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Naringenin (NRG) inhibits the fungal 17β-hydroxysteroid dehydrogenase accountable for ergosterol synthesis in Candida albicans (C. albicans), a causative agent for cutaneous candidiasis. In present research, NRG was complexed with ZnO nanomaterial (NRG-Zn 2+ ) to synthesize NRG-Zn 2+ nanocomposites. The particle size and ζ-potential of NRG-Zn 2+ nanocomposites were respectively estimated to be 180.33 ± 1.22-nm and - 3.92 ± 0.35-mV. In silico data predicted the greater affinity of NRG-Zn 2+ nanocomposite for 14α-demethylase and ceramide in comparison to NRG alone. Later, NRG-Zn 2+ nanocomposites solution was transformed in to naringenin-zinc oxide nanocomposites loaded chitosan gel (NRG-Zn-CS-Gel) with viscosity and firmness of 854806.7 ± 52386.43 cP and 698.27 ± 10.35 g, respectively. The ex-vivo skin permeation demonstrated 70.49 ± 5.22% skin retention, significantly greater (P < 0.05) than 44.48 ± 3.06% of naringenin loaded chitosan gel (NRG-CS-Gel) and 31.24 ± 3.28% of naringenin solution (NRG Solution). NRG-Zn-CS-Gel demonstrated 6.71 ± 0.84% permeation of NRG with a flux value of 0.046 ± 0.01-µg/cm 2 /h. The MIC 50 of NRG-Zn-CS-Gel against C. albicans was estimated to be 0.156-µg/mL with FICI (fractional inhibitory concentration index) of 0.018 that consequently exhibited synergistic efficacy. Further, NRG-Zn-CS-Gel demonstrated superior antifungal efficacy in C. albicans induced cutaneous candidiasis infection in Balb/c mice. The fungal burden in NRG-Zn-CS-Gel treated group was 109 ± 25 CFU/mL, significantly lower (P < 0.05) than positive control (2260 ± 446 CFU/mL), naringenin loaded chitosan gel (NRG-CS-Gel; 928 ± 127 CFU/mL) and chitosan gel (CS-Gel; 2116 ± 186 CFU/mL) treated mice. Further, histopathology examination and cytokine profiling of TNF-α, IL-1β and IL-10 revealed the healing of skin and inflammation associated with cutaneous candidiasis infection. In conclusion, NRG-Zn-CS-Gel may be a potential candidate for translating in to a clinical viable topical nanotherapeutic., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Burn is the immense public health issue globally. Low and middle income countries face extensive deaths owing to burn injuries. Availability of conventional therapies for burns has always been painful for patients as well as expensive for our health system. Pharmaceutical experts are still searching reliable, cheap, safe and effective treatment options for burn injuries. Fusidic acid is an antibiotic of choice for the management of burns. However, fusidic acid is encountering several pharmaceutical and clinical challenges like poor skin permeability and growing drug resistance against burn wound microbes like Methicillin resistant Staphylococcus aureus (MRSA). Therefore, an effort has been made to present a concise review about molecular pathway followed by fusidic acid in the treatment of burn wound infection in addition to associated pros and cons. Furthermore, we have also summarized chitosan and phospholipid based topical dermal delivery systems customized by our team for the delivery of fusidic acid in burn wound infections on case-to-case basis. However, every coin has two sides. We recommend the integration of in-silico docking techniques with natural biomacromolecules while designing stable, patient friendly and cost effective topical drug delivery systems of fusidic acid for the management of burn wound infection as future opportunities., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In present investigation, doxorubicin (Dox) and soluble curcumin (Cur-2-HP-β-CD-complex) combination was simultaneously loaded in inhalable bioresponsive chitosan microspheres (Dox/Cur-2-HP-β-CD-complex-elastin-CMs) bearing a substrate-stimuli, elastin. The mean particle size and mean aerodynamic diameter of inhalable bioresponsive microspheres displayed noteworthy differences after incorporation of elastin. Moreover, combination of Dox and soluble curcumin was molecularly dispersed in microspheres matrix as substantiated by a range of spectral techniques. Inhalable bioresponsive microspheres released astonishingly higher amount of Dox in presence of elastase enzyme at pH∼5.5 in comparison to pH∼7.4. However, the release of soluble curcumin from tailored bioresponsive microspheres in presence of elastase enzyme was independent of pH. Consistently, inhalable bioresponsive microspheres exhibited outstandingly lower IC 50 of 3.4-μM in comparison to 6.5-μM of inhalable drug loaded microspheres (Dox/Cur-2-HP-β-CD-complex-CMs) bearing no elastin, against A549, non-small cell lung cancer cells. The superior therapeutic profile of inhalable bioresponsive microspheres may be attributed to enhanced drug release and consequently augmented drug exposure to A549 cells expressing elastase enzyme. In this way, stimuli triggered drug release from tailored inhalable bioresponsive microspheres boosted the phenomena of apoptosis in A549 cells. In conclusion, Dox/Cur-2-HP-β-CD-complex-elastin-CMs warrant further in-vivo tumor regression study to prove its therapeutic efficacy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Soluble telmisartan and telmisartan were loaded in to poly (ethylene-glycol) grafted chitosan nanoparticles (S-TEL-PEG-CNPs and TEL-PEG-CNPs) for targeting cervical cancer through non-invasive, intravaginal route. The mean particle size of S-TEL-PEG-CNPs was measured to be 23.4±5.9-nm significantly (P<0.05) higher than 16.2±3.2-nm of TEL-PEG-CNPs. In contrast, the zeta-potential (-21.5±4.6-mV) of S-TEL-PEG-CNPs was insignificantly (P>0.05) different from -23.8±3.7-mV of TEL-PEG-CNPs. In addition, S-TEL-PEG-CNPs exhibited higher percent mucoadhesiveness (40.2%) in comparison (P<0.05) to 31.4% of TEL-PEG-CNPs, although it was lower than CNPs (100%). S-TEL-PEG-CNPs displayed significantly (P<0.01) higher dissolution of drug, 92.5% in comparison to 31.6% from TEL-PEG-CNPs up to 24h. Furthermore, S-TEL-PEG-CNPs exhibited superior cytotoxicity, apoptosis and cellular uptake, analyzed in human cervical cancer, HeLa cells. The IC 50 of S-TEL-PEG-CNPs was measured to be 22.3-μM significantly (P<0.05) lower than 40.1-μM of TEL-PEG-CNPs. S-TEL-PEG-CNPs induced higher extent of apoptosis (P<0.05) in HeLa cells as compared to TEL-PEG-CNPs, owing to higher diffusion of drug across biological membrane. Finally, quantitative and qualitative cellular uptake assay confirmed the greater endocytosis of S-TEL-PEG-CNPs in HeLa cells due to diffusion, amorphization, hydrophilicity, and submicron size particularly, below 100nm. In conclusion, S-TEL-PEG-CNPs warrant further in vivo tumour regression study to scale up the technology for clinical translation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In present investigation, initially curcumin was complexed with 2-HP-β-CD (curcumin-2-HP-β-CD-complex) in 1:1 ratio and later amalgamated with chitosan microspheres (curcumin-2-HP-β-CD-CMs) for selective delivery in colon only through oral route of administration. Various analytical, spectral and in-silico docking techniques revealed that the curcumin was deeply inserted in the 2-HP-β-CD cavity with apparent stability constant of 3.35×10 -3 M. Furthermore, the mean particle size of 6.8±2.6μm and +39.2±4.1mV surface charge of curcumin-2-HP-β-CD-complex-CMs in addition to encapsulation efficiency of about 79.8±6.3% exhibited that the tailored microspheres were optimum for colon delivery of curcumin. This was also demonstrated in dissolution testing and standard cell proliferation assay in which curcumin-2-HP-β-CD-complex-CMs exhibited maximum release in simulated colonic fluid (SCF, pH ∼7.0-8.0, almond emulsion-β-glucosidase) with improved therapeutic index in HT-29 cells. Consistently, curcumin-2-HP-β-CD-complex-CMs successively enhanced the colonic bio-distribution of curcumin by ∼8.36 folds as compared to curcumin suspension in preclinical pharmacokinetic studies. In conclusion, curcumin-2-HP-β-CD-complex-CMs warrant further in vivo tumor regression study to establish its therapeutic efficacy in experimental colon cancer., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Reduced brominated derivative of noscapine (Red-Br-Nos, EM012), has potent anti-inflammatory property. However, physicochemical limitations of Red-Br-Nos like low aqueous solubility (0.43×10(-3) g/mL), high lipophilicity (logP∼2.94) and ionization at acidic pH greatly encumber the scale-up of oral drug delivery systems for the management of colitis. Therefore, in present investigation, chitosan microspheres bearing Red-Br-Nos (CTS-MS-Red-Br-Nos) were prepared by emulsion polymerization method and later coated with wheat germ agglutinin (WGA-CTS-MS-Red-Br-Nos) to boost the bioadhesive property. The mean particle size and zeta-potential of CTS-MS-Red-Br-Nos were measured to be 10.5±5.4 μm and 8.1±2.2 mV, significantly (P<0.05) lesser than, 30.2±3.2 μm and 19.2±2.3 mV of WGA-CTS-MS-Red-Br-Nos. Furthermore, various spectral techniques like SEM, FT-IR, DSC and PXRD substantiated that Red-Br-Nos was molecularly dispersed in tailored microspheres in amorphous state. Surface bioadhesive property of WGA-CTS-MS-Red-Br-Nos promoted the affinity toward colon mucin cells in simulated colonic fluid (SCF, pH∼7.2). In vitro release studies carried out on WGA-CTS-MS-Red-Br-Nos and CTS-MS-Red-Br-Nos indicated that SCF with colitis milieu (pH∼4.7) favored the controlled release of Red-Br-Nos, owing to solubilization at acidic pH. Consistently, in vivo investigation also demonstrated the utility of WGA-CTS-MS-Red-Br-Nos, which remarkably attenuated the DSS encouraged neutrophil infiltration, myeloperoxidase activity, and pro-inflammatory cytokine production in C57BL6J mice, as compared to CTS-MS-Red-Br-Nos and Red-Br-Nos suspension. The noteworthy anti-inflammatory activity of WGA-CTS-MS-Red-Br-Nos against acute colitis may be attributed to enhanced drug delivery, affinity and utmost drug exposure at inflamed mucosal layers of colon. In conclusion, WGA-CTS-MS-Red-Br-Nos warrants further in-depth in vitro and in vivo investigations to scale-up the technology for clinical translation., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Leucine-enkephalin (Leu-Enk) is a neurotransmitter or neuromodulator in pain transmission. Due to non-addictive opioid analgesic activity of this peptide, it might have great potential in pain management. Leu-Enk loaded N-trimethyl chitosan (TMC) nanoparticles were prepared and evaluated as a brain delivery vehicle via nasal route. TMC biopolymer was synthesized and analyzed by (1)H NMR spectroscopy. TMC nanoparticles were prepared by ionic gelation method. Mean peptide encapsulation efficiency and loading capacity were 78.28±3.8% and 14±1.3%, respectively. Mean particle size, polydispersity index and zeta potential were found to be 443±23 nm, 0.317±0.17 and +15±2 mV respectively for optimized formulations. Apparent permeability coefficient (Papp) of Leu-Enk released from nanoparticles across the porcine nasal mucosa was determined to be 7.45±0.30×10(-6) cm s(-1). Permeability of Leu-Enk released from nanoparticles was 35 fold improved from the nasal mucosa as compared to Leu-Enk solution. Fluorescent microscopy of brain sections of mice showed higher accumulation of fluorescent marker NBD-F labelled Leu-Enk, when administered nasally by TMC nanoparticles, while low brain uptake of marker solution was observed. Furthermore, enhancement in brain uptake resulted into significant improvement in the observed antinociceptive effect of Leu-Enk as evidenced by hot plate and acetic acid induced writhing assay., (Copyright © 2013 Elsevier B.V. All rights reserved.)