Mahavir Chougule

Mercer University · Department of Pharmaceutical Sciences

The oral administration of sildenafil citrate (SC) for the treatment of pulmonary arterial hypertension is associated with several drawbacks. The study aimed to design and formulate SC-loaded inhalable poly (lactic-co-glycolic acid) [PLGA] large porous microparticles (LPMs) for pulmonary delivery. A factorial design was used to study the effect of...

Gelatin nanoparticles (GNPs) have been extensively engineered by desolvation processes. However, engineering monodisperse GNPs of reproducible size remains a challenge. Therefore, the starting material processing steps such as gelatin solution pH adjustment and incubation time prior to desolvation were investigated to understand their implications...

Polymers are repeated structural units of one or more monomeric units. Several polymers have been investigated preclinically in vitro and in vivo in animals to evaluate their use in pulmonary drug delivery. The major concern associated with the use of polymeric systems for pulmonary drug delivery is their safety, biocompatibility, stability, and cl...

This study summarizes the synthesis, characterization, and evaluation of a library of biocompatible self-assembling Janus dendrimers (JDs) and their resulting nanostructures possessing either a cationic (NH3+), anionic (COO-), or neutral (OH) surface. Strategically designed for applications in therapeutic delivery, the dendrimers are comprised of a...

This study represents a successful approach towards employing polycaprolactone - polyamidoamine (PCL-PAMAM) LDBC nano-aggregates as small molecule carriers in NIR imaging and photothermal therapy. A feasible and robust synthetic strategy was used to synthesize a library of amphiphilic LDBCs with well-controlled hydrophobic to hydrophilic weight rat...

The capabilities of principal component regression (PCR) and multiple linear regression (MLR) were evaluated to decipher and predict the impact of formulation and process parameters on the modeled metronidazole benzoate (MB)–ethyl cellulose (EC) microsponge (MBECM) properties. MBECM were prepared by a quasi-emulsion solvent diffusion method. A mini...

Under the heading "Methods-Synthesis of the Bioreducible Modified-PAE (mPAE)", on page 3, line 14-17, there is an error. The quantity unit of PAE and 2-iminothiolane hydrochloride needs to be corrected to mg instead of g.

Low-order high-energy nifedipine (NIF) solid dispersions (SDs) were generated by melt solvent amorphization with PEG 1450 and HPMCAS-HF to increase NIF solubility while achieving acceptable physical stability. HPMCAS-HF was used as a crystallization inhibitor. Individual formulation components, their physical mixtures (PMs), and SDs were characteri...

Purpose Lung cancer is one of the leading causes of deaths in the United States, but currently available therapies for lung cancer are associated with reduced efficacy and adverse side effects. Small interfering RNA (siRNA) can knock down the expression of specific genes and result in therapeutic efficacy in lung cancer. Recently, mTOR siRNA has be...

Lung cancer constitutes a group of aggressive malignant tumors and causes the most cancer deaths than any other form of cancer. Lung cancer treatment is extremely complicated due to various adverse effects associated with conventional chemotherapy as it targets both normal and tumor cells with equal intensity. Development of cancer cell resistance,...

Most of the biologically active compounds are struggle with low solubility and therefore low bioavailability, biological degradation and inadvertent intrinsic side effects. To overcome such difficulties, the emergence of potential and novel drug carrier system is of supreme importance in terms of their efficient applicability through different rout...

A technology of 21st century, nanotechnology has the potential to transform almost every area of applications right from making a needle to robot. It is basically involves manipulating physical, chemical, biological and optical properties at the nanoscale, often involving dimensions that ranging from 1-100 nm. In the field of medicine, it has alrea...

Lipid nanoparticles offer multifaceted drug delivery to cancer. To date, various lipid nanoparticles, ranging from phospholipid-based liposomes to second generation solid lipid nanoparticles, i.e., nanostructured lipid nanoparticles are explored for drug delivery of anticancer drugs. An ample amount of research has been done on emulsions (in nano o...

In Hawai'i, lung cancer is among the top cancers diagnosed and a leading cause of death. Despite current understanding and modern surgery, radiology , and chemotherapy techniques, the survival of those suffering from lung cancer remains low. Current anticancer drugs have poor tumor tissue selectivity and toxicity issues that contribute to their ove...

The density, porosity, breaking force, viscoelastic properties, and the presence or absence of any structural defects or irregularities are important physical-mechanical quality attributes of popular solid dosage forms like tablets. The irregularities associated with these attributes may influence the drug product functionality. Thus, an accurate a...

Background: Aerosol delivery of chemotherapeutic nanocarriers represents a promising alternative for lung cancer therapy. This study optimized gemcitabine (Gem)-loaded gelatin nanocarriers (GNCs) cross-linked with genipin (Gem-GNCs) to evaluate their potential for nebulized lung cancer treatment. Methods: Gem-GNCs were prepared by two-step desol...

In this article, applications of engineered nanoparticles containing siRNA for inhalation delivery are reviewed and discussed. Diseases with identified protein malfunctions may be mitigated through the use of well-designed siRNA therapeutics. The inhalation route of administration provides local delivery of siRNA therapeutics to the lungs for vario...

Lung cancer is the leading cause of cancer deaths in both men and women in the United States accounting for about 27% of all cancer deceases. In our effort to develop newer therapy for lung cancer, we evaluated the combinatory antitumor effect of siRNA targeting VEGF and the PI3K/mTOR dual inhibitor PF-04691502. We analyzed the anticancer effect of...

The proportion of the global population aged 60 years and over is steadily increasing and projected to increase to almost 30 % in 2050. Among the various health problems, eye and vision problems are serious issues in the elderly. These may be manifested as basic functional disabilities or a decline in the receptive, storage, and analytical capaciti...

Desired characteristics of nanocarriers are crucial to explore its therapeutic potential. This investigation aimed to develop tunable bioresponsive newly synthesized unique arginine grafted poly (cystaminebisacrylamide-diaminohexane) [ABP] polymeric matrix based nanocarriers of using L9 Taguchi factorial design, desirability function, and multivari...

This article reviews the pulmonary route of administration, aerosol delivery devices, characterization of pulmonary drug delivery systems, and discusses the rationale for inhaled delivery of siRNA. Diseases with known protein malfunctions may be mitigated through the use of siRNA therapeutics. The inhalation route of administration provides local d...

Purpose: To formulate hydroxypropyl methylcellulose-stabilized self-emulsifying solid dispersible carriers of noscapine to enhance oral bioavailability. Methods: Formulation of noscapine (Nos) self-emulsifying solid dispersible microparticles (SESDs) was afforded by emulsification using an optimized formula of Labrafil M1944, Tween-80, and Labra...

Nanotechnology and combination therapy are two major fields that show great promise in the treatment of cancer. The delivery of drugs via nanoparticles helps to improve drug's therapeutic effectiveness while reducing adverse side effects associated with high dosage by improving their pharmacokinetics. Taking advantage of molecular markers over-expr...

The topical application of therapeutic agent has shown promising efficacy in the treatment of skin disorders. The siRNA based therapies have been used for treatment of various disorders including skin diseases. The topical delivery of siRNA based therapies has opened new perspectives for the treatment of skin disorders. The use of siRNA is limited...

Onconase (ONC) is a member of a ribonuclease superfamily that has potent cytostatic activity against malignant mesothelioma (MM). However, the recent clinical trials have failed due to unfavorable biopharmaceutical characteristics. The objective of this investigation was to develop BSA-chitosan based hybrid nanoformulations for the efficient delive...

The nanotechnology-based therapies have demonstrated great promise in revolutionizing cancer medicine by improving efficacy while reducing the adverse effects. Despite recent progress in newer nanotechnologies, the bench-to-bedside translation of nanotechnology-based therapies is very poor. This theme issue of AAPS PharmSciTech provides a broad ove...

Chemotherapeutic agents have certain limitations when it comes to treating cancer, the most important being severe side effects along with multidrug resistance developed against them. Tumor cells exhibits drug resistance due to activation of various cellular level processes viz. activation of drug efflux pumps, anti-apoptotic defense mechanisms etc...

Onconase (ONC) is a member of a ribonuclease superfamily that has cytostatic activity against malignant mesothelioma (MM). The objective of this investigation was to develop bovine serum albumin (BSA)-chitosan based hybrid nanoformulations for the efficient delivery of ONC to MM while minimizing the exposure to normal tissues. Taguchi Orthogonal Ar...

Purpose: Evaluation of tumor targeting pegylated EphA2 peptide coated nanoparticles (ENDDs) of a novel anticancer agent DIM-C-pPhC6H5 (DIM-P) and Docetaxel (DOC) and investigate its antitumor activity and potential for treatment of lung cancer. Methods: Nanoparticles were prepared with DIM-P and DOC (NDDs) using Nano-DeBEE. ENDDs were prepared b...

Abstract The purpose of this study was to investigate the permeation of Noscapine (Nos) across the Caco-2 and Madin-Darby canine kidney (MDCK) cell monolayers and to evaluate the influence of absorption enhancers on in vitro and in vivo absorption of Nos. The bidirectional transport of Nos was studied in Caco-2 and MDCK cell monolayers at pH 5.0-7....

Unlabelled: The drugs/strategies to selectively inhibit tumor blood supply have generated interest in recent years for enhancement of cancer therapeutics. The objective of this study was to formulate tumor homing PEGylated CREKA peptide conjugated theranostic nanoparticles of DIM-C-pPhC6H5 (DIM-P) and investigate in vivo antitumor activity as well...

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Introduction: The intratumoral distribution of tumor targeted nanoparticles (NP) is hindered by dense collagen network and highly fibrous interstitium. Use of antifibrotic agents can decrease tumor interstitial fibrosis and promote NP intratumoral distribution. The objecti...

The aim of this investigation was to develop and evaluate freeze-dried mannosylated liposomes for the targeted delivery of selenium. Dipalmitoylphosphatidylcholine, distearoylphosphatidylglycerol, and cholesterol were dissolved in a chloroform and methanol mixture and allowed to form a thin film within a rotatory evaporator. This thin film was hydr...

Signal transducer and activator of transcription 6 (STAT-6) is a transcription factors that is highly expressed in various types of cancers including lung cancer and its expression was reported to be significantly correlated with tumor progression. Several studies showed that down-regulation of STAT-6 using short interfering RNA (siRNA) leads to th...

Purpose: Evaluation of in-vivo anticancer activity of aerosolized Celecoxib encapsulated Nanolipidcarriers (Cxb-NLC) as a single therapeutic agent and combined with intravenously administered Docetaxel (Doc) against non-small cell lung cancer. Methods: Cxb-NLC were prepared by high-pressure homogenization and were characterized for its physicoch...

Taguchi orthogonal array design is a statistical approach that helps to overcome limitations associated with time consuming full factorial experimental design. In this study, the Taguchi orthogonal array design was applied to establish the optimum conditions for bovine serum albumin (BSA) nanocarrier (ANC) preparation. Taguchi method with L9 type o...

The clinical utility of siRNA therapy has been hampered due to poor cell penetration, nonspecific effects, rapid degradation, and short half-life. We herewith proposed the formulation development of STAT6 siRNA (S6S) nanotherapeutic agent by encapsulating them within gelatin nanocarriers (GNC). The prepared nanoformulation was characterized for siz...

RNAi technology has brought a new category of treatments for cancer. NFκB is a transcription factor which can inhibit apoptosis and promote cell proliferation. Activation of NFκB is linked to the progression of various cancers. Inhibition of NFκB and its downstream targets using NFκB-siRNA (NS) for cancer therapy has been investigated. However, for...

3,3'-Diindolylmethane (DIM) is the major in vivo product of the acid-catalyzed oligomerization of indole-3-carbinol present in cruciferous vegetables. 1, 1-bis (3'-indolyl)-1-(p-substituted phenyl) methanes [C-substituted diindolylmethanes (C-DIMs)] are a new class of anticancer compounds derived from indole 3-carbinol. Despite rapidly increasing k...

The aim of this investigation was to evaluate the anticancer activity of Noscapine (Nos) and Gemcitabine (Gem) combination (NGC) against non-small cell lung cancer (NSCLC) and to elucidate the underlying mechanism of action. Isobolographic method was used to calculate combination index values from cytotoxicity data. In vitro antiangiogenic and apop...

The aim of this study was to investigate the anticancer activity and mechanism of action of Noscapine alone and in combination with Doxorubicin against triple negative breast cancer (TNBC). TNBC cells were pretreated with Noscapine or Doxorubicin or combination and combination index values were calculated using isobolographic method. Apoptosis was...

The purpose of this study was to examine the efficacy of Noscapine (Nos) and Cisplatin (Cis) combination treatment in vitro in A549 and H460 lung cancer cells, in vivo in murine xenograft model and to investigate the underlying mechanism. The combination index values (< 0.6) suggested synergistic effects of Nos+Cis and resulted in the highest incre...

Estrogen receptor negative (ER⁻) breast cancers (∼40%) are clinically aggressive with poor clinical outcome. Combination of different mechanism based antimicrotubular Noscapine and DNA intercalating Doxorubicin may lead to additive/synergistic activity against ER⁻ breast cancer. Clinical utility of safer oral Noscapine (poor bioavailability and sho...

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Objective: In cancer research, three dimensional (3D) cell culture models are rapidly gaining importance as they create a pragmatic microenvironment and mimic an in vivo system, which helps to understand cell-cell interactions. AlgiMatrix sponge (Invitrogen Corporation,...

The purpose of this study was to determine the anticancer efficacy of 1,1-bis (3'-indolyl)-1-(p-biphenyl) methane (DIM-C-pPhC₆H₅) by inhalation delivery alone and in combination with i.v. docetaxel in a murine model for lung cancer. An aqueous DIM-C-pPhC₆H₅ formulation was characterized for its aerodynamic properties. Tumor-bearing athymic nude mic...

The aim of the current study was to encapsulate celecoxib (Cxb) in the nanostructured lipid carrier (Cxb-NLC) nanoparticles and evaluate the lung disposition of nanoparticles following nebulization in Balb/c mice. Cxb-NLC nanoparticles were prepared with Cxb, Compritol, Miglyol and sodium taurocholate using high-pressure homogenization. Cxb-NLC nan...

Liposomal dry powder formulations (DPFs) have proven their superiority over conventional DPFs due to favorably improved pharmacokinetics and pharmacodynamics of entrapped drugs, and thus, reduced local and systemic toxicities. Nanoliposomal DPFs (NLDPFs) provide stable, high aerosolization efficiency to deep lung, prolonged drug release, slow syste...

This study was conducted to examine the cytotoxic effects of a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, 1,1-bis (3'-indolyl)-1-(p-biphenyl) methane (DIM-C-pPhC(6)H(5)), alone and in combination with docetaxel in vitro in A549 lung cancer cells and in vivo in nude mice bearing A549 orthotopic lung tumors. Isobolographic...

Liposomal drug dry powder formulations have shown many promising features for pulmonary drug administration, such as selective localization of drug within the lung, controlled drug release, reduced local and systemic toxicities, propellant-free nature, patient compliance, high dose carrying capacity, stability and patent protection. Critical review...

The purpose of the present study was to investigate the influence of method of preparation of large respirable particles of amikacin sulphate on traits and topography and in-vitro aerosol performance. Large respirable particles of amikacin sulfate (50%w/w) were produced by spray-drying and freeze-drying processes using hydrogenated soyaphosphatidyl...

Liposomal dry powder formulations (DPFs) have proven their superiority over conventional DPFs due to favorably improved pharmacokinetics and pharmacodynamics of entrapped drugs, and thus, reduced local and systemic toxicities. Nanoliposomal DPFs (NLDPFs) provide stable, high aerosolization efficiency to deep lung, prolonged drug release, slow syste...

An antitussive plant alkaloid, Noscapine HCl (Nos) displays anticancer activity and has a safe pharmacological profile in humans. The current study was aimed to investigate the in vitro and in vivo anti tumor activity of Nos to determine possible mechanisms of anti tumor activity for treatment of non-small cell lung cancer (NSCLC). In vitro cytotox...

This investigation was undertaken to evaluate practical feasibility of site specific pulmonary delivery of liposomal encapsulated Dapsone (DS) dry powder inhaler for prolonged drug retention in lungs as an effective alternative in prevention of Pneumocystis carinii pneumonia (PCP) associated with immunocompromised patients. DS encapsulated liposome...

The studies were undertaken to evaluate feasibility of pulmonary delivery of liposomaly encapsulated tacrolimus dry powder inhaler for prolonged drug retention in lungs as rescue therapy to prevent refractory rejection of lungs after transplantation. Tacrolimus encapsulated liposomes were prepared by thin film evaporation technique and liposomal di...

Development of dry powder inhalers involves powder recrystallization, formulation, dispersion, delivery, and deposition of the therapeutic agent in different regions of the airways in prophylaxis/ treatment/ diagnosis of pulmonary and systemic disorders. Conventional powder production by crystallization and milling has many limitations resulting in...

The purpose of this study was to encapsulate Amiloride Hydrochloride into nano-liposomes, incorporate it into dry powder inhaler, and to provide prolonged effective concentration in airways to enhance mucociliary clearance and prevent secondary infection in cystic fibrosis. Liposomes were prepared by thin film hydration technique and then dispersio...

The aim of the study was to optimize and characterize high therapeutic payload large respirable powders prepared by spray-drying technique for maximum fine particle fraction with minimum quantities of excipients. Influence of formulation components was optimized by a three-factor, five-level central composite design having different proportions of...

The purpose of the study was to develop a stable, controlled release Amphotericin B (Amph B) lyophilized mixed micelle (MM) formulation using hydrogenated soya phosphatidylcholine (HSPC) and bile salts in monomeric form and evaluate it for therapeutic performance and side effects. The MM formulations of Amph B were prepared using sodium deoxycholat...

In the present study clobetasol propionate (Cp) was loaded as solid lipid nanoparticles (SLN), incorporated it in suitable cream base and evaluated in vitro and its performance clinically against equivalent marketed formulation. Cp was incorporated into SLN by high-pressure homogenization technique and characterized for mean particle size, surface...