Ashish Baldi

Comparative Insight of Regulatory Guidelines for Probiotics in USA, India and Malaysia: A Critical Review

Probiotics have always been a unique category of natural products due to established evidences of their applications in wellness of human beings. Inspite of being based on live microorganisms, commercial exploration of probiotics as biologics, pharmaceuticals, food and nutritional supplements has witnessed a tremendous increase due to their potential of providing health benefits. Currently different regulatory bodies across the globe consider probiotics under several categories depending upon their intended use. In order to clear the ambiguity related to regulatory specifications, assurance of quality and premarketing safety assessment for drafting of comprehensive guidelines with global acceptance is need of the hour. The aim of this paper is to compare existing regulations in countries like United States, India and Malaysia to develop harmonized guidelines for approval of probiotics.

Development and characterization of arteether-loaded nanostructured lipid carriers for the treatment of malaria

The purpose of the present work is to improve the antimalarial activity of the drug arteether (AE) by enhancing its solubility, by loading it into a nanostructured lipid carrier (NLC). The in vitro drug release profile of the NLC showed 93% drug release in 32 h. Complete eradication of the parasite from the blood and efficient anti-malarial pharmacological activity were observed, with the use of AE-loaded NLCs. These results suggest that nanolipid carriers of AE could be a promising carrier system to deliver the poorly soluble antimalarial drug through the oral route, by enhancing its solubility as well as preventing its degradation in the stomach.

Exploring Therapeutic Potential of Nanocarrier Systems Against Breast Cancer

BACKGROUNDnBreast cancer is the most widely occurring non-cutaneous cancer in women. Treatment options available for breast cancer are limited and there are a number of toxicity concerns associated with them. Therefore, nanocarrier based approaches have been explored for breast cancer treatment. Nanocarriers implemented for breast cancer treatment are nanoliposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, gold nanoparticles, dendrimers, and protein nanocages.nnnOBJECTIVEnObjective of this review was to explore the therapeutic efficacy of various nanocarrier systems against breast cancer.nnnMETHODnExisting literature regarding nanocarrier systems for breast cancer therapy was reviewed using Pubmed and Google Scholar.nnnRESULTSnNanocarriers may show prolonged circulation time of chemotherapeutic agent with efficient breast tumor targeting. Both active and passive targeting methodologies can be explored to target breast cancer cells using different nanocarriers. Targeted nanocarriers have the capability to reduce side effects caused by various conventional formulations used to treat breast cancer.nnnCONCLUSIONnVarious nanocarriers listed above have shown their therapeutic potential in preclinical studies to treat breast cancer. Satisfactory clinical evaluation and scale up techniques can promote their entry into the pharmaceutical market in greater extent.

Self-assembled nanomicelles of amphiphilic clotrimazole glycyl-glycine analogue augmented drug delivery, apoptosis and restrained melanoma tumour progression

In present investigation, self-assembled nanomicelles of amphiphilic clotrimazole glycyl-glycine (CLT-GG-SANMs) analogue were customized for augmenting drug delivery, permeability and apoptosis in B16F1 mouse melanoma cancer cells both in vitro and in vivo following intratumoral (i.t.) route of administration. The mean particle size of CLT-GG-SANMs was measured to be 35.9u202f±u202f3.4u202fnm in addition to zeta-potential of -17.1u202f±u202f3.5u202fmV. The shape of CLT-GG-SANMs was visualized to be smooth and spherical as like nanoparticles. The critical micellar concentration (CMC) of CLT-GG-SANMs was estimated to be 17u202fμg/ml using DPH (1,6-diphenyl-1,3,5-hexatriene) as a UV probe. Modification of CLT to CLT-GG-SANMs induced the amorphization in therapeutic moiety. Next, CLT suspension released only 9.7% of the drug within 1u202fh under dissolution testing and further analysis up to 48u202fh did not display any remarkable effect on the drug release. On the other hand, CLT-GG-SANMs released 46.2% of the drug significantly (Pu202f<u202f0.01) higher than CLT suspension at 4u202fh. The IC50 of CLT-GG-SANMs was measured to be 15.1-μM significantly (Pu202f<u202f0.05) lower than CLT suspension (IC50u202f>u202f20u202fμM) in B16F1 cells. Western blotting and histopathological analysis also supported the superior therapeutic efficacy of CLT-GG-SANMs in terms of higher extent of apoptosis, tumour regression and exhibition of strong antioxidant potential against B16F1 cells induced tumour in C57BL6J mice. In conclusion, in vitro and in vivo therapeutic efficacy analysis indicated that CLT-GG-SANMs may be a potential candidate for translating in to a clinically viable product.

Chloroquine diphosphate bearing dextran nanoparticles augmented drug delivery and overwhelmed drug resistance in Plasmodium falciparum parasites

Chloroquine diphosphate (CHQ) is primarily used for the treatment of Plasmodium falciparum malaria at the dose of 500mg orally or 10mg/kg parenterally. However, point mutations in Plasmodiumfalciparum chloroquine resistance transporter (PfCRT) protein and Plasmodium falciparum multidrug resistance protein 1 (Pfmdr1) localized in digestive vacuole membrane, are responsible for CHQ resistance. Therefore, in present investigation, dextran nanoparticles bearing chloroquine diphosphate (CHQ-DEX-NPs) were formulated by solvent diffusion method of size below 70nm with zeta-potential of -20.1±3.2mV. FT-IR, DSC and PXRD techniques confirmed the successful loading of drug in nanomatrix system with amorphous attributes. In vitro drug release analysis indicated the Higuchi pattern with diffusion controlled drug release. The IC50 of CHQ-DEX-NPs in sensitive (3D7) and resistant (RKL9) Plasmodium falciparum strains was estimated to be 0.031-μg/ml and 0.13-μg/ml significantly lower than 0.059-μg/ml and 0.36-μg/ml of CHQ. The augmented therapeutic efficacy of CHQ-DEX-NPs may be credited to deposition of tailored nanoparticles in food vacuoles of malaria parasites owing to the affinity of parasite towards DEX that consequently lower the drug resistance and improved the therapeutic index. In conclusion, CHQ-DEX-NPs must be evaluated under a set of stringent in vivo parameters to establish its therapeutic efficacy in preclinical model.

Ultrasound, microwave and Box-Behnken Design amalgamation offered superior yield of gum from Abelmoschus esculentus: Electrical, chemical and functional peculiarity

Abstract Background and objective In present investigation, ultrasonic assisted followed by microwave irradiation involving extraction process was developed under the umbrella of Box-Behnken design for gaining superior yield of gum from okra fruit, Abelmoschus esculentus . Methods and results Stationed on single factor layout, Box-Behnken design was employed to calculate the optimized conditions for isolating the okra fruit gum (OFG) using ultrasonic waves and microwave radiations. The extracted gum was further characterized for particle size, zeta-potential, surface morphology, thermal stability, functional groups, and polymorphism. The optimized conditions like water to raw material ratio of 44.98u202fml/g, extraction time of 40u202fmin and ultrasonic power of 60u202fW provided the uppermost extraction yield of 31.52%u202f±u202f0.22% that was analogous to the predicted value. The average mean diameter of OFG was measured to be 256.3u202f±u202f18.4u202fnm in addition to the zeta potential of −9.85u202f±u202f0.12u202fmV. SEM image of OFG powder revealed irregular, rough surfaced and amorphous structure of OFG powder. The degree of esterification was measured to be 7.8 with high thermal stability, as exposed by DSC. The FT-IR spectrum of OFG displayed a broad peak at 3405.20u202fcm −1 announcing presence of OH group and hydrophilicity attribute. The spectrum also presented the small peak at 1605.20u202fcm −1 ( C O) owing to the presence of galacturonic acid besides galactose and rhamnose. Conclusion In conclusion, ultrasound and microwave irradiation assisted extraction process under the shed of Box-Behnken design offered superior yield of OFG that may be used as a pharmaceutical excipient for designing medicated or health products.

Armamentarium of nanoscaled lipid drug delivery systems customized for oral administration: In silico docking patronage, absorption phenomenon, preclinical status, clinical status and future prospects

Poor drug solubility and bioavailability remain a significant and frequently encountered concern for pharmaceutical scientists. Nanoscaled lipid drug delivery systems (NSLDDS) have exhibited great potentials in oral delivery of poorly water-soluble drugs, primarily for lipophilic drugs, with several successful clinical products. In the past few years, we have find out that optimized composition of drug in lipid, surfactant, or mixture of lipid and surfactant omits the solubility, permeability and bioavailability issues, which are potential limitations for oral absorption of poorly water-soluble drugs. Lipids not only vary in structures and physiochemical properties, but also in their digestibility and absorption pathway; therefore selection of lipid excipients and dosage form has a pronounced effect on biopharmaceutical aspects of drug absorption and distribution both in vitro and in vivo. Therefore, in current critical review, a comprehensive overview of the different lipid based nanostructured drug delivery systems intended for oral administration has been presented. In addition, implication of in silico docking in designing of NSLDDS as well as mechanism of absorption of different lipid based nanoformulations through intestinal absorption window has also been offered. Moreover, attention has also been paid to NSLDDS that are currently undergoing preclinical or clinical analysis.

Intratumoral administration of carboplatin bearing poly (ε-caprolactone) nanoparticles amalgamated with in situ gel tendered augmented drug delivery, cytotoxicity, and apoptosis in melanoma tumor

BACKGROUND AND OBJECTIVEnIn a phase II clinical trial, carboplatin (CBDCA) displayed the response rate of 19% equivalent to dacarbazine in the treatment of malignant melanoma. However, besides desirable therapeutic profile, intravenous (i.v) administration of CBDCA delivers a subtherapeutic concentration at the target site. This entails administration of CBDCA through an alternate route by using nanovectors to achieve therapeutic efficacy in the treatment of melanoma.nnnMETHODS AND RESULTSnCarboplatin loaded poly(ε-caprolactone) nanoparticles (CBDCA-PCL-NPs) were formulated and amalgamated with chitosan-β-glycerophosphate gel (CBDCA-PCL-NPs-Gel) for intratumoral (i.t) administration. The mean particle size and zeta-potential of CBDCA-PCL-NPs were determined to be 54.5u202f±u202f6.3-nm and -8.1u202f±u202f0.9-mV, in addition to spherical shape of the nanoformulation. FT-IR spectroscopy denied any issue of chemical incompatibility between drug and polymer. XRD pattern indicated the amorphous lattice of CBDCA-PCL-NPs. The drug loading capacity of CBDCA-PCL-NPs-Gel was estimated to be 152u202fmg/1u202fml. CBDCA-PCL-NPs-Gel demonstrated prolonged drug release up to 48u202fh. Furthermore, CBDCA-PCL-NPs-Gel displayed the IC50 of 80.3-μM significantly (Pu202f<u202f0.05) lower than 162.8-μM of CBDCA-PCL-NPs and 248.5-μM of CBDCA solution in B16F1, melanoma cancer cells. CBDCA-PCL-NPs-Gel verified 80.2% of apoptosis significantly (Pu202f<u202f0.01) higher than 57.6% of CBDCA-PCL-NPs and 43.4% of CBDCA solution. Continuation to this, CBDCA-PCL-NPs-Gel significantly (Pu202f<u202f0.01) suppressed the tumor volume to 95.5u202f±u202f8.4-mm3 as compared to 178.9u202f±u202f10.2-mm3 of CBDCA solution injected i.t. and 210.6u202f±u202f17.1-mm3 displayed by CBDCA solution injected i.v. vis-à-vis 815.4u202f±u202f17.1-mm3 tumor volume of B16F1 tumor bearing C57BL6J mice.nnnCONCLUSIONnThe promising preclinical results of CBDCA-PCL-NPs-Gel warrant further investigations under a set of stringent parameters for the treatment of melanoma.

Drug metabolizing enzymes and their inhibitors' role in cancer resistance

Despite continuous research on chemotherapeutic agents, different mechanisms of resistance have become a major pitfall in cancer chemotherapy. Although, exhaustive efforts are being made by several researchers to target resistance against chemotherapeutic agents, there is another class of resistance mechanism which is almost carrying on unattended. This class of resistance includes pharmacokinetics resistance such as efflux by ABC transporters and drug metabolizing enzymes. ABC transporters are the membrane bound proteins which are responsible for the movement of substrates through the cell membrane. Drug metabolizing enzymes are an integral part of phase-II metabolism that helps in the detoxification of exogenous, endogenous and xenobiotics substrates. These include uridine diphospho-glucuronosyltransferases (UGTs), glutathione-S-transferases (GSTs), dihydropyrimidine dehydrogenases (DPDs) and thiopurine methyltransferases (TPMTs). These enzymes may affect the role of drugs in both positive as well negative manner, depending upon the type of tissue and cells present and when present in tumors, can result in drug resistance. However, the underlying mechanism of resistance by drug metabolizing enzymes is still not clear. Here, we have tried to cover various aspects of these enzymes in relation to anticancer drugs.

Good Agricultural Practices: A Prequisite Approach forEnhancing the Quality of Indian Herbal Medicines

Global and national markets for medicinal plants are growing at a reckless pace and are earning significant profits. India has proved itself of being the epicenter of the trading of botanicals [1]. According to the reports of National Plants Medicinal Board (NMPB) India, India has 1,95,000 domestic herbal industries, 1,34,500 export value ( dry Weight in MT), 1,67,500 MT (on dry weight basis) rural household demand, 14910 wastage, making 5,11,910 (Dry wt. in MT) a total annual demand of herbal raw drugs for the year 201415. The trade value of herbal raw drugs, estimated to be consumed in the country during the year 2014-15, works out to around US