FORMULATION OF PPAR-g AGONIST AS SURFACE MODIFIED PLGA NANOPARTICLES FOR NON-INVASIVE TREATMENT OF DIABETIC RETINOPATHY: IN VITRO AND IN VIVO EVIDENCES
Umesh Laddha*, Sanjay Kshirsagar
MET’s Institute of Pharmacy, Bhujbal Knowledge City, Nashik-422003, MS-India
Diabetic retinopathy (DR) is one of the worst complications of diabetes and currently it is treated by invasive method. We prepared a surface modified poly (D, L-lactide-co-glycolide) i.e. PLGA nanoparticles for delivery of pioglitazone which is a peroxisome proliferator-activated receptor-gamma agonist to posterior segment of the eye by topical administration. The present study investigated two grades of PLGA viz. 75:25 and 50:50. Surface modification was performed using polysorbate 80. Nanoparticles were prepared by single emulsion solvent evaporation method and optimized by using 3-factor 3-level Box-Behnken statistical design. Mean particle size, PDI and entrapment efficiency for optimized batch of PLGA 75:25 was found to be 163.23 nm, 0.286 and 91%, whereas; for PLGA 50:50 it was 171.7 nm, 0.280 and 93% respectively. DSC confirms the molecular dispersion of drug in polymer. In vitro release study showed biphasic drug release pattern with 58.48 ± 1.38% and 74.17 ± 1.38% cumulative drug release by PLGA 75:25 and 50:50 nanoparticles at the end of 10h. The release profile of pioglitazone from nanoparticles appeared to fit best with Higuchi model. Further effectiveness of formulation in treatment of DR was evaluated in diabetes induced rat. After 4 weeks of study the VEGF level in vitreous was found to be less in entire treatment rats as compared to untreated rat. Based on evidence, prepared nanoparticles can be considered as feasible non-invasive treatment of DR.
GLYCOSYLATED MESOPOROUS SILICA NANOPARTICLES FOR THE TREATMENT OF COLORECTAL CANCER
Reema Narayan1*, Usha Y. Nayak1, Sanjay Garg2
1Manipal College of Pharmaceutical Sciences, MAHE, Manipal, Karnataka 576104, INDIA
2UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AUSTRALIA
Mesoporous silica nanoparticles (MSNs) are versatile carriers with high payload capacity, ease of functionalization and biocompatible. The present study deals with the design of pH-sensitive glycosylated mesoporous silica nanoparticles loaded with capecitabine (CAP), an anticancer drug for targeted colorectal cancer therapy. The MSNs showed a loading capacity of 180.51±5.23 mg/g which may be attributed to the larger pores. The MSNs were capped with chitosan-glucuronic acid conjugate to ensure pH-sensitive and lectin receptor uptake of the nanoparticles. The in vitro studies showed a controlled, sustained release of CAP in colonic pH. The developed glycosylated MSNs showed a higher uptake in HCT 116 cell lines and improved efficacy with alleviation in the toxic features when administered to Wistar rats. This illustrated that the nanoparticles showed promising antitumor efficacy with reduced toxicity and may be used as an effective carrier against cancer.
LOCALIZED DELIVERY OF RESVERATROL LOADED NANOSTRUCTURED LIPID CARRIERS VIA MICRONEEDLE ARRAY FOR EFFICIENT THERAPY OF BREAST CANCER
Shivaprasad Gadag*, Usha Y. Nayak
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
Resveratrol (RVT), a phytoconstituent present in grapes and berries has shown promising potential for breast cancer treatment. In spite of proven anticancer potential, the use of RVT is limited due to its low oral bioavailability (<1%) and short plasma half-life. To overcome draw backs, we have developed nanostructured lipid carrier (NLCs) and delivered via microneedle locally to the breast tissue. Design of Experiments approach was used for the optimization of the NLCs. The NLCs were characterized for entrapment efficiency, particle size, polydispersity index, zeta potential, FT-IR, DSC, XRD and TEM analysis. NLCs delivered using microneedle have shown higher permeation of RVT across skin with low skin retention when compared with pure drug. RVT-NLCs have showed high cytotoxicity in MDA-MB-231 breast cancer cell line when compared with pure RVT. Preclinical studies in rats showed RVT-NLCs delivered via microneedles demonstrated a remarkable increase in the Cmax, Tmax and AUC0-inf , and a higher localization in breast tissue compared to pure RVT administered orally. These results suggest that the RVT-NLCs administered by microneedle array system is an effective strategy for the local delivery of RVT for breast cancer therapy.
THIOL FUNCTIONALIZED POLYMER-BASED NASAL NANOCOMPOSITE OF
CENTELLA ASIATICA WITH BRAIN TARGETING POTENTIAL
Hajira Banu Haroon*
1Department of Pharmacology, M. S. Ramaiah University of Applied Sciences, Gnanagangothri Campus, New B.E.L.
Road, M.S.R. Nagar, M.S.R.I.T Post, Bengaluru, Karnataka, India
Among the several limitations associated with the drug delivery to Central Nervous System (CNS), the presence of Blood-Brain-Barrier (BBB) is the major drawback in treating neurodegenerative diseases. Polymeric nanomaterials are being used to overcome this limitation and achieve therapeutic concentrations in the brain. The present study was designed to develop a thiolated polymer-based nanocomposite of Centella asiatica to achieve better brain penetration on administration through the nasal route. Thiolated chitosan was first complexed with Centella and then converted to its nano form by the ionic-gelation method. The nanocomposite was characterized and subjected to ex vivo nasal permeation, nasal cilio toxicity studies, and MTT assay using Human Umbilical Cord Vein Endothelial Cells (HUVECs) mimicking BBB. Further, the targeting efficacy was confirmed by molecular docking studies against receptors associated with BBB. FTIR, XRD, NMR, and MS studies confirmed chemical conjugation of thiolated chitosan with Centella. Nanocomposite characterization was performed by SEM, AFM, and DLS which confirmed the size and stability of the developed nanocomposite. The nanocomposite showed no signs of nasal ciliotoxicity and had good permeation across the nasal mucosa. MTT assay showed that the nanocomposite had lesser toxicity against HUVECs compared to the free drug. The polymer exhibited affinity to the BBB receptors and confirms the ability of polymer based nanocomposite to concentrate in the brain post nasal administration.
FORMULATION AND DEVELOPMENT OF MUCOADHESIVE BUCCAL
TABLETS OF AZITHROMYCIN DIHYDRATE FOR UPPER RESPIRATORY
Roopam G Raut, Raju S Chiluka*
More than 1.5 million deaths annually from respiratory tract infections. Out of which 24% are upper respiratory tract infections. It is crucial to cut down the mortality rate.
Mucoadhesive buccal tablets of azithromycin dihydrate were formulated, varying the amount of natural, synthetic polymers and the glidant. Azithromycin dihydrate is a semisynthetic macrolide antibiotic widely used for the treatment of upper respiratory tract infections.
Mucoadhesive buccal tablets are prepared by mixing the drug and excipients and
subjecting it to direct compression. The powders were evaluated for bulk density, tap density, % compressibility & angle of repose. The tablets were evaluated for hardness, friability, diameter, thickness, drug content, swelling index, surface pH, mucoadhesive strength, in vitro dissolution study & in-vitro residence time.
In DSC & FTIR studies, no evidence of interaction of drug with excipients was found.
A 2 X 3 factorial design was used to study the effect of natural, synthetic polymers and the glidant on mucoadhesive strength and percentage cumulative drug release at 8 hours. The responsive variables were analyzed using ANOVA by Design-Expert version 12.0. It was concluded that these excipients significantly affected the response variables.
The optimized formulation was found to have an adequate mucoadhesion of 4.8 gm and a cumulative percentage release of 80 %. Optimized formulation was found to be stable at room temperature and accelerated temperature for three months