3 research outputs found
Ultrasensitive Phototriggered Local Anesthesia
An injectable local anesthetic producing
repeatable on-demand nerve
block would be desirable for pain management. Here we present a phototriggerable
device to achieve repeatable and adjustable on-demand local anesthesia
in superficial or deep tissues, consisting of gold nanorods attached
to low temperature sensitive liposomes (LTSL). The particles were
loaded with tetrodotoxin and dexmedetomidine. Near-infrared light
(NIR, 808 nm, continuous wave) could heat gold nanorods at low fluence
(short duration and low irradiance), leading to rapid release of payload.
In vivo, 1–2 min of irradiation at ≤272 mW/cm<sup>2</sup> produced repeatable and adjustable on-demand infiltration anesthesia
or sciatic nerve blockade with minimal toxicity. The nerve block intensity
and duration correlated with the irradiance and duration of the applied
light
Phototriggered Local Anesthesia
We report a phototriggerable formulation
enabling <i>in vivo</i> repeated and on-demand anesthesia
with minimal toxicity. Gold nanorods (GNRs) that can convert near-infrared
(NIR) light into heat were attached to liposomes (Lip-GNRs), enabling
light-triggered phase transition of their lipid bilayers with a consequent
release of payload. Lip-GNRs containing the site 1 sodium channel
blocker tetrodotoxin and the α<sub>2</sub>-adrenergic agonist
dexmedetomidine (Lip-GNR-TD) were injected subcutaneously in the rat
footpad. Irradiation with an 808 nm continuous wave NIR laser produced
on-demand and repeated infiltration anesthesia in the rat footpad
in proportion to the irradiance, with minimal toxicity. The ability
to achieve on-demand and repeated local anesthesia could be very beneficial
in the management of pain
Extended Release of Native Drug Conjugated in Polyketal Microparticles
Polyketals, which can be biodegradable,
have good biocompatibility,
and are pH-sensitive, could have broad applicability in drug delivery
and other biomedical applications. However, facile synthesis of high
molecular weight polyketals is challenging, and short durations of
drug release from polyketal particulate formulations limit their application
in drug delivery. Here we report the synthesis of a di-isopropenyl
ether monomer and its use to synthesize high molecular weight estradiol-polyketal
conjugates by addition polymerization. Microparticles were prepared
from the estradiol-polyketal conjugate, where estradiol was incorporated
into the polymer backbone. The particles had high drug loading and
significantly prolonged drug release. Release of estradiol from the
drug-polyketal conjugate microparticles was acid-responsive, as evidenced
by faster drug release at low pH and with co-incorporation of PLGA.
Tissue reaction to the microparticles was benign <i>in vivo</i>. Polyketal drug conjugates are promising candidates for long-acting
drug delivery systems to treat chronic diseases