Cationic liposomes with DNA-transportation properties have attracted considerable attention for their ability to deliver medicinal oligonucleotides to mammalian cells. Amongst these are metalloliposomes that use transition metal ions to confer the lipid molecules cationic charge and unique advantages such as redox- and ligand-exchange triggered DNA-release properties. In this study, lipophilic copper (II) and zinc (II) complexes of 1-alkyl-1,4,7-triazacyclononane were prepared to investigate their ability to bind and transfect double stranded DNA with mammalian cells in vitro and in vivo. The copper(II)-surfactant complexes Cu(TACN-C8)2 (1), Cu(TACN-C10)2 (2), Cu(TACN-C12)2 (3), Cu(TACN-C14)2 (4), Cu(TACN-C16)2 (5), and Cu(TACN-C18)2 (6) that comprise ligands that vary in the length of the alkyl group and the zinc (II)-surfactant complex of Zn(TACN-C12)2 (7) were synthesized. The critical micelle concentration (CMC) for 1-7 was measured using fluorescence spectroscopy and an evaluation of the transfection efficiency of the complexes was assessed using the pEGFP-N1 plasmid and HEK 293-T cells. An inverse relationship between DNA transfection efficiency and CMC of the Cu(II) metallosurfactants was observed. The highest transfection efficiency of 38&#x25; was observed for Cu(TACN-C12)2 corresponding to the surfactant with dodecyl alkyl chain having a CMC of 50 &#x3bc;M. Further, an in vivo experiment using mice models was conducted to test the Cu(TACN-C12)2 (3) and Zn(TACN-C12)2 (7) metallosurfactants delivering a DNA vaccine designed for protection against leishmaniasis disease and the study revealed that the Cu-lipoplex elicited the production of significantly more T cells than the Zn-lipoplex and the control group in vivo.

Itizia Z. Arroyo

Clarissa Gomez

Hugo Alarcon

Araceli Jimenez

Andrew Pardo

Gabriel Monta&#xf1;o

Rodrigo X. Armijos

Juan C. Noveron

Alkyl Length Effects on the DNA Transport Properties of Cu (II) and Zn(II) Metallovesicles: An In Vitro and In Vivo Study

The potential of cocoa pod husk (CPH) pectin-based modified release (MR) capsules as a carrier for chronodelivery of hydrocortisone in Sprague-Dawley rats was assessed. Extemporaneously formulated CPH pectin-based hydrocortisone (10 mg) capsules crosslinked with calcium chloride (Formulation A) or zinc (Formulation B) and a commercial immediate release hydrocortisone formulation were administered orally to Sprague-Dawley rats and the pharmacokinetic parameters were evaluated using noncompartmental analysis. Formulation A had a 2 h lag phase followed by an increase in serum drug concentration in the treated rats. Peak concentrations (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.2957pt" id="M1" height="12.0621pt" version="1.1" viewBox="-0.0498162 -8.7664 25.3694 12.0621" width="25.3694pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g121-65" d="M614 175C564 76 510 21 408 21C256 21 146 149 146 336C146 488 235 629 402 629C510 629 570 586 597 480L626 488C620 541 614 582 606 638C578 643 510 665 429 665C206 665 44 527 44 316C44 157 153 -15 402 -15C474 -15 558 5 586 11C604 45 629 119 643 165L614 175Z"/></g><g transform="matrix(.0091,0,0,-0.0091,8.645,3.132)"><path id="g58-107" d="M810 0V30C751 35 744 40 744 106V296C744 396 694 451 614 451C583 451 558 438 537 425C512 409 485 391 454 368C434 420 390 451 342 451C309 451 285 439 260 424C228 405 206 387 185 372V453C141 434 90 421 43 413V386C102 378 105 373 105 309V106C105 41 96 35 29 30V0H243V30C194 35 185 41 185 106V335C216 360 256 389 297 389C357 389 384 348 384 275V106C384 41 374 35 312 30V0H530V30C475 35 465 41 465 104V294C465 313 464 324 463 336C502 367 539 389 576 389C637 389 663 346 663 274V109C663 41 653 35 593 30V0H810Z"/></g><g transform="matrix(.0091,0,0,-0.0091,16.207,3.132)"><path id="g58-95" d="M442 39L431 68C420 63 406 57 394 57C377 57 359 71 359 118V301C359 353 349 393 314 424C291 443 261 451 230 451C171 438 107 401 79 381C59 366 46 355 46 340C46 316 72 295 91 295C106 295 117 303 122 319C131 350 139 371 152 384C163 397 178 404 197 404C246 404 281 365 281 293V278C260 262 186 232 124 213C69 194 41 161 41 112C41 47 92 -12 163 -12C195 -12 243 25 283 51C288 35 293 22 308 7C319 -4 339 -12 354 -12L442 39ZM281 87C262 68 226 51 199 51C169 51 129 74 129 126C129 162 151 181 190 198C211 208 259 229 281 240V87Z"/></g><g transform="matrix(.0091,0,0,-0.0091,20.293,3.132)"><path id="g58-118" d="M482 0V30C420 38 407 48 370 103L273 248C308 299 331 332 352 357C387 397 401 404 463 409V439H277V409C318 405 324 400 307 369C290 337 270 307 251 279L194 367C175 396 180 402 220 409V439H18V409C74 401 87 395 117 349L204 213C173 168 147 130 119 95C78 46 67 38 5 30V0H195V30C144 38 143 47 162 79C181 112 202 149 225 181L297 70C314 43 307 35 264 30V0H482Z"/></g></svg>) of 21.799 ± 1.993 ng/ml and 20.844 ± 2.661 ng/ml were achieved after 6 ± 0.23 h and 6 ± 0.35 h (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.2957pt" id="M2" height="12.0621pt" version="1.1" viewBox="-0.0498162 -8.7664 24.7431 12.0621" width="24.7431pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g121-82" d="M592 498C586 556 582 629 581 675H560C545 656 537 650 510 650H115C87 650 74 652 60 675H40C38 620 33 555 28 495H57C69 539 77 568 89 585C102 607 122 616 205 616H267V123C267 44 259 34 168 28V0H454V28C360 34 352 44 352 123V616H422C498 616 514 608 531 584C542 568 552 543 562 495L592 498Z"/></g><g transform="matrix(.0091,0,0,-0.0091,8.021,3.132)"><use xlink:href="#g58-107"/></g><g transform="matrix(.0091,0,0,-0.0091,15.583,3.132)"><use xlink:href="#g58-95"/></g><g transform="matrix(.0091,0,0,-0.0091,19.669,3.132)"><use xlink:href="#g58-118"/></g></svg>), respectively, for capsules A and B. The immediate release formulation had a peak concentration of 15.322 ± 0.313 ng/ml within 1 ± 0.2 h. The relative bioavailability of the CPH pectin-based capsules A and B was 213% and 274%, respectively. Formulations A and B had half-lives more than three times that of the immediate release formulation. The MR capsules exhibited a higher exposure, greater bioavailability, and versatility in release of cortisol than the commercial immediate release formulation. Additionally, the MR capsules exhibited an extended drug release with overnight cortisol rise and early morning cortisol peak and hold promise in the management of adrenal insufficiency.

Ofosua Adi-Dako

Kwabena Ofori-Kwakye

Seth Kwabena Amponsah

Isaac Boamah

Noble Kuntworbe

Esther Eshun Oppong

Potential of Cocoa Pod Husk Pectin-Based Modified Release Capsules as a Carrier for Chronodelivery of Hydrocortisone in Sprague-Dawley Rats

Treatment for herpes simplex virus-1 and -2 (HSV-1 and -2) patients who suffer from recurrent outbreaks consists of multiple daily doses of the antiviral drugs acyclovir (ACV), penciclovir, or their more orally bioavailable derivatives valacyclovir or famciclovir. Drug troughs caused by missed doses may result in viral replication, which can generate drug-resistant mutants along with clinical sequelae. We developed a molecularly homogeneous mixture of ACV with the bioerodable polymer polycaprolactone. Through scanning electron microscopy, infrared spectroscopy, gel permeation chromatography, 1H NMR, and differential scanning calorimetry, our method of combining drug and polymer, termed Volatile Acid-Solvent Evaporation (VASE), does not compromise the integrity of polymer or drug. Furthermore, VASE creates materials that deliver therapeutic amounts of drug consistently for approximately two months. Devices with high enough drug loads diminish primary infection of HSV-1 in Vero cells to the same level as seen with a single dose of ACV. Our data will lead to further experiments in animal models, demonstrating efficacy in preventing reactivation of these viruses with a single intervention, and with other antiviral drugs amenable to such manipulation. Additionally, this type of treatment would leave no trace after its useful lifetime, as drug is released and polymer matrix is degraded in vivo.

James R. Stegman

Jill K. Badin

Kaitlyn A. Biles

Thamar Etienne

Sogand Fartash-Naini

Ariel D. Gordon

Zachary W. Greeley

Benjamin W. Harding

Ricardo J. Mack

Danielle Masica

Ashley N. Nelson

Amandeep K. Samra

Sarah E. Smith

Gabrielle P. Thomas

Haley J. Zack

Timothy J. Brunker

Barry J. Margulies

Volatile Acid-Solvent Evaporation (VASE): Molecularly Homogeneous Distribution of Acyclovir in a Bioerodable Polymer Matrix for Long-Term Treatment of Herpes Simplex Virus-1 Infections

In alternate systems of medicine like Ayurveda and traditional Chinese medicine, Hibiscus rosa sinensis and its extracts have been traditionally prescribed for their antidepressant activity. Crude extracts and rudimentary formulations approaches are good for proof-of-concept studies; however, these formulations are fraught with problems like poor oral bioavailability and high variability between subjects. Systematic drug delivery approaches could prove effective in addressing some of these problems. In this study, we report the development of Hibiscus rosa sinensis extract loaded solid lipid nanoparticles (HSLNs) using glycerol monostearate or beeswax as lipids. The HSLNs were evaluated for their size, surface charge, and morphology. The optimized HSLNs were tested for antidepressant activity in male Swiss albino mice. It was found that, with the optimized procedure, HSLNs of &#x7e;175 nm, carrying negative charge and nearly spherical shape, could be obtained. The in vivo test results suggested that there were marked differences in the immobility times of the test animals. Moreover, with HSLNs, it was found that at doses several times lower than the native crude extract dose, similar pharmacological effect could be obtained. These initial findings suggest that encapsulating phytopharmaceuticals into advanced delivery systems like solid lipid nanoparticles can be an effective strategy in improving their in vivo performance.

P. Vijayanand

V. Jyothi

N. Aditya

A. Mounika

Development and Characterization of Solid Lipid Nanoparticles Containing Herbal Extract: In Vivo Antidepressant Activity

Antimicrobial study of biofunctionalized silver nanoparticles has been done with the emphasis on its mechanism on both gram positive and negative bacteria. The biofunctionalized silver nanoparticles are employed considering their importance in green chemistry with respect to easy synthesis, usefulness, and economic synthetic procedure involved. The stability of these nanoparticles was determined by zeta potential analyzer. The probable mechanism of antibacterial activity was performed on Proteus mirabilis by field emission scanning electron microscopy (FESEM) and energy dispersive spectroscopy (EDAX) study which does not show the presence of silver. The free radicals generated by silver nanoparticles were responsible for lethal antibacterial activity by rupturing the cell surface which causes improper nutrient and signal supply. Free radical scavenging efficacy of silver nanoparticles was confirmed by 1,1-Diphenyl-2-picrylhydrazyl (DPPH) method. AgNP enhanced the membrane leakage of reducing sugars by destroying the proteins existing on the cell wall. These nanoparticles are found to be toxic against human pathogens and are highly effective on Staphylococcus aureus. The effect of silver nanoparticles is concentration dependent and independent of the type of strains used.

Asra Parveen

Manjunath S. Yalagatti

Venkataraman Abbaraju

Raghunandan Deshpande

Emphasized Mechanistic Antimicrobial Study of Biofunctionalized Silver Nanoparticles on Model Proteus mirabilis

Background. Artesunate is one of the most potent, rapidly acting and therapeutically versatile antimalarial drugs. Its efficacy is hampered by poor aqueous solubility and stability resulting in low oral bioavailability. Recent efforts to nanoformulate artesunate have shown great potential of improving its dissolution profile and bioavailability. However, no study has yet been done to investigate the intestinal permeability of these nanoformulations, which is a critical determinant of systemic absorption. Objective of the Study. The main aim of the study was to determine the intestinal permeability of artesunate-loaded solid lipid nanoparticles (SLN). Method. The microemulsion dilution technique was used to fabricate artesunate-loaded solid lipid nanoparticles. In vitro drug release studies were performed at pH 1.2 and 6.8 using the dialysis membrane method. The everted gut sac method was used to assess the intestinal permeability of the prepared nanoparticles. Results. The average particle size was 1109 nm and the polydispersity index (PDI) was 0.082. The zeta potential was found to be −20.7 mV. The encapsulation efficiency of the solid lipid nanoparticles obtained was 51.7%. At both pH 1.2 and 6.8, pure artesunate was rapidly released within the first 30 mins while the SLN showed a biphasic release pattern with an initial burst release during the first hour followed by a prolonged release over time. The rate of drug release increased with increasing pH. The apparent permeability (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-5.3006pt" id="M1" height="13.9365pt" version="1.1" viewBox="-0.0498162 -8.6359 20.8702 13.9365" width="20.8702pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.0091,0,0,-0.0091,6.656,3.132)"><path id="g58-95" d="M442 39L431 68C420 63 406 57 394 57C377 57 359 71 359 118V301C359 353 349 393 314 424C291 443 261 451 230 451C171 438 107 401 79 381C59 366 46 355 46 340C46 316 72 295 91 295C106 295 117 303 122 319C131 350 139 371 152 384C163 397 178 404 197 404C246 404 281 365 281 293V278C260 262 186 232 124 213C69 194 41 161 41 112C41 47 92 -12 163 -12C195 -12 243 25 283 51C288 35 293 22 308 7C319 -4 339 -12 354 -12L442 39ZM281 87C262 68 226 51 199 51C169 51 129 74 129 126C129 162 151 181 190 198C211 208 259 229 281 240V87Z"/></g><g transform="matrix(.0091,0,0,-0.0091,10.578,3.132)"><path id="g58-110" d="M173 382V461C125 442 68 425 25 418V390C88 382 92 382 92 317V-127C92 -191 84 -199 18 -204V-235H259V-204C180 -196 173 -192 173 -120V7C188 -1 212 -11 243 -12C375 12 495 109 495 261C495 361 427 451 316 451C303 451 283 446 266 435L173 382ZM173 345C200 365 243 388 274 388C346 388 409 329 409 222C409 111 353 40 266 40C231 40 196 56 173 79V345Z"/></g><g transform="matrix(.0091,0,0,-0.0091,15.336,3.132)"><use xlink:href="#g58-110"/></g></svg>) of SLN was found to be greater (0.169 mg/cm2) as compared to that of pure artesunate (0.117 mg/cm2) at the end of the experiment. Conclusion. The results obtained in this study showed that the microemulsion dilution technique can be used to formulate artesunate solid lipid nanoparticles. The formulation exhibited a sustained drug release profile. The intestinal permeability of artesunate could be enhanced by the nanoformulation.

Wadzanayi L. Masiiwa

Louis L. Gadaga

Intestinal Permeability of Artesunate-Loaded Solid Lipid Nanoparticles Using the Everted Gut Method

Inhalation therapy has strong history of more than 4000 years and it is well recognized around the globe within every culture. In early days, inhalation therapy was designed for treatment of local disorders such as asthma and other pulmonary diseases. Almost all inhalation products composed a simple formulation of a carrier, usually &#x3b1;-lactose monohydrate orderly mixed with micronized therapeutic agent. Most of these formulations lacked satisfactory pulmonary deposition and dispersion. Thus, various alternative carrier&#x2019;s molecules and powder processing techniques are increasingly investigated to achieve suitable aerodynamic performance. In view of this fact, more suitable and economic alternative carrier&#x2019;s molecules with advanced formulation strategies are discussed in the present review. Furthermore, major advances, challenges, and the future perspective are discussed.

Piyush Mehta

Imagine the Superiority of Dry Powder Inhalers from Carrier Engineering

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Journal of Drug Delivery publishes papers on all aspects of therapeutic delivery and targeting, ranging from basic biology of drug and gene delivery through to application and development of these principles.

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Journal of Drug Delivery - Table of contents 2018

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Journal of Drug Delivery ceased publication in 2019 and is no longer accepting submissions.

description

Journal of Drug Delivery publishes papers on all aspects of therapeutic delivery and targeting, ranging from basic biology of drug and gene delivery through to application and development of these principles.

Journal of Drug Delivery