32.7 nm, significantly (p < 0.05) higher than 100.3 ± 24.3 nm of MUC-1 peptide-PLGA-NA-NPs. Furthermore, integrity and stability of MUC-1 were maintained in MUC-1 peptide PLGA-NA-NPs. MUC-1 peptide-PLGA-NA-NPs exhibited augmented cellular uptake in mouse RAW264.7 macrophages preferably by clathrin-mediated endocytosis pathway as compared to phagocytosis followed by MUC-1-peptide PLGA-NPs owing to size ≤100 nm, and spherical shape.Conclusion: MUC-1 peptide-PLGA-NA-NPs may be a potential candidate to study antitumor potential in xenograft model of NSCLC through inhalation route of administration.

Systematically Optimized Imiquimod-Loaded Novel Hybrid Vesicles by Employing Design of Experiment (DoE) Approach with Improved Biocompatibility, Stability, and Dermatokinetic Profile.

The present research work explored the possibility of harnessing the benefits of vesicular carriers for overcoming imiquimod-associated complaints or side effects. Hybrid vesicles were prepared by the most common and easily scalable method, i.e., thin film hydration. The chaffing of myriad of factors, both process and material related, affecting the desirable attributes of conceived vesicles, was performed through Taguchi design. Based upon the analysis of Pareto chart and prior experiences, concentration of phospholipid and poloxamer 407 was selected for optimization by 2 levels, 13 run central composite design (CCD). The optimized hybrid vesicles contained 1% w/v phospholipid and 3% w/v poloxamer 407. The optimized hybrid vesicles were incorporated into the 3% w/v carbopol 940 gel and characterized for morphology, physicochemical properties, and rheological behavior. The release (%) and skin retention (% of total dose) across rat skin from gel at same amount of formulation was more than Imiquad®. The gel delivered the loaded cargo, preferably, in the viable region of skin and formed local depot in confocal microscopic studies. The gel followed one compartment open body dermatokinetic model in rat skin. There was not any harmful effect on the mice skin after repeated applications. The gel was stable at room conditions for 1 year.

Effective Topical Delivery of H-AgNPs for Eradication of Klebsiella pneumoniae-Induced Burn Wound Infection.

The aim of the present study was to explore the therapeutic efficacy of microemulsion-based delivery of histidine-capped silver nanoparticles in eradicating Klebsiella pneumoniae-induced burn wound infection. The developed microemulsion was characterized on the basis of differential light scattering, phase separation, refractive index, and specific conductance. Emulgel was prepared and characterized on the basis of thixotropy, texture, differential scanning calorimetry, and release kinetics. Emulgel was further evaluated in skin irritation and in vivo studies, namely full-thickness K. pneumoniae-induced burn wound infection treatment via topical route. Efficacy of treatment was evaluated in terms of bacterial load, histopathology, wound contraction, and other infection markers. The developed emulgel provided significant in vivo antibacterial activity of histidine-capped silver nanoparticle preparations via topical route and resulted in reduction in bacterial load, wound contraction, and enhanced skin healing as well as decrement of inflammatory markers such as malondialdehyde, myeloperoxidase, and reactive nitrogen intermediate compared to untreated animals. The present study encourages the further employment of histidine-capped silver nanoparticles along with microemulsion-based drug delivery system in combating antibiotic-resistant topical infections.

Beta-carotene-Encapsulated Solid Lipid Nanoparticles (BC-SLNs) as Promising Vehicle for Cancer: an Investigative Assessment.

Beta-carotene (BC), a red-colored pigment found in plants and animals, is one of the most extensively investigated carotenoids due to its provitamin-A, antioxidant, and anticancer properties. The anticancer activity of BC through oral administration is severely affected due to its low bioavailability and oxidative degradation. The present study aimed to formulate and characterize solid lipid nanoparticles (SLNs) of BC for enhanced bioavailability and therapeutic efficacy. Beta-carotene-loaded solid lipid nanoparticles (BC-SLNs) were prepared employing different combinations of glyceryl monostearate and gelucire. The characterization studies were performed for particle size, morphology, release behavior, and stability. BC-SLNs were also studied for in vitro cytotoxicity in human breast cancer cell lines (MCF-7) and pharmacokinetic studies in Wistar rats. The cytotoxicity studies confirmed that encapsulation of BC within the lipid bilayers of nanoparticles did not affect its anticancer efficacy. An improved anticancer activity was observed in BC-SLNs as compared to the free BC. BC-SLNs enhanced the bioavailability of BC on oral administration by sustaining its release from the lipid core and prolongation of circulation time in the body. Similarly, area under the curve (AUCtotal) enhanced 1.92-times more when BC was incorporated into SLNs as compared to free BC. In conclusion, solid lipid nanoparticles could be an effective and promising strategy to improve the biopharmaceutical properties of carotenoids for anticancer effects.

Oral Delivery of Methylthioadenosine to the Brain Employing Solid Lipid Nanoparticles: Pharmacokinetic, Behavioral, and Histopathological Evidences.

The present study aimed to orally deliver methylthioadenosine (MTA) to the brain employing solid lipid nanoparticles (SLNs) for the management of neurological conditions like multiple sclerosis. The stearic acid-based SLNs were below 100 nm with almost neutral zeta potential and offered higher drug entrapment and drug loading. Cuprizone-induced demyelination model in mice was employed to mimic the multiple sclerosis-like conditions. It was observed that the MTA-loaded SLNs were able to maintain the normal metabolism, locomotor activity, motor coordination, balancing, and grip strength of the rodents in substantially superior ways vis-à-vis plain MTA. Histopathological studies of the corpus callosum and its subsequent staining with myelin staining dye luxol fast blue proved the potential of MTA-loaded SLNs in the remyelination of neurons. The pharmacokinetic studies provided the evidences for improved bioavailability and enhanced bioresidence supporting the pharmacodynamic findings. The studies proved that SLN-encapsulated MTA can be substantially delivered to the brain and can effectively remyelinate the neurons. It can reverse the multiple sclerosis-like symptoms in a safer and effective manner, that too by oral route.

Preclinical Explorative Assessment of Celecoxib-Based Biocompatible Lipidic Nanocarriers for the Management of CFA-Induced Rheumatoid Arthritis in Wistar Rats.

Celecoxib (CXB), a COX-2 inhibitor, is primarily indicated for long-term treatment of rheumatoid arthritis (RA). The effective therapeutic efficacy of CXB on RA via oral administration shows adverse systemic complications, and therefore, local application of CXB has been recommended. The aim of the present study was to develop and characterize solid lipid nanoparticles (SLNs) with enhanced skin permeation potential of CXB. The particle size, polydispersity index (PDI), and percentage drug entrapment (PDE) of the developed SLNs (CXB-SLNs) were found to be 240 nm, < 0.3, and ~ 86% respectively. The developed SLNs exhibited sustained release up to 70% at the end of 48 h. Drug permeation was found to be 45% for SLN gel and 31% for conventional gel. The dermatokinetic studies also confirmed enhanced permeation of CXB in the epidermis and dermis and revealed superiority of the developed SLN gel vis-à-vis the conventional gel. Further, in the CFA-induced arthritis rat model, % arthritis index (AI) of the CXB-SLN gel formulation was found to be very less (18.54%) as compared to untreated (187.34%) and conventional gel-treated (91.61%) animals. In conclusion, the current study can provide a suitable alternative for the development of an effective topical formulation of CXB in lipid nanocarriers.

Chitosan-Stearic Acid Based Polymeric Micelles for the Effective Delivery of Tamoxifen: Cytotoxic and Pharmacokinetic Evaluation.

Chitosan is a widely employed polysaccharide with positive zeta-potential and better tissue/cell adhesion. Its hydrophilicity, high viscosity, and insolubility at physiological pH are major hurdles in proper utilization of this macromolecule. Therefore, it was conjugated with biocompatible stearic acid and the conjugate was employed to develop polymeric micelles for delivery of tamoxifen to breast cancer cells. The conjugate was characterized by FT-IR and NMR, and the nanocarrier was characterized for micromeritics, surface charge, drug loading, and morphological attributes. The efficacy was evaluated by in vitro MTT studies, safety by erythrocyte compatibility, and biodistribution by in vivo pharmacokinetic studies. Despite better drug loading and sustained drug release, cytotoxicity on MCF-7 breast cancer cells was substantially enhanced and the pharmacokinetic profile was significantly modified. The AUC was enhanced manifolds along with reduced clearance. The findings are unique and provide an alternative to the conventional lipid-based nanocarriers for better dose delivery, tissue adhesion, and desired pharmacokinetic modulation.

In vivo efficacy of single phage versus phage cocktail in resolving burn wound infection in BALB/c mice.

Klebsiella pneumoniae is one of the most predominant pathogens associated with burn wound infections, causing considerable morbidity and mortality. The indiscriminate usage of antibiotics has led to the development of resistant strains, which have contributed towards the inefficacy of antibiotics. Phage therapy is a promising alternative to hinder the progression of pathogenic bacteria. However, phage bacterial resistance is already well known but the use of phage cocktails can overcome this drawback. The aim of the study was to evaluate the therapeutic efficacy of monophage (Kpn1, Kpn2, Kpn3, Kpn4 and Kpn5) in comparison to phage cocktail in resolving the course of burn wound infection in mice. Although, animals receiving monophage therapy exhibited efficacy in resolving the course of infection but phage cocktail was highly effective in arresting the entire infection process (bacterial load, wound contraction, skin myeloperoxidase activity, collagen formation and histopathological analysis). In comparison to untreated control mice, a significant reduction in bacterial load to 4.32, 4.64, 4.42, 4.11 and 4.27 log CFU/ml in Kpn1, Kpn2, Kpn3 Kpn4 and Kpn5 treated animals was obtained respectively was on peak day (3rd day). However, the group receiving phage cocktail (group 7) showed maximum reduction in bacterial load in the skin tissue. The bacterial load was significantly reduced to 3.01 log CFU/ml on peak day. This accounts for a significant reduction of 6 log cycles (p < 0.01) as compared to that of untreated control animals where a peak of 8.81 log CFU/ml was seen followed by steady decrease thereafter. Thus, phage cocktail gave maximum protection against burn wound infection by K. pneumoniae B5055. Compared to any single phage, phage cocktail significantly checked the emergence of resistant mutants. Hence this approach can serve as an effective strategy in treating Klebsiella mediated burn wound infections in individuals who do not respond to conventional antibiotic therapy.

The ligand (s) anchored lipobrid nanoconstruct mediated delivery of methotrexate: an effective approach in breast cancer therapeutics.

The present study was designed to engineer surface-anchored and methotrexate loaded lipobrid nano-constructs for targeting breast cancer. Ligands (fucose, galactose and mannose) anchored lipobrid nano-constructs were used to compare and assess delivery efficiency in breast cancer cell lines as well as in DMBA induced breast cancer animal model. The developed and characterized formulations were used to comparatively assess cellular uptake, cell-viability, apoptosis, lysosomal membrane permeability, bioavailability, bio-distribution, changes in tumor volume and animal survival. Our results show greater cellular uptake, cytotoxicity at low IC50, apoptosis with altered lysosomal membrane permeability and greater rate of degradation of lysosomal membrane. We saw better bioavailability and tumor targeting efficiency with minimum secondary organ drug distribution. The significant reduction was seen in tumor burden with ligand anchored lipobrids in comparison to plain and MTX-lipobrid formulations. In conclusion, fucose anchored MTX-lipobrid formulation showed promising results, and warrants to explore the development of therapeutic interventions for breast cancer.

Sigma-2 receptor ligand anchored telmisartan loaded nanostructured lipid particles augmented drug delivery, cytotoxicity, apoptosis and cellular uptake in prostate cancer cells.

Recently, the anticancer activity of telmisartan (TEL) has been discovered against prostate cancer. Nevertheless, despite favorable therapeutic profile, poor aqueous solubility and suboptimal oral bioavailability hamper the anticancer efficacy of TEL. Therefore, in this investigation, sigma-2 receptor ligand, 3-(4-cyclohexylpiperazine-1-yl) propyl amine (CPPA) anchored nanostructured lipid particles of telmisartan (CPPA-TEL-NLPs) were engineered using stearic acid for targeting prostate cancer, PC-3 cells. The mean particle size of TEL-NLPs was measured to be 25.4 ± 3.2 nm, significantly (p < 0.05) lower than 32.6 ± 5.3 nm of CPPA-TEL-NLPs. Correspondingly, the zeta-potential of TEL-NLPs was measured to be -15.4 ± 2.3 mV significantly (p < 0.05) higher than -9.6 ± 2.7 mV of CPPA-TEL-NLPs. The encapsulation efficiency of CPPA-TEL-NLPs was estimated to be 72.7 ± 4.3%, significantly (p < 0.05) lower than 77.5 ± 5.4%, displayed by TEL-NLPs. In addition, FT-IR and PXRD confirmed the molecular encapsulation of the drug in amorphous state. In vitro drug release study was conducted to determine the drug delivery potential of tailored nanoparticles. TEL-NLPs released 93.36% of drug significantly (p < 0.05) higher than 85.81%, released by CPPA-TEL-NLPs in 24 h. The IC50 of CPPA-TEL-NLPs was measured to be 20.3 µM significantly (p < 0.05) lower than 36.3 µM presented by TEL-NLPs in PC-3 cells. In contrast, CPPA-TEL-NLPs displayed the IC50 of 41.3 µM, significantly (p > 0.05) not different from 43.4 µM, exhibited by TEL-NLPs in PNT-2 cells. We elucidated that CPPA-TEL-NLPs entered the PC-3 cells via receptor mediated endocytosis pathway and thus exhibited superior cytotoxicity, apoptosis and greater extent of cellular uptake in PC-3 cells. In conclusion, CPPA-TEL-NLPs may be a promising nanomedicine and warrant further in vivo investigations for gaining clinical success.

Formulation, characterisation and in vivo evaluation of lipid-based nanocarrier for topical delivery of diflunisal.

Diflunisal (DIF) is non-steroidal anti-inflammatory drug used in the treatment of rheumatoid arthritis, osteoarthritis. The current engrossment was aimed at formulation and assessment of DIF-loaded solid lipid nanoparticles (SLNs) for topical/dermal application. SLNs formulated by hot homogenisation method based on microemulsification technique were spherical with a mean size of 124.0 ± 2.07 nm; PDI 0.294 ± 0.15. The cumulative amount permeated/area was 109.99 ± 0.008 µg/cm(2), along with permeation flux (6.30 ± 0.09 µg/cm(2)/h) and skin retention (11.74 ± 0.155 µg/cm(2)) across mice skin. The SLNs of DIF showed significant decrease in fluid volume, granuloma tissue weight, leukocyte count/mm(3) after application of SLN formulation in mice air pouch model. Similarly, in mice ear oedema and rat paw oedema model, there was 2.30 and 1.29 time increase in percentage inhibition of oedema after SLN formulation application, respectively, as compared with conventional cream. Hence, the SLNs of DIF may prove to be a potential nanocarrier to effectively treat the local inflammatory conditions associated with arthritis.

Bacteriophage-loaded nanostructured lipid carrier: improved pharmacokinetics mediates effective resolution of Klebsiella pneumoniae-induced lobar pneumonia.

This study examined the therapeutic and prophylactic potential of bacteriophages in a mouse model of Klebsiella pneumoniae lobar pneumonia. Phages were administered intraperitoneally. Liposome-entrapped phages (LP) were effective in treating infection, even when therapy was delayed by 3 days after the induction of pneumonia. In contrast, nonliposomal phages provided protection when administered 24 hours after infection. Administration of nonliposomal phages 6 hours prior to intranasal bacterial challenge resulted in complete protection, compared with LP, which was effective even when administered 48 hours prior to infection. Increased reduction and a greater increment in the levels of proinflammatory and antiinflammatory cytokines, respectively, in homogenates of lung from LP-treated mice were suggestive of increased efficacy of LP in the treatment of pneumonia. This is the first study to assess liposomes as a delivery vehicle for phage, and the results confirm the superiority of LP for both therapeutic and prophylactic applications.

Biocompatible lidocaine and prilocaine loaded-nanoemulsion system for enhanced percutaneous absorption: QbD-based optimisation, dermatokinetics and in vivo evaluation.

Barrier properties of the skin and physicochemical properties of the drugs are the main hiccups in delivering local anaesthetic molecules topically. The present work endeavours for systematic optimisation and evaluation of nanoemulsions (NEs) of local anaesthetic drugs, lidocaine and prilocaine, employing the systematic approach of Quality by Design. A 3(3) Box-Behnken design was employed for systematic optimisation of the factors obtained from screening studies employing Plackett-Burman design and risk assessment studies. The superior permeation rates, and higher concentrations of the drugs in skin layers from the optimised NE carriers, were achieved in permeation and dermatokinetic studies, when compared to marketed cream. Furthermore, rapid onset of action was demonstrated by the NE system in rabbit eye corneal reflex model and biocompatibility was confirmed from the absence of any marked skin change(s) in the normal skin histology. The developed NE systems demonstrated it as a promising carrier for topical delivery of lidocaine and prilocaine.

Sustained-release protamine sulphate-impregnated microspheres may reduce the frequent administration of recombinant interferon α-2b in ovarian cancer: in-vitro characterization.

Parenteral administration of recombinant interferon-α-2b (rINF-α-2b) at a dose of 50×10 IU once a week for 8 weeks is recommended for ovarian cancer. However, short half-life, small therapeutic index and proteolytic degradation cause fluctuations in plasma level and pose barriers in the development of a clinically viable dosage form. Therefore, in the present investigation, fluorescein isothiocynate-tagged rINF-α-2b was loaded into stearic acid (*rINF-α-2b-SMs), pectin (*rINF-α-2b-PMs) and gelatin (*rINF-α-2b-GMs) microspheres. Parameters such as particle size, ζ potential, encapsulation efficiency and in-vitro release were studied to follow the optimization process. The formulation, *rINF-α-2b-GMs of particle size 8.3±2.1 µm with an encapsulation efficiency of 76.0±7.4%, offered 97.4% of *rINF-α-2b release at 288 h. Thus, negatively charged extended-release formulation *rINF-α-2b-GMs was then tethered with a gradient concentration (5-20 mg/ml) of a cationic arginine-rich protein stabilizer, protamine sulphate (Pt). The nanoformulation, *rINF-α-2b-Pt-GMs-15 superimposed with 15 mg/ml of Pt, released 95.0% of *rINF-α-2b at 336 h and was designated as the optimized formulation. The optimized formulation also conserved the primary and secondary structure of *rINF-α-2b as analysed by gel electrophoresis and circular dichroism. Moreover, in-vitro cytotoxicity analysis of SKOV3 cells of the optimized nanoformulation reported significantly (one-way analysis of variance test, P<0.05) lower IC50 (414.3 IU/ml) compared with *rINF-α-2b-GMs (514.3 IU/ml) and pure rINF-α-2b (628.6 IU/ml) at 72 h by offering a prolonged cytotoxic effect. Therefore, *rINF-α-2b-Pt-GMs-15, a promising nanomedicine, warrants further in-depth in-vivo study to scale up the technology for clinical translation.

Lipid-based capsaicin-loaded nano-colloidal biocompatible topical carriers with enhanced analgesic potential and decreased dermal irritation.

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 microemulsification and rotary-evaporation for various attributes. The results demonstrated that microemulsion 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 rheologically accepted formulation for the treatment of pain-associated disorders.

Novel phospholipid-based topical formulations of tamoxifen: evaluation for antipsoriatic activity using mouse-tail model.

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.

Nanocolloidal carriers of isotretinoin: antimicrobial activity against Propionibacterium acnes and dermatokinetic modeling.

Acne, a common skin disease in teenagers, is caused by Propionibacterium acnes (P. acnes). Isotretinoin (ITR) is though reported to have immense antiacne potential, yet there are hardly any reports vouching its antimicrobial activity. The present study, therefore, was undertaken to study the antimicrobial activity of ITR and evaluate the effect of its encasement in nanocarriers on its minimum inhibitory concentration (MIC). The nanocarriers were also evaluated for the skin transport characteristics. MICs of pure drug and entrapped drug in nanolipid carriers (ITR-NLCs) and in solid lipid nanoparticles (ITR-SLNs) were determined by broth dilution method against clindamycin phosphate as the reference antibiotic. It was observed that ITR possessed marked antimicrobial activity against anaerobic pathogen, P. acnes. Nanocarriers loaded with ITR, that is, SLNs and NLCs, enhanced the antimicrobial activity even at lower concentrations vis-à-vis the drug alone and improved drug transport potential vis-à-vis the commercial gel. The unique findings could be the result of effective adhesion of ITR-loaded nanocarriers to the bacterial membranes and release of drug directly to the target. Besides establishing ITR as an antimicrobial agent against acne-causing bacteria, the current work ratifies immense potential of nanocolloidal carriers like SLNs and NLCs to treat acne in a more efficient manner.

Poly (ethylene)-glycol conjugated solid lipid nanoparticles of noscapine improve biological half-life, brain delivery and efficacy in glioblastoma cells.

Noscapine crosses blood-brain-barrier and inhibits proliferation of glioblastoma cells. However, short plasma half-life and rapid elimination necessitate the administration of multiple injections for successive chemotherapy. Noscapine bearing solid lipid nanoparticles, Nos-SLN and poly (ethylene)-glycol conjugated solid lipid nanoparticles of noscapine, Nos-PEG-SLN of 61.3 ± 9.3-nm and 80.5 ± 8.9-nm containing 80.4 ± 3.2% and 83.6 ± 1.2% of Nos, were constructed. First order kinetic and Higuchi equation were followed to release the Nos at intracellular pH~4.5. Further, a decrease in IC50 (Nos; 40.5 µM>Nos-SLN; 27.2 µM>20.8 µM) and enhanced subG1 population were observed in U87cells. Plasma half-life was enhanced up to ~11-fold and ~5-fold by Nos-PEG-SLN and Nos-SLN which significantly (P<0.05) deposits 400.7 µg/g and 313.1 µg/g of Nos in comparison to 233.2 µg/g by drug solution. This is first report demonstrating a workable approach to regulate the administration of multiple injections of Nos, warranting further in vivo tumor regression study for superior management of brain cancer. FROM THE CLINICAL EDITOR: This report describes a possible approach to regulate the administration of multiple injections of Noscapine using solid lipid nanoparticles. The data warrant further in vivo tumor regression studies for optimal management of glioblastoma, a generally very poorly treatable brain cancer.

Improved therapeutic performance of dithranol against psoriasis employing systematically optimized nanoemulsomes.

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.